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Many cancer patients use integrative therapies with a combination of natural products and diets. In the Western world, integrative medicine is often not shared with oncologists even during antineoplastic treatments. This behavior stems from the unmet needs of cancer patients who may feel oncologists’ underestimation of their symptoms and spiritual aspects. This case report demonstrates the potential harm of inadequate diet and nutraceutical intake in a 68-year-old woman with metastatic estrogen receptor-positive, human epidermal growth factor receptor-2-negative breast cancer. Her care team recommended hormone therapy with abemaciclib plus fulvestrant. Her diarrhea started after 10 days of therapy and did not disappear, despite the use of loperamide, causing a significant reduction in adherence and dose intensity of abemaciclib. The patient finally disclosed to her oncologist she was following a detoxifying diet and taking several nutraceuticals. Her diarrhea was correlated with abemaciclib but most probably exacerbated and prolonged by the diet. Evaluation of disease after 3 months showed progressive disease. Integrative medicine should be in the multidisciplinary management of cancer patients to avoid potentially harmful events and ameliorate patients’ quality of life in a holistic approach.

To date, the virtual multidisciplinary tumor boards (vMTBs) are increasingly used to achieve high-quality treatment recommendations across health-care regions, which expands and develops the local MTB team to a regional or national expert network. This review describes the process of lung cancer-specific MTBs and the transition process from face-to-face tumor boards to virtual ones. The review also focuses on the project organization's description, advantages, and disadvantages. Semi-structured interviews identified five major themes for MTBs: current practice, attitudes, enablers, barriers, and benefits for the MTB. MTB teams exhibited positive responses to modeled data feedback. Virtualization reduces time spent for travel, allowing easier and timely patient discussions. This process requires a secure web platform to assure the respect of patients’ privacy and presents the same unanswered problems. The implementation of vMTB also permits the implementation of networks especially in areas with geographical barriers facilitating interaction between large referral cancer centers and tertiary or community hospitals as well as easier access to clinical trial opportunities. Studies aimed to improve preparations, structure, and conduct of MTBs, research methods to monitor their performance, teamwork, and outcomes are also outlined in this article. Analysis of literature shows that MTB participants discuss 5–8 cases per meeting and that the use of a vMTB for lung cancer and in particular stage III NSCLC and complex stage IV cases is widely accepted by most health professionals.Despite still-existing gaps, overall vMTB represents a unique opportunity to optimize patient management in apatient-centeredapproach.

Background Chemotherapy-induced neutropenia (CIN) has been demonstrated to be a prognostic factor in several cancer conditions. We previously found a significant prognostic value of CIN on overall survival (OS), in a pooled dataset of patients with advanced non-small-cell lung cancer (NSCLC) receiving first line chemotherapy from 1996 to 2001. However, the prognostic role of CIN in NSCLC is still debated. Methods We performed a post hoc analysis pooling data prospectively collected in six randomized phase 3 trials in NSCLC conducted from 2002 to 2016. Patients who never started chemotherapy and those for whom toxicity data were missing were excluded. Neutropenia was categorized on the basis of worst grade during chemotherapy: absent (grade 0), mild (grade 1–2), or severe (grade 3–4). The primary endpoint was OS. Multivariable Cox model was applied for statistical analyses. In the primary analysis, a minimum time (landmark) at 180 days from randomization was applied in order to minimize the time-dependent bias. Results Overall, 1529 patients, who received chemotherapy, were eligible; 572 of them (who received 6 cycles of treatment) represented the landmark population. Severe CIN was reported in 143 (25.0%) patients and mild CIN in 135 (23.6%). At multivariable OS analysis, CIN was significantly predictive of prognosis although its prognostic value was entirely driven by severe CIN (hazard ratio [HR] of death 0.71; 95%CI: 0.53–0.95) while it was not evident with mild CIN (HR 1.21; 95%CI: 0.92–1.58). Consistent results were observed in the out-of-landmark group (including 957 patients), where both severe and mild CIN were significantly associated with a reduced risk of death. Conclusion The pooled analysis of six large trials of NSCLC treatment shows that CIN occurrence is significantly associated with a longer overall survival, particularly in patients developing severe CIN, confirming our previous findings.

Introduction: Large and consistent evidence supports the use of eribulin mesylate in clinical practice in third or later line treatment of metastatic triple negative breast cancer (mTNBC). Conversely, there is paucity of data on eribulin efficacy in second line treatment. Methods: We investigated outcomes of 44 mTNBC patients treated from 2013 through 2019 with second line eribulin mesylate in a multicentre retrospective study involving 14 Italian oncologic centres. Results: Median age was 51 years, with 11.4% of these patients being metastatic at diagnosis. Median overall survival (OS) and progression free survival (PFS) from eribulin starting were 11.9 (95%CI: 8.4-15.5) and 3.5 months (95%CI: 1.7-5.3), respectively. We observed 8 (18.2%) partial responses and 10 (22.7%) patients had stable disease as best response. A longer PFS on previous first line treatment predicted a better OS (HR=0.87, 95%CI: 0.77-0.99, p= 0.038) and a longer PFS on eribulin treatment (HR=0.92, 95%CI: 0.85-0.98, p=0.018). Progression free survival to eribulin was also favorably influenced by prior adjuvant chemotherapy (HR=0.44, 95%CI: 0.22-0.88, p=0.02). Eribulin was generally well tolerated, with grade 3-4 adverse events being recorded in 15.9% of patients. Conclusions: The outcomes described for our cohort are consistent with those reported in the pivotal Study301 and subsequent observational studies. Further data from adequately-sized, ad hoc trials on eribulin use in second line for mTNBC are warranted to confirm our findings.

Background/aim Upper limb breast cancer-related lymphedema (BCRL) is a chronic and severe condition affecting a significant percentage of breast cancer survivors. Even though its physiopathology is well-known, there is no worldwide consensus on BCRL evaluation and a gold-standard treatment. This narrative review aims at providing a brief descriptive overview with regard to BCRL treatment modalities. Materials and methods We conducted a literature search within the PubMed database, and 33 articles out of 56 were selected, including reviews, systematic reviews, and meta-analyses aiming find the most updated evidence regarding BCRL treatment modalities. Results Physical exercise (aerobic exercise, resistance exercise, aquatic therapy), bandages, and intermittent pneumatic compression were shown to be most effective in BCRL patients, in terms of swelling reduction in the acute-intensive phase. Furthermore, physical exercise was beneficial also as a maintenance tool. Manual lymphatic drainage demonstrated efficacy in preventing secondary lymphedema if applied immediately after breast cancer surgery or in early phases of BCRL or as a maintenance tool. Complementary procedures such as acupuncture, reflexology, yoga and photo-biomodulation therapy did not show conclusive results in BCRL treatment. Surgery was shown effective in managing symptoms (liposuction), preventing (lymphaticovenular anastomosis) and treating BCRL (vascularized lymph node transfer). Conclusion BCRL is still a challenging condition either for breast cancer survivors and clinicians, deeply impacting patient functioning and quality of life. Due to the lack of globally accepted criteria in evaluating BCRL, to date a gold standard treatment for this widespread issue is still needed.

Simple Summary Community care activity in the oncology field does not exist. This unmet need contrasts with the increasing number of patients with a previous diagnosis of cancer. Abstract Over the last few decades, thanks to early detection, effective drugs, and personalized treatments, the natural history of cancer has radically changed. Thanks to these advances, we have observed how survival of cancer patients has increased, becoming an ever more important goal in cancer care. Effective clinical governance of survivorship care is essential to ensure a successful transition between active and post-treatment life, identifying optimization of healthcare outcomes and quality of life for patients as the primary objectives. For these reasons, potential intervention models must consider these differences to rationalize the available resources, including economic aspects. In this perspective, analyzing the different models proposed in the literature to manage this type of patients, we focus on the possible role of the so-called “community oncologist”. As a trained health professional, also focused on longevity, he could represent the right management solution in all those “intermediate” clinical conditions that arise between the hospital specialist, frequently overworked, and the general practitioner, often biased by the lack of specific expertise.

