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Background: Studies from several countries have documented gender disparities in the management of coronary artery disease. Whether such gender disparities are seen in Italy and, if so, whether they can be explained by factors such as age and severity of illness were investigated. Methods: 77 974 Piedmontese patients, admitted between 1999 and 2002, with a primary diagnosis of myocardial infarction (ICD 410), angina (ICD 413), chronic ischaemia (ICD 414) and chest pain (ICD 786.5) were studied. The number of men and women undergoing surgical treatment was extracted and the male-female odds ratios calculated. Several risk factors and a risk adjustment technique (APR-DRG) were used to control for possible confounders. Backward stepwise multiple logistic regression was used to adjust for significant covariates. Results: Crude analysis demonstrated that gender is a discriminating factor in the probability of surgery (OR 2.11, 95% CI 2.04 to 2.19), with similar findings among those with each main diagnosis. The odds ratios decreased after adjustment for age, co-morbidity and disease severity but remained significant. Conclusions: Men and women admitted to hospitals in a region of northern Italy with a diagnosis of cardiovascular disease are treated differently and this cannot be