A retrospective analysis of 70 patients with triple-negative or hormone-resistant advanced breast carcinoma who had not previously received chemotherapy was carried out. Patients received oral vinorelbine 60 mg/m2 on day 1 and 8, plus capecitabine 1000 mg/m2 bid for 14 consecutive days every 3 weeks. Overall response rate was 53% with a 9% complete response rate. Stable disease was recorded in 27% of the cases. Median progression-free survival was 7.9 months and median overall survival was 29.2 months. Toxicity was generally mild and easily manageable. These data demonstrate that this combination is feasible, safe and active as first-line treatment of triple-negative fully hormone-resistant advanced breast carcinoma patients., Lay abstract The adoption of metronomic chemotherapy in the treatment of breast cancer is an important step forward in the management of this disease. The fluoropyrimidine capecitabine and the vinca alkaloid vinorelbine have been shown to be at least as active. Our data confirm the activity and safety of this all-oral regimen as first-line metronomic therapy being response rate.

Purpose Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting. Methods We used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%). Results Overall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9–7.2) and 12.1 months (95% CI: 9.6–16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0–18.4), 6.1 months (95% CI: 4.0–8.9) for CTX-based and 5.3 months (95% CI: 4.1–9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3–16.7 and CTX-based ones (95%CI: 8.7–52.8). Tumour response, PFS and OS decreased proportionally in later lines. Conclusion This analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.

Objective Eribulin mesylate (EM) is a fully synthetic macrocyclic ketone analogue of the marine natural product halichondrin. EM has been reported to be active in metastatic breast cancer. In this paper, we report efficacy and safety of data of EM in a retrospective, real-world series of patients with poor prognosis, hormone-refractory, or triple-negative metastatic breast cancer. Materials and methods The analysis was carried out at 4 interrelated oncology centers. EM was delivered at the dose of 1.4 mg/m2 in 100 mL of normal saline over 2 to 5 minutes on days 1 and 8 every 21 days. EM was continued until disease progression or unacceptable toxicity. Side effects were reported every cycle as per standard clinical practice and graded according to NCI-CTCAE, version 4.0. Time-to-progression and overall survival were reported. Results In this series of 90 patients the overall response rate was 22%, and 21% and 23% in the hormonal-resistant group and the triple-negative one, respectively. Stable disease was recorded in 24%, 21%, and 27%, respectively, in the whole series, the hormonal-resistant group, and the triple-negative one, respectively. Time-to-progression was 3.5 months (range, 1 to 22 mo) in the whole series and 3.0 months (range, 1 to 14.7 mo) and 3.4 months (range, 2.2 to 16.2 mo) in the hormonal-resistant group and the triple-negative one, respectively. Overall survival reached a median of 11.4 months. Conclusions This multicenter study, albeit retrospective, demonstrates the activity of this combination as third-line chemotherapy option in a challenging clinical setting such as triple-negative or hormone-resistant patients with breast cancer progressing after several lines of hormonal manipulations.

Introduction: The discovery and the clinical availability of novel cyclin-dependent kinases 4 and 6 inhibitors have profoundly changed the therapeutic scenario of metastatic hormone receptor-positive breast carcinoma. Among these inhibitors, abemaciclib can induce potent and sustained cell cycle arrest and immune system stimulation. Areas covered: This review summarizes the safety profile and clinical efficacy data on abemaciclib alone or in combination with aromatase inhibitors or fulvestrant in metastatic hormone receptor-positive breast carcinoma. The management of patients treated with abemaciclib is the object of this paper. Expert opinion: As shown in phase 2 and 3 clinical trials on efficacy and tolerability, abemaciclib is a potentially convenient, safe, and effective agent for the treatment of patients with advanced hormone receptor-positive patients. Orally administered abemaciclib in combination with aromatase inhibitors or fulvestrant has the potential to allow significant improvement in survival outcomes, quality of life, response rate, and duration of response even in poor prognosis subgroups. Adequate patients’ information, clinical selection, and prompt, proactive management of side effects are mandatory.

Aim This paper aims to analyze the usefulness of the G8 geriatric oncology questionnaire in patients with advanced/metastatic pancreatic adenocarcinoma (aPAC) and its possible association with different clinical outcomes. Methods Patients age > 70 years were screened with the G8 tool and treated with intravenous nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 for 3 consecutive weeks followed by one-week rest as prescribed after clinical evaluation by treating oncologists. Patient’s charts were evaluated for type and severity of toxicity, 2 cycle rate of completion, discontinuation rate, delays, dose reductions, and other outcomes response rates, progression-free, and overall survival. Sensitivity, specificity, and possible correlations were analyzed. Results Sensitivity and specificity of the G8 score for severe toxicity were respectively 55.9% and 50%. No association between all types of severe grade 3-4 toxicity, delays, or dose reductions, and the G8 score was present (p=0.622). ORR was 32.5% with no complete responses. Median PFS and OS were 4.5 months and 8.1 months, respectively. Correlation between G8 score and PFS was not statistically significant (p=0.0652). Correlation between G8 score and OS was statistically significant (p=0.0251). Although median survival of G8 fit patients was superior to that of G8 vulnerable patients (6.5 versus 4 months), the difference was not statistically different (p=0.1975). Conclusion Clinical results in terms of response rate, survival outcomes, and side-effects were in the range reported by others. However, the G8 questionnaire is not a reliable diagnostic tool to predict the risk of severe toxicity, and clinical outcomes in older patients with aPAC.

PURPOSE This descriptive investigation was undertaken at three oncology units to report queries, needs, and fears related to severe acute respiratory syndrome coronavirus 2 (COVID-19) of patients with cancer and to avoid uncontrolled treatment delays or withdrawal, behavioral mistakes, and panic. PATIENTS AND METHODS All queries spontaneously delivered through the WhatsApp instant messaging system commonly used by patients to communicate with oncology units were collected and grouped by homology in five categories. Responses to the queries were given according to recommendations by the Italian Association of Medical Oncology through WhatsApp and by subsequent phone calls. Patients were also classified according to the site of the primary tumor, stage of disease, and current treatments. Analysis of the association between these data and queries was carried out. RESULTS The social scenario in Italy is a nationwide lockdown except for hospitals, pharmacies, and food supplies. Overall, 446 different patients’ WhatsApp conversations were analyzed between March 1 and March 13 and comprised the following: requirement of visit delay by patients undergoing oral therapies or in follow-up, delays in chemotherapy or immunotherapy administration, queries about possible immunosuppression, and changes in lifestyle or daily activities. Delay requirements were statistically more frequent among patients with prostate or breast cancer compared with those with lung or pancreatic cancer. Actions taken by oncologists are also reported. CONCLUSION To our knowledge, the WhatsApp instant messaging system has been occasionally used in other medical settings with controversial results. In our experience, WhatsApp turned out to be adequate to give a rapid answer to most queries from patients with cancer in the COVID-19 pandemic scenario.

Purpose The availability of immune checkpoint inhibitors has deeply changed the therapeutic scenario of patients with advanced non-small cell lung cancer (NSCLC). Up until now, chemotherapy still represents the first-line treatment for patients with advanced NSCLC not harbouring genetic mutations or lacking high expression of programmed death ligand even if the addition of immunotherapy to first-line chemotherapy has recently been shown to improve clinical outcome. We carried out a multi-institutional retrospective analysis on third-line chemotherapy with metronomic oral vinorelbine (VNR) in a series of patients with metastatic NSCLC pre-treated with first-line chemotherapy and second-line immunotherapy. Patients and methods Thirty patients with metastatic NSCLC with progressive disease after first-line chemotherapy and subsequent immunotherapy were treated with metronomic oral VNR continuously at the fixed dose of 30 mg three times per week. Results A partial response was achieved in 4 patients (13.3%), while 10 patients (33.3%) displayed disease stabilisation for an overall disease control rate of 46.7%. Median progression-free survival was 3.9 months (range 1-13 months) and median OS reached 8.1 months (range 4.0-24.0+ months) with a 12-month survival rate of 22%. Conclusion Oral metronomic VNR appears to be active and safe in patients with metastatic NSCLC in progression after first-line chemotherapy and second-line immunotherapy. The results reported, although from a limited sample, may suggest its use for long-term stabilisation of the disease with good patient compliance.

Aim This retrospective observational study evaluated the role of hypo-fractionated stereotactic radiotherapy (SRT) in patients with oligo-progressive metastatic renal cell carcinoma (mRCC) treated with first-line oral tyrosine kinase inhibitors (TKI). Data on local control, delay of further progression, and safety are reported. Patients and methods Between January 2010 and December 2016, 28 patients with mRCC who showed oligo-progressive disease while receiving first-line pazopanib were treated with hypofractionated SRT to progressive metastatic sites to delay the change of systemic therapy. First and second progression-free survival (PFS-1 and PFS-2) were recorded, as well as objective response and toxicity. Results After pazopanib therapy, nine partial remissions (32%), 12 stable disease (43%) and seven progressions (25%) were recorded. The median time to progression from first-line pazopanib until oligo-progression was 9.45 months (PFS-1 range=2-30 months). Seventeen patients (61%) showed progression at pre-existing tumor sites, and 11 patients (39%) showed the appearance of new metastases. Progression-free survival after radiation therapy was 4.55 months (PFS-2 range=1-11 months). PFS-1 plus PFS-2 was 14.0 months (range=3-41 months). Severe grade 3-4 toxicities were seen only occasionally. Conclusion Patients with oligo-progressive mRCC treated with first-line pazopanib may benefit from hypo-fractionated high-dose SRT at progressing sites achieving a further increase in median progression-free survival. Further studies and prospective validation are required to establish if this minimally invasive approach may have a positive impact on overall survival and reported outcomes.

Fighting cancer is an economically expensive challenge for both health care payers, and the patients and their families and the median costs for cancer care are rapidly increasing in the last decade. Although both direct and indirect costs of medical assistance have been a frequent source of distress and contention, however analysis of the non-medical expenses incurred directly by cancer patients has not received adequate attention. Developing a deeper understanding of so-called "out-of-pocket" costs may be necessary. Out-of-pocket costs for medical care range from 7 % to 11 % of medical costs for all payers. However, the range of out-of-pocket costs shows considerable variability in different studies. In this review, we reviewed available data concerning direct and indirect medical costs, including psychosocial ones.

Objectives Data supporting the prognostic role of chemotherapy induced haematological toxicity suggest that toxicity-adjusted-dosing (TAD) of chemotherapy might improve treatment efficacy. We tested whether TAD of the cisplatin-etoposide combination might improve the response rate, in previously untreated extensive stage disease (ED)-SCLC patients, as compared with standard fixed-dosing (FD). Methods Patients with ED-SCLC were randomized to receive either TAD or FD of cisplatin-etoposide as first-line treatment. Primary endpoint was the objective response rate (ORR) according to the RECIST 1.0 criteria, secondary endpoints included progression free survival (PFS), overall survival (OS) and toxicity. Results Hundred-fifty-eight patients were randomized. Most patients were male, with ECOG-PS 1, without brain metastases and had not received radiotherapy before study entry. Response rate was 54.4 (95%CI: 43.5–64.9%) and 58.2 (95%CI: 47.2–68.5%) in the control and experimental arms, respectively (P = 0.75). No significant differences were found in terms of PFS (HR 1.04; 95%CI: 0.74–1.44, P = 0.84) and OS (HR1.01; 95%CI 0.71–1.42, p = 0.97). Seven patients died on treatment, one in the standard arm and 6 in the experimental arm. The most frequent cause of death was neutropenia with infection and, apart in one, death was not related to dose modification. Severe toxicity was more frequent in the experimental arm (91% vs 60%). Conclusions In our population of chemonaive ED SCLC patients, TAD failed to improve the ORR, PFS and OS over the FD of cisplatin-etoposide as first line chemotherapy and was associated with increased toxicity.

// Lucia Kim 1,12,* , Mauro Saieg 1,13,* , Massimo Di Maio 2,14,* , Ciro Gallo 3,* , Charles Butts 4 , Fortunato Ciardiello 5 , Ronald Feld 6 , Dengxiao Cheng 6 , Vittorio Gebbia 7 , Marco Angelo Burgio 8 , Yasmin Alam 9 , Simona Signoriello 3 , Antonio Rossi 10 , Natasha Leighl 6 , Paolo Maione 10 , Alessandro Morabito 2 , Geoffrey Liu 6,** , Ming-Sound Tsao 1,** , Francesco Perrone 2,** and Cesare Gridelli 10,11,** 1 Department of Pathology, University Health Network, Princess Margaret Cancer Center and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada 2 National Cancer Institute, G. Pascale Foundation, IRCCS, Naples, Italy 3 Department of Mental Health and Preventive Medicine, Chair of Statistics, Second University of Naples, Naples, Italy 4 Medical Oncology, Cross Cancer Institute, Edmonton, Canada 5 Medical Oncology, Second University, Naples, Italy 6 Division of Hematology and Oncology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada 7 Medical Oncology, Casa di Cura La Maddalena, Palermo, Italy 8 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy 9 Medical Oncology, Windsor Regional Cancer Centre, Windsor, Canada 10 Department of Oncology/Hematology, Division of Medical Oncology, “S.G. Moscati” Hospital, Avellino, Italy 11 On behalf of the TORCH Investigators 12 Department of Pathology, Inha University School of Medicine, Incheon, South Korea 13 Santa Casa Medical School, Sao Paulo, SP, Brazil 14 University of Turin, Turin, Italy * Co-first author ** Co-last author Correspondence to: Cesare Gridelli, email: // Keywords : NSCLC, EGFR TKI, biomarker analysis, predictive factors, prognostic factors Received : November 09, 2016 Accepted : February 01, 2017 Published : February 25, 2017 Abstract Background: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. Methods: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting. Progression-free survival (PFS) was the primary end-point, overall survival, response rate and side effects (diarrhoea and skin toxicity) were secondary end-points. Interactions between biomarkers and treatment were studied with multivariable models (either Cox model or logistic regression). Statistical analyses accounted for multiple comparisons. Results: At least one biomarker was assessed in 324 out of 760 patients in the TORCH study. EGFR mutation was more common in female ( P = 0.0001), East Asians ( P < 0.0001) and never smoker ( P < 0.0001) patients; low MET protein expression by IHC (H-score

Background: Agent targeting HER-2 pathway plus chemotherapy has represented a major progress in the management of patients with breast cancer. However, the role of late-line treatment in heavily pretreated patients is still largely unclear. In the last decade, nab-paclitaxel has shown significant activity and good toxicity profile in metastatic breast cancer. Case Presentation: We report the case of a 76-year-old Caucasian woman with metastatic HER-2 positive ductal infiltrating breast carcinoma treated with a combination of weekly nab-paclitaxel and trastuzumab as fifth-line therapy. She had previously received first-line paclitaxel and trastuzumab, second-line vinorelbine and trastuzumab, third-line TDM1 and fourth-line oral capecitabine and lapatinib. Clinical and radiological staging showed progression at bone, skin and soft-tissue. The patient received weekly nab-paclitaxel plus trastuzumab. Massive objective response was clinically and PET documented which lasted 8 months. Tolerance to treatment was fairly good as well as cardiac safety. Conclusion: To the best of our knowledge, this is the first reported case of efficacy of nab-paclitaxel in combination with trastuzumab as fifth-line of treatment in a patient with metastatic HER-2 positive breast cancer.

The authors present a case of an 80-year-old Caucasian male with multiple gastric and rectal metastases from malignant melanoma presenting with hypochromic anemia as the sole symptom of disease without evidence of cutaneous and ocular tumor localization. The patient had a medical history positive for malignant lentigo melanoma of the occipital region of the scalp and early stage laryngeal squamous cell carcinoma and prostatic carcinoma treated with radiation therapy. The authors make some considerations on intestinal involvement by metastatic melanoma and discuss the choice of not treating with endoscopic procedures the gastric metastatic lesions most likely responsible for the clinical sign present at diagnosis. The patient was referred to clinical oncologists and received immunotherapy with ipilimumab and pembrolizumab.

Introduction: Radium-223 (223Ra) improves symptoms and survival in patients with bone metastatic castration-resistant prostate cancer (mCRPC). Study aim: To evaluate the impact of a previous radical prostatectomy (RP) on the outcome of 223Ra therapy in mCRPC patients. The primary prostate tumor left untreated could progress during 223Ra treatment. Materials and methods: mCRPC symptomatic patients treated with 223Ra were enrolled. Luteinizing Hormone-Releasing Hormone analogue was maintained. No other anticancer therapy was given. 223Ra was administered i.v. at the dose of 55 kBq/kg every 4 weeks for 6 cycles. Patients were stratified according to previous RP or not. Hematological toxicity was monitored. Statistical analysis of 223Ra discontinuations, progressions, and deaths were performed. Results: Forty-four patients were enrolled, 16 (36.4%) previously received RP, 5 (11.3%) prostate radiotherapy and 23 (52.3%) maintained the primary prostate tumor after local treatment. All patients presented only bone metastases, 24 patients (54.5%) had more than 20. Twenty-six (59.1%) patients were treated after first or second line systemic chemotherapy. Treatment interruptions occurred in 14 patients (50%) with prostate and in 4 (25%) without (P = 0.04). After a median follow-up of 18 months (6−30 months), 15 (53.6%), and 7 (43.7%) progressions (P = 0.34) and 13 and 1 (6.2%) deaths (P = 0.04) occurred in patients with and without prostate respectively. Conclusion: The presence of the primary prostate tumor seems to play a detrimental role in mCRPC patients undergoing 223Ra treatment in absence of other concomitant anticancer therapy. On the other hand a previous RP might play a protective role. 2019 Elsevier Inc. All rights reserved.

Background: Different studies suggest that fulvestrant 500 mg every 28 days (HD-FUL) could be an active treatment in HR+ advanced breast cancer (ABC) patients even treated with aromatase inhibitors in the adjuvant setting. The aim of this analysis is to describe the outcome of ABC patients treated with HD-FUL as first-line treatment in terms of median duration of treatment and the overall response rate in a real-world setting. Methods: For the purpose of the present analysis, we considered two data sets of HR+ ABC patients collected in Italy between 2012 and 2015 (EVA and GIM-13 AMBRA studies). Results: Eighty-one and 91 patients have been identified from the two data sets. The median age was 63 years (range 35–82) for the EVA and 57.8 years (range 35.0–82.3) for the AMBRA patients. ORRs were 23.5 and 24.3% in the whole population, 26.9% in the patients with bone only, and 21.8 and 21.4% in those with visceral metastases. The median duration of HD-FUL was 11.6 months (range 1–48) and 12.4 months (range 2.9–70.0) in the two data sets, respectively. Conclusion: These data suggest that HD-FUL should still continue to play a significant role as first-line therapy in HR+ ABC patients.

Background The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial. Methods The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Patients were classified according to the anatomic and the prognostic stage. Distant disease-free survival (DDFS) was calculated from randomization to distant relapse or death. Results A total of 1244 patients were included. Compared to anatomic stage, the prognostic stage downstaged 41.6% (n = 517) of patients to a more favorable stage category. Five-year DDFS based on anatomic stage was as follows: IA 96.6%, IB 94.1%, IIA 92.4%, IIB 87.3%, IIIA 81.3%, IIIC 70.5% (P P P = 0.975). Within anatomic stage I, the outcome was similar for patients treated with 9 weeks or 1 year trastuzumab (5-year DDFS 96.2% and 96.6%, P = 0.856). Within prognostic stage I, the outcome was numerically worse for patients treated with 9 weeks trastuzumab (5-year DDFS 93.7% and 96.3%, P = 0.080). Conclusions The prognostic stage downstaged 41.6% of patients, while maintaining a similar prognostic performance as the anatomic stage. The prognostic stage is valuable in counseling patients and may serve as reference for a clinical trial design. Our data do not support prognostic stage as guidance to de-escalate treatment. Trial registration EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

e19389 Background: Financial toxicity (FT) among cancer patients (CP) is multifactorial, arising from both disease-related and non- disease related factors, including socio-cultural, environmental, and psychological attributes. It derives both from costs related to assistance and borne on the patients and its caregivers, and reduction of income capacity also in this case borne on the patients and on the caregivers. Stress levels may escalate to significant proportions in some patient, to present with symptoms of anxiety especially during therapy administration periods. Methods: In order to highlight financial toxicity related to the diagnosis of metastatic pancreatic and lung cancer and to measure its evolution over time and any correlation with the prognosis, we developed a questionnaire called FT16 and we conducted a validation study on a sample of 31 patients. The design of the study involved the development and the psychometric assessment of a scale to measure the perceived sources of FT among CP. Following extensive literature review, a table of specification with the initial items was created to guide item construction for developing the scale. The items related to these FT were converted into an 16-item, multipoint questionnaire, resulting in the FT16. We also monitored quality of life of the patients, using the QlQ C-30 questionnaire, in the aim to capture correlation between FT onset and quality of life deterioration; clinical characteristics of the patients, response to therapy and outcome parameters also have been recorded in the aim to evaluate eventual correlation with FT. Results: The questionnaire was administered to 31 adult patients with lung and pancreatic metastatic cancer, both men and women, who were newly diagnosed and will undergo cancer treatment. Each of them has been informed about the research and written informed consent has been obtained. The internal consistency reliability (Cronbach’s alpha) was 0.77 for the 16 items of the FT16. Analyses of variance (ANOVAs) indicated that there were no significant differences in the mean FT16 score, between sexes, and age groups in the severity score. Conclusions: FT16 questionnaire seems to be an useful tool to capture FT onset in this poor-prognosis subset of patients; the analysis of the data recorded will continue to assess the capability of the FT16 to capture correlations with clinical characteristics at diagnosis and correlations with the prognosis.

e21580 Background: EGFR tyrosine kinase inhibitors (TKIs) represent the standard first-line therapy for advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, despite initial marked responses, tumors invariably develop acquired resistance to TKIs. Oligoprogression is commonly observed during treatment with oncogene-directed therapies, including EGFR TKIs, and refers to patients who experience disease progression only in limited sites as a result of heterogeneous mechanisms of resistance. The use of local ablative treatments for these resistant lesions may extend the duration of TKI therapy and potentially improve long-term disease control and survival. We e retrospectively analyzed the efficacy of EGFR TKI therapy continuation with high-dose hypofractionated radiation therapy (RT), in EGFR-mutant NSCLC patients with oligoprogressive disease. Methods: Patients with metastatic EGFR mutant NSCLC who developed oligoprogression during first-line treatment with gefitinib were included in this analysis. We evaluated progression-free survival 1 (PFS 1), defined as the time from initiation of TKI therapy until development of oligoprogression or death, and PFS 2, defined as time of focal progression until further progression of disease or death. Overall survival and safety were also assessed. Results: Thirty-six patients were included in the study. The median PFS 1 was 12.5 (4.0-23.2) months. High-dose hypofractionated RT consisted of intensity-modulated RT in 23 patients (64%) and stereotactic radiotherapy in 13 cases (36%). The median PFS 2 was 6.3 (2-12.5) months. Overall survival was 38.7 months (9.0-46.3). The treatment was well-tolerated and no patient had to discontinue TKI therapy because of adverse events during radiotherapy. Conclusions: Our therapeutic strategy, including high-dose hypofractionated RT in addition to TKI therapy, was feasible in the clinical setting and was associated with significant prolongation of disease control and improvement of survival outcomes, while being associated with manageable side effects. Our study further support the use of definitive therapeutic approaches in oligoprogressive disease, especially in oncogene-driven tumors. Molecular profiling of metastatic sites remains crucial to identify novel biomarkers, involved in the development of acquired resistance and oligoprogression, that may be useful to select patients for local treatments.

Background In Italy, previously untreated patients with RAS wild-type metastatic colorectal cancer (mCRC) may receive an epidermal growth factor receptor (EGFR) inhibitor with a chemotherapy regimen (CT). The choice of anti-EGFR, either cetuximab (cet+CT) or panitumumab (pan+CT), depends on various factors, including adverse event (AE) profiles. Although AE profiles will evolve with increasing use and familiarity, the differences in AE profiles can be explored using literature and safety data from the summary of product characteristics (SmPC). The financial impact of these differences on the Italian National Health Service has yet to be estimated. Methods We developed a model to estimate costs of AE management. Frequencies of common and very common AEs associated with cet+CT or pan+CT were sourced from the respective SmPC.1,2 Applicable resource use costs were obtained from hospital services price lists from the Ministry of Health using the DRG outpatient tariff.3 The national-level financial impact was calculated from the number of cet+CT–eligible patients with mCRC treated in the first line based on published literature, national guidelines, and pan+CT market share. Inputs were validated by practicing Italian oncologists. Results All-grade AEs were estimated to be 58.1% lower and grade 3/4 AEs were estimated to be 70.2% lower in patients receiving cet+CT than in those receiving pan+CT. Mean costs of AE management per patient treated with cet+CT and pan+CT were estimated at €1,194 and €2,951, respectively, resulting in average savings of €1,758 (59.6%) per patient. Differences are mainly driven by a lower frequency of AEs that are costly to manage, such as GI disorders. Annual savings could reach €2,191,839 for a population of 1,247 cet+CT–eligible patients with mCRC. Conclusions Fewer AEs for cet+CT may result in markedly lower AE management costs vs pan+CT. Although results should be considered together with overall costs and clinical outcomes, cet+CT could decrease cost burden on the Italian National Health Service and AE burden for patients with mCRC. Editorial acknowledgement ClinicalThinking, Inc, Hamilton, NJ, USA (funded by Merck Healthcare KGaA, Darmstadt, Germany). Legal entity responsible for the study Merck Healthcare KGaA. Funding Merck Healthcare KGaA. Disclosure N. Personeni: Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono. V. Gebbia: Honoraria (self): Merck; Honoraria (self): Amgen; Honoraria (self): Roche. P. Novelli: Full / Part-time employment: Merck Serono S.p.A. S. Di Matteo: Research grant / Funding (institution): Merck. G. Colombo: Research grant / Funding (institution): Merck. C. Pescott: Full / Part-time employment: Merck Healthcare KGaA. All other authors have declared no conflicts of interest.

Purpose To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non–small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC.

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency.

Introduction Cisplatin with pemetrexed (CP) and carboplatin with paclitaxel and bevacizumab (CbTB) are standard first-line treatments for patients with advanced nonsquamous (NS) non–small-cell lung cancer (NSCLC). Quality of life (QoL) is a key objective in the management of advanced NSCLC. Thus, effect on QoL could be an additional factor in the choice of treatment. Patients and Methods Patients with untreated stage IIIB/IV NS-NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomized to receive first-line chemotherapy with cisplatin 75 mg/m 2 and pemetrexed 500 mg/m 2 , every 3 weeks, for 6 cycles followed by maintenance pemetrexed; or carboplatin area under the curve 6, paclitaxel 200 mg/m 2 , and bevacizumab 15 mg/kg, every 3 weeks, for 6 cycles followed by maintenance bevacizumab. The primary end point was the difference in QoL between the 2 treatment arms after 12 weeks of maintenance, measured using the EuroQoL 5 Dimensions-Index (EQ5D-I) and EQ5D-visual analogue scale (EQ5D-VAS). Results One hundred eighteen patients were randomized to CP (n = 60) or CbTB (n = 58). Baseline characteristics were well balanced. The proportion of patients evaluable for the primary end point was lower than planned. After 12 weeks of maintenance, the difference between mean changes in EQ5D-I was 0.137, favoring CP (95% confidence interval [CI], −0.02 to 0.29, Wilcoxon P = .078), although not statistically significant; and the difference between mean changes in EQ5D-VAS was 0.97 (95% CI, −9.37 to 11.31, Wilcoxon P = .41). Conclusion Although the study was underpowered because of a small number of patients evaluable for the primary end point, QoL did not differ between treatment arms. Other factors such as comorbidities and schedule should be used when deciding on first-line treatment.

e12552 Background: mCHT is the minimum biologically effective dose of a chemotherapeutic agent, given at regular dosing regimen with no prolonged drug free interval, that leads to anti-tumor activity. Old regimens included Cyclophosphamide-Methotrexate (CM), whereas in the last years new regimens, such as Vinorelbine (VRL) and Capecitabine (CAPE)-based have been developed. Aim of this observational retrospective ongoing study is to describe the use of mCHT in ABC pts across 5 years and the clinical characteristics of the pts together with efficacy of old (CM-like) vs new (VRL/CAPE-based) metronomic regimens in terms of response and disease control. Methods: We retrospectively identified from clinical records those HER2-ve ABC pts who have received any kind of mCHT in the years 2011-2015, alone, or in combination with a non-metronomic drug. Standard statistical approaches were used for describing the sample characteristics. Logistic and non proportional hazard analysis were used to identify factors associated with response, and time to treatment failure and survival, respectively. This preliminary analysis focuses on Response Rate (RR) and Disease Control Rate (DCR). Results: From June 2011 to December 2015, 267 pts have been identified till now and 233 are fully evaluable. Median age at mCHT start was 67 years. 81% was HR+ and 33% had non-visceral metastatic disease. 22% of the pts received CM, 55% VRL-based and 23% mCAPE-based regimens. mCHT use increased over the time from 15.0% (2011) to 30% (2015). As 1st-line treatment, CM was administered in 27% of compared with more than 48% of patients receiving CAPE/VRL-based regimens. Overall Response Rate (ORR) was 28% and Disease Control Rate (DCR) was 79%. Median duration of mCHT was 6.2 months. New generation metronomic regimens produced higher ORR in comparison to old ones (32% vs 13.5%), with similar duration of treatment (6.4 vs 5.4 months, respectively). Conclusions: The use of mCHT in the treatment of HER2-ve ABC pts has deeply changed across the last 5 years, being new generation regimens used in earlier lines of treatment, producing interesting results in terms of objective response and disease control.

Background: In vitro data suggest that panobinostat (LBH589), a pan-deacetylase inhibitor, may add therapeutic benefit in the treatment of small-cell lung cancer (SCLC) with regression of tumors. Methods: This multicenter, nonrandomized phase 2 trial was designed to evaluate antitumor activity of LBH589 in patients with previously treated SCLC. Patients received LBH589 administered intravenously at a dose of 20 mg/mq (days 1–8) every 21 days. Results: A total of 21 patients with extensive- or limited-stage SCLC were enrolled. Patients received a median of two cycles (range, 1–6). LBH589 was well tolerated, and the most common toxicities were grade 1 to 2 gastrointestinal disorders (nausea 38%, diarrhea 24%, vomiting 19%), grade 1 to 2 thrombocytopenia (14.3%). Of 19 patients evaluable for efficacy, two cases showed shrinkages more than 30% at first assessment, with time to progression of 14 and 21 weeks, respectively, and there were three long disease stabilizations of 12, 10, and 13 weeks. The study was prematurely closed because of a lack of activity. Conclusion: This is the first report of a pan-deacetylase inhibitor inducing tumor shrinkage and sustained stable disease in SCLC. We believe that although the trial was prematurely discontinued, modest clinical activity of LBH589 combined with a favorable safety profile in pretreated SCLC patients was observed, which warrants further exploration of the potential contribution of LBH589 in other trials.

BackgroundSeveral studies have emphasized the importance of the maintenance of bone health in a comprehensive cancer care. However, no survey about approach to bone metastasis care is currently available. The ZeTa study provides a picture of the Italian oncologists' therapeutics habits in this area, in a real clinical-practice scenario.DesignThis study was based on online questionnaire-based interviews to Italian oncologists that included 145 questions. The aim was to collect information on the treatment of bone metastasis, the current use of bisphosphonates, the awareness of guidelines and the concerns about ONJ, the use of vitamin D supplementation.Results445 oncologists were contacted, 283 agreed to participate. The results show that the current management of bone metastasis is still sub-optimal, as the recommendations from current clinical guidelines are not completely followed by all specialists.ConclusionsThis survey highlights the urgent need to improve management of bone metastasis in cancer patients.

In the nineties, spinal analgesia has been described as an useful means to control pain in advanced cancer patients. The aim of this review was to update this information with a systematic analysis of studies performed in the last 10 years. 27 papers pertinent with the topic selected for review were collected according to selection criteria. Few studies added further information on spinal analgesia in last decade. Despite a lack of a clinical evidence, spinal analgesia with a combination of opioids, principally morphine, and local anesthetics may allow to achieve analgesia in patients who had been intensively treated unsuccessfully with different trials of opioids. Some adjuvant drugs such as clonidine, ketamine, betamethasone, meperidine, and ziconotide may be promising agents, but several problems have to be solved before they can be used in the daily practice. In complex pain situations, spinal analgesia should not be negated to cancer patients, and oncologists should address this group of patients to other specialists.

Introduction: To date, orally administered chemotherapy and biologic agents represent a significant percentage of all antineoplastic treatments in several types of cancer, which are most likely to increase in the near future. In this scenario, the issue of adherence and persistence to oral therapy is a key issue since poor compliance to oral antineoplastic treatments may negatively influence patients' clinical outcomes and, in turn, cause an increase in costs, number of hospitalizations and time spent in the hospital. Areas covered: The issue of adherence to new oral chemotherapeutic and/or biologic agents has not been deeply evaluated and data published in medical literature are quite scarce. Adherence is a multidimensional phenomenon, which may be influenced by patient-and health-care provider-related factors, anticancer therapy itself, education and socioeconomic aspects. Patients' selection plays, therefore, a key role in maximizing adherence and persistence to oral therapies. Treating health-care practitioners should first evaluate patient reliability to avoid prescribing oral treatments to patients with socioeconomic and medical conditions, which may predict poor adherence. Expert opinion: Adherence and persistence to new oral biologic agents, which are linked to several side effects and whose use is constantly widening, should represent a main endpoint of clinical research in the nearest future. © 2012 Informa UK, Ltd.

Lung cancer is the most common cancer in the world today, in terms of both incidence and mortality. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers, and the majority of people diagnosed with NSCLC have locally advanced or metastatic disease. Treatment algorithms have rapidly changed in the last 10 years because of the introduction of new chemotherapeutic and targeted agents in clinical practice. SUN is a 1-year longitudinal observational multicenter study that has consecutively enrolled patients affected by stage IIIB or IV NSCLC with the aim to describe the pattern of care and evolving approaches in the treatment of advanced NSCLC. 987 consecutive NSCLC patients were enrolled between January 2007 and March 2008 at the 74 participating centers throughout Italy and a 12-month follow-up was performed. Cyto-histological diagnosis was performed mainly by broncoscopy with only 24% by CT-scan guided fine-needle aspiration biopsy. 91.4% of the patients received a first-line medical treatment and 8.6% supportive care only. Median age of patients receiving first-line treatment was 66 years. First-line chemotherapy consisted of a single agent in 20% of patients and combination chemotherapy in 80%. The most frequently used chemotherapy regimens were cisplatin plus gemcitabine and carboplatin plus gemcitabine. Median survival of patients receiving first-line chemotherapy was 9.1 months. 32% percent of patients received a second-line treatment that consisted of chemotherapy in 71% of cases and erlotinib in 29%. Overall third-line treatment was given to 7.3% of patients. These results showed a pattern of care for advanced NSCLC that reflects the current clinical practice in Italy at the study time with a high adherence to the International guidelines by the Italian Oncologists. Keywords Advanced NSCLC; Observational study; Chemotherapy; Platin-based chemotherapy; Pemetrexed; Docetaxel; Targeted therapy; Erlotinib

The aim of this study was to determine the activity and toxicity of two sequential chemotherapy regimens in the first-line treatment of advanced non-small-cell lung cancer (NSCLC).Eighty-eight chemonaive patients with stage IIIB/IV NSCLC were randomised to receive either three cycles of 75 mg/m(2) cisplatin plus 75 mg/m(2) docetaxel, both administered on day 1 every 21 days, followed by three cycles of 1,200 mg/m(2) gemcitabine on days 1 and 8 every 3 weeks (arm A), or three cycles of 25 mg/m(2) cisplatin plus 25 mg/m(2) docetaxel on days 1, 8 and 15 every 28 days, followed by three cycles of 1,200 mg/m(2) gemcitabine on days 1 and 8 every 3 weeks (arm B).Of the evaluable patients, 61% in arm A (n = 41) and 36% (n = 44) in arm B completed treatment as per the protocol. The best tumour response rates were as follows (arm A and arm B): complete response: 2.4 and 2.3%; partial response: 39 and 20.4%; stable disease: 26.8 and 13.6%; and progressive disease: 31.8 and 45.4%. The median progression-free and overall survival were 3.9 and 12.3 months in arm A, respectively, 3.1 and 7.7 months in arm B. Grade 3-4 adverse events were more common in arm A. Grade 3-4 neutropenia was the main toxicity observed (56.1% in arm A and 11.4% in arm B).Our data demonstrate the feasibility of a sequential approach of cisplatin plus docetaxel followed by single-agent gemcitabine. Weekly administration of platinum-docetaxel is associated with an improved safety profile but lower efficacy than the conventional three-weekly schedule (registration ID 2004-001044-72).

Background More than 50% of brain metastases (BMs) occur in advanced non-small cell lung cancer (NSCLC) patients. Untreated patients with BMs have a poor prognosis with a median survival of 2 months. In most cases BMs are multiple and their optimal therapy is whole-brain radiation therapy (WBRT). The role of systemic therapies for these patients is still a matter for investigation due to concerns about the ability of these drugs to cross the blood–brain barrier (BBB). Cisplatin (CDDP) remains the backbone for medical treatment of NSCLC and fotemustine (FTM) is a nitrosurea able to cross the BBB. Methods Patients with advanced NSCLC, ECOG performance status (PS) 0–1 and multiple BMs not amenable to surgery or stereotactic radiotherapy were treated with 2 cycles of FTM 80 mg/m2 days 1, 8 and CDDP 80 mg/m2 day 1, every 3 weeks followed by WBRT 30 Gy (3 Gy daily in 10 fractions). Radiological restaging was performed before WBRT to assess the role of chemotherapy both for cranial and extracranial disease. Patients with disease control (DC: complete response plus partial response) received 4 more cycles. To assess the basic activities of daily living (ADL), the Barthel ADL Index was used to score patients’ performance every 2 cycles. The trial design provides a two-step evaluation according to the optimal two-stage design of Simon. In the first phase 29 patients were enrolled in order to verify if this schedule showed more than 25% response rate both for cranial and extracranial disease. If so, enrolment added up to a total of 81 patients. Results After the first evaluation 4 out of 29 patients were excluded from the study (3 untreated/1 not included for administrative reasons). At the time of the planned interim analysis patient's characteristics were the following: median age 61 years (range 44–70), M/F = 16/9, adenocarcinoma 11, squamous 5, large cell 2, undefined NSCLC 7; PS 0/1 in 11/14 cases, median Barthel Index score was 20 [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] . Three (12%) partial responses were observed, 9 subjects (36%) with stable disease and 13 (52%) showing disease progression. These data did not satisfy the pre-planned hypothesis and the study was stopped. At the time of the first evaluation before WBRT 12/25 (48%) patients had a systemic DC in contrast with 15/25 (60%) patients with BMs DC. Chemotherapy was relatively well tolerated with a prevalence of asthenia as the most relevant specific toxicity while the haematological toxicity was mild. Conclusion CDDP and FTM combined with WBRT do not represent a therapeutic option for patients with NSCLC. Therefore further studies to evaluate the combination of systemic treatments with WBRT are warranted.

at present, there is very little data available about the impact of anemia on elderly cancer patient's quality of life (QoL). Most of the acquired knowledge has been derived from small studies selected for primary site cancer. This observational study investigates the association between hemoglobin (Hb) level and comprehensive geriatric assessment variables: Cancer Linear Analog Scale (CLAS), Activities of Daily Living (ADL), Mini-Mental State Examination (MMSE) in elderly cancer patients undergoing chemotherapy (CT).we enrolled 586 elderly cancer patients undergoing CT who were evaluated at baseline and every 3-4 weeks for at least 12 weeks. The correlation between Hb level changes and the examined index changes were performed using Pearson correlation analysis and a multivariate analysis was performed using a logistic regression model.both univariate and multivariate analyses at baseline showed that Hb values are related to ECOG performance status (PS), stage of disease and self-reported QoL. Hb level variation significantly correlated with CLAS and ADL changes measured at baseline and after 12 weeks. This correlation is highly significant in patients with Hb11g/dl. Multivariate analysis showed that Hb change of at least 1g/dl was the only independent predictor of a better quality of life, when assessed by using the CLAS and ADL questionnaire (p0.05). Moreover the median time of hospitalisation was found to be significantly lower in patients showing higher Hb level (Hb ≥ 11g/dl) (p=0.037).the findings of this study seem to provide adequate support for the correlation between anemia and elderly cancer patient's QoL. Interestingly, we reported an association between anemia and the length of hospitalisation in this setting of patients. However, the above results do need to be confirmed by further prospective trials.

Introduction: Several large randomized trials have shown the superiority of combining trastuzumab with chemotherapy versus chemotherapy alone as adjuvant treatment for HER2+ breast cancer patients. We are running a large phase III trial comparing two different trastuzumab durations (Short-HER study). We are reporting the preliminary cardiac safety data. Methods: The Short-HER study is a phase III, multicentric, Italian trial where 2500 HER2+ breast cancer patients will be randomized to: Arm A (Long) 4 courses of anthracycline based chemotherapy (AC or EC) followed by 4 courses of docetaxel in combination with trastuzumab, followed by 14 additional courses of 3-weekly trastuzumab; or Arm B (Short) 3 courses of 3-weekly docetaxel in combination with weekly trastuzumab followed by FEC x3. this is a non-inferiority trial with DFS and OS as primary end points, and 2-yr failure rate and incidence of cardiac events as secondary end points. Left ventricular ejection fraction (LVEF) is measured at baseline, at the end of each sequence of chemotherapy in both arms, and after 9 and 12 months since randomization thereafter. A cardiac event (CE) was defined as the occurrence of any of the followings: 1) LVEF decrease of more than 15 percentage points from baseline ; 2) LVEF decrease of more than 10 percentage points with absolute value below 50%; 3) symptomatic cardiac failure; 4) other cardiac side effects of grade 2 or more. Results: 510 patients from 69 Italian centers have been randomized so far, 251 in arm A (long) and 259 in Arm B (Short). 146 patients enrolled in arm A and 150 patients enrolled in arm B have received at least 3 months of therapy, and are eligible for the present analysis. In arm A (long), 20 patients (13.7%) experienced a CE: 12 patients experienced a LVEF decline of > 15 percentage points (5 patients with LVEF below 50%, one patient with concomitant atrial fibrillation); 3 patients had a LVEF decline of >10 percentage points with an absolute value below 50%. One patient had symptomatic cardiac failure. Two patients developed Grade 2 hypertension. Two patients developed Grade 2 arrhythmia. In arm B (short), 11 patients (7.3%) experienced a CE: 7 patients had a LVEF decline of > 15 percentage points; one patient had a LVEF decline of > 10 percentage points with an absolute value below 50%. Three patients developed Grade 2 arrhythmia Conclusions: This is a non-inferiority study designed on the assumption that a shorter treatment duration is associated with a significantly lower incidence of cardiac events. With 9 clinically relevant CEs (symptomatic cardiac failure or LVEF below 50%) in arm A (Long) and 1 in arm B (Short), these preliminary data support the assumption, and recruitment is ongoing. Supported by Agenzia Italiana del FArmaco (AIFA). Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-12-05.

Patients with advanced pancreatic cancer failing gemcitabine-based first-line chemotherapy are still in relatively good clinical conditions and may still require second-line chemotherapy, which is frequently administered in daily clinical practice given to without solid scientific support.A retrospective survey was carried out including 40 patients with stage III or IV gemcitabine-refractory pancreatic carcinoma. Patients received standard FOLFIRI regimen biweekly until progression or unacceptable toxicity. Response evaluation criteria in solid tumors and National Cancer Institute common toxicity criteria were employed respectively for response and toxicity assessment.Six partial responses (15%) and 14 stabilizations of disease (35%) were recorded for a tumor growth control rate of 50%. The median time to progression was 3.7 (range, 1-6.5 months), and median overall survival was 6 months (range, 2-8.2 months). A stabilization of performance status and a subjective improvement of cancer-related symptoms were recorded in 21 patients (52.5%). No correlation has been found between length of time to progression during first-line chemotherapy and length of that reported in the second-line setting or objective response. Grade 3-4 diarrhea and mucositis was observed in 15% and 10% of cases, respectively.Data presented in this article demonstrate that the second-line FOLFIRI regimen are able to induce an objective response in a relatively small fraction of patients with gemcitabine-refractory adenocarcinoma of the pancreas. The use of second-line chemotherapy should be carefully proposed to patients with good performance status or those who had a good response to first-line therapy.

Background Quality of life (QoL) has gained greater importance in the management of metastatic non-small-cell lung cancer due to the palliative nature of treatment. Docetaxel (DCT) and cisplatin (CDDP) doublet has been reported to be associated to a better QoL than the weekly vinorelbine (VNR) and CDDP regimen. Recently a newer more tolerated schedule of the VNR/CDDP regimen has been published and is widely employed in medical practice. The impact of these regimens on patients' QoL as well as symptoms control and type and grading chemo-related side-effects has been compared prospectically. Methods Patients received CDDP 75mg/m 2 plus DCT 75mg/m 2 on day 1 every weeks (arm A) or CDDP 80mg/m 2 on day 1 plus VNR 30mg/m 2 day 1 and 8 every 3 weeks (arm B). G-CSF and/or EPO were employed as needed. Health-related QoL was assessed at entry and after every cycle by the EORTC-QLQ-C30 and LC13 questionnaires, toxicity by the NCI-NCCN CTC vs 2, and intent-to-treat objective response by the Recist criteria. Results The QoL questionnaires were completed by 37 pts (88%) in the DCT/CDDP arm and 39 pts (87%) in the VNR/CDDP one. Baseline mean scores and rates at which pts failed to complete QoL assessment were similar in the two arms. Global health status of the EORTC QLQ-C30 scale and specific symptoms control (LC13 module) improved during treatment without any statistically significant difference between the two arms. Emotional functioning remained stable in both groups during treatment, whereas physical and role improved slightly. In the DCT/CDDP arm 14 pts (33%; 95%CL 24–40%) had PR, and 10 (24%) SD for a 57% TGCR. In the VNR/CDDP arm 12 pts (27%) achieved PR, 18 (41%) SD a 68% TGCR. Differences were not statistically significant. Median time-to-progression was 4.2 months in the DCT/CDDP arm and 4.5 months in the VNR/CDDP one, and median overall survival was 12.1 (range 1–26+ months) and 12.5 months (range 1–28+ months) for DCT/CDDP and VNR/CDDP arms, respectively. Febrile neutropenia rate was higher in the VNR/CDDP arm ( p =0.02) as well as G3-4 anemia ( p =0.005) and G-CSF/EPO use ( p =0.019). Conclusions Global and specific health-related QoL data similar in both treatment groups with no statistically significant difference. Efficacy measures, overall response rate, time-to-progression and overall survival were equivalent in both arms. However, severe anemia and febrile neutropenia are statistically more frequent in the VNR/CDDP arm than in the DCT/CDDP one. These data should be considered in treatment decision-making for pts with advanced non-small-cell lung cancer and for the design of future trials with chemotherapy plus biologics.

Purpose: Knowledge of prognostic factors for advanced non-small-cell lung cancer (NSCLC) patients eligible for second-line treatment is scarce. The aim of this study was to assess the prognostic role of a number of routinely collected clinical variables and to provide a summary index to discriminate patients according to probability of survival.Methods: individual data from nine randomised trials of second-line treatment in advanced NSCLC were analysed. Primary end-point was overall survival (OS). Cox model, stratified by trial, was used for multivariate analyses, and a prognostic index was provided and validated according to an internal/external procedure.Results: Out of 1239 patients, 1197 patients (97%) had complete information. Median OS was 7.4 months. At multivariate analysis, prognosis was significantly influenced by gender (worse in males), performance status (PS), tumour histology (worse in squamous and other histology versus adenocarcinoma), stage (worse in IV versus IIIB), type of previous treatment (worse for patients pretreated with platinum) and response to first-line (worse for patients not obtaining objective response). Prognostic score values ranges from 0 to 14. When three categories were derived, median overall survival values were equal to 11.6, 7.5 and 3.0 months for best (9) category, respectively.Conclusion: Prognosis of patients eligible for second-line treatment of advanced NSCLC is significantly conditioned by gender, PS, histology, stage, previous use of platinum and response to first-line. A prognostic score was derived that discriminates well subjects with a relatively more favourable prognosis and those with very short life expectancy. (C) 2009 Elsevier Ltd. All rights reserved.

Capecitabine is an oral chemotherapeutic agent, already used in breast and colon cancer. Previous data showed encouraging results in the treatment of recurrent ovarian cancer. The aim of this study was to describe activity and toxicity of capecitabine in patients with platinum resistant or refractory ovarian cancer. Patients were eligible if they had cytologically or histologically proven epithelial ovarian cancer, refractory or resistant to prior platinum-containing chemotherapy. Capecitabine was administered at the dose of 1,250 mg/m2 twice daily on days 1–14 of a 21-day cycle for a maximum of six cycles. The primary end point of the study was activity in terms of objective response rate in according to RECIST criteria. A two-stage minimax design for phase II studies was used: at least four objective responses had to be reached among 32 evaluable patients to define the treatment active. Between March 2006 and October 2007, 36 patients were enrolled. All patients had ovarian cancer and 83.3% had previously received two or three lines of chemotherapy. Thirty-two patients were evaluable for response and included in the activity analysis. The objective response rate was 3.1% [95% exact confidence interval (CI): 0.08–16.22%], lower than the threshold required to define the treatment as active. The median progression free survival was 68 days (95% CI: 65–120). Haematological toxicity was not frequent. Nausea and fatigue were common, but never severe, and they were observed in 13 (37.1%) and 12 (34.2%) patients, respectively. Diarrhoea occurred in 11 patients (31.5%) and it was of grade 3 in 8.6% of cases. Grade 1–2 stomatitis was observed in seven patients (20%). Cardiovascular toxicity was reported in two cases, including a death for pulmonary embolism. Capecitabine is not active in platinum resistant non mucinous ovarian cancer, producing a response rate lower than that required by study design. Further trials are not warranted in these patients.

Background Doublet chemotherapy is more effective than single-agent as first line treatment of advanced non-small-cell lung cancer (NSCLC). No reliable information instead is available on the effect of doublets in second line treatment. The aim of DISTAL-2 study was to compare two doublets containing docetaxel with single agent docetaxel as second line treatment of patients with NSCLC (ClinicalTrials.gov id.:. NCT00345059 ). Methods NSCLC patients, aged 2 on days 1, 8, 15 q 4 weeks); arm B, weekly docetaxel (30 mg/m 2 on days 1, 8, 15) plus gemcitabine (800 mg/m 2 on days 1, 8 q 4 weeks) or plus vinorelbine (20 mg/m 2 on days 1, 8 q 4 weeks) depending on which of the two had been used in first line; arm C, weekly docetaxel (as in arm B) plus capecitabine (625 mg/m 2 twice daily on days 5–18 q 4 weeks). Primary end-point was overall survival (OS). Two comparisons were planned: arm B vs. A and arm C vs. A. Overall, 375 patients had to be randomized. Response was assessed by RECIST, quality of life (QoL) by EORTC questionnaires. Results 84 patients were randomized from May 2005 to December 2006, when the trial was prematurely stopped due to the slow accrual. After 62 deaths, median OS was 40.0 weeks in arm A, 32.6 weeks in arm B ( p = 0.18 vs. A) and 39.7 weeks in arm C ( p = 0.90 vs. A). Response rate was 6.4, 16.7 and 5.3%, and median progression-free survival was 12.4, 13.1 and 11.9 weeks, for arms A, B and C, respectively. Patients in arm B had significantly more grade 3–4 haematological and non-haematological toxicity compared to arm A, and patients in arm C had significantly more grade 3–4 non-haematological toxicity compared to arm A. No relevant differences were found in QoL analysis, with the exception of significant worsening in appetite, vomiting and hemoptysis for patients in arm B. Conclusion Due to early termination, the trial does not have the planned statistical power. However, available data do not support the role of docetaxel-based combination chemotherapy as second line in advanced NSCLC.

This paper is an updated review of the pre-clinical rationale and clinical results of new EGFR-targeted agents – cetuximab and panitumumab – employed in the management of advanced/ metastatic colorectal cancer. The addition of either biologic agent or last generation standard chemotherapy regimens – FOLFIRI and FOLFOX – has yielded better results as compared to those reported for chemotherapy alone. These results have been obtained without a significant increase in severe toxicity with the exception of skin side-effects.

BackgroundThis study was carried out to evaluate total basal bilirubin levels as a predictive factor for survival and toxicity in patients with advanced colorectal carcinoma treated with CTP-11-based regimens.Patients and methodsThe analysis was carried out on a data base including 287 patients affected by advanced colorectal carcinoma all treated with CPT-11 plus bolus and continuous venous infusion intravenous folinic acid and 5-fluorouracil on a biweekly schedule (FOLFIRI regimen). Patients were divided into four groups according to basal bilirubin levels as follows: 0.50 and 1.00 and 1.50mg/dl. Analysis of overall median survival and time-to-progression were correlated to performance status at entry, volume of liver metastases, and carcinoembrionary antigen.ResultsGlobal statistical analysis showed that bilirubin levels were strongly correlated with time-to-progression and overall survival in a statistically significant fashion (p

A growing percentage of patients affected by advanced non-small cell lung cancer who progressed after first-line chemotherapy still have a good performance status and require second-line treatment.An overview of the state of the art of second-line therapeutic options is presented.The scope of the review is to give an update on the therapeutic options currently available for the second-line treatment of patients with advanced non-small cell lung cancer.Among chemotherapeutic drugs docetaxel and pemetrexed have been approved for second-line treatment of advanced non-small cell lung cancer. Although the drugs are equiactive in terms of response rate and survival parameters the latter has a clear-cut advantage in terms of tolerability and quality of life. Therefore, pemetrexed is considered the best second-line therapeutic option in order to avoid severe side effects. Among biologic agents the tyrosine kinase inhibitors gefinitib and erlotinib have been largely tested, but only the latter has been approved for second- and third-line treatment. Erlotinib has been reported to be particularly active in patients with adenocarcinoma, in females, in patients of Asian ethnicity and in epidermal growth factor receptor mutations and it is also active in the third-line setting. At present, no direct head to head comparison of erlotinib with any chemotherapeutic agent has been performed. A rational decision tree may therefore include pemetrexed or docetaxel (the former preferred for tolerability) or erlotinib as standard second-line therapy. Erlotinib has been also shown to be active as third-line treatment: however, in cases of patients with clinical characteristics suggesting a good response to tyrosine kinase inhibitors, erlotinib may be employed in an earlier phase.

Summary Background The addition of cyclo-oxygenase-2 (COX-2) inhibitors and prolonged constant infusion (PCI) of gemcitabine to treatment for advanced non-small-cell lung cancer (NSCLC) might improve treatment efficacy. We aimed to assess whether the addition of rofecoxib or PCI gemcitabine could improve overall survival compared with first-line treatment with cisplatin plus gemcitabine given by standard infusion. Methods Patients with stage IV or IIIb (with supraclavicular nodes or pleural effusion) NSCLC who were under 70 years of age and who had performance status 0 or 1 were eligible for this multicentre, prospective, open-label, randomised phase III trial with 2×2 factorial design. Patients were randomly assigned to one of four treatment groups: group A, gemcitabine 1200 mg/m 2 in a 30-min intravenous infusion on days 1 and 8 and intravenous cisplatin 80 mg/m 2 on day 1, every 21 days for six cycles; group B, the same treatments as group A plus oral rofecoxib 50 mg/day until disease progression; group C, intravenous PCI gemcitabine 1200 mg/m 2 in a 120-min infusion on days 1 and 8 and intravenous cisplatin 80 mg/m 2 on day 1, every 21 days for six cycles; group D, the same drugs as group C plus oral rofecoxib 50 mg/day until disease progression. The primary endpoint was overall survival; secondary endpoints were progression-free survival, response rate, quality of life, and toxicity. Analyses were intention-to-treat. This trial is registered on the clinical trials site of the US National Institutes of Health website http://clinicaltrials.gov/ct/show/NCT00385606. Findings Between Jan 30, 2003, and May 3, 2005, 400 patients were enrolled. Median age was 60 years (range 29–71). PCI gemcitabine did not improve overall survival (median 47 weeks [95% CI 40–55] vs 44 [36–52], with standard gemcitabine infusion, hazard ratio (HR) of death 0·93 [0·74–1·17], p=0·41), progression-free survival, nor any other secondary endpoint. Vomiting and fatigue were significantly worse with PCI gemcitabine. The two rofecoxib groups were closed early (on Oct 1, 2004) due to withdrawal of the drug because of safety issues. With intention-to-treat statistical analyses limited to 240 patients (ie, those randomised before July 1, 2004) who had at least 3 months of treatment, rofecoxib did not prolong overall survival (median 44 weeks [CI 36–55] vs 44 [40–54] without rofecoxib, and HR of death 1·00 [0·75–1·34], p=0·85), or progression-free survival, but did improve response rate (41% vs 26%, p=0·02), global quality of life, physical, emotional and role functioning, fatigue, and sleeping. Rofecoxib significantly increased the incidence of diarrhoea and decreased constipation, fatigue, fever, weight loss, and pain, and analgesic consumption. Severe cardiac ischaemia was more frequent with rofecoxib than without; however, the difference was not statistically significant in the primary analysis (p=0·06) and became significant when patients who were randomised between July 1, 2004, and Sept 30, 2004, were included in the analysis (p=0·03). Interpretation Neither PCI gemcitabine nor rofecoxib prolonged survival in the patients in this study. Rofecoxib improved response rate and several quality-of-life items, including pain-related items and global quality of life. Further studies with less cardiotoxic COX-2 inhibitors are needed in NSCLC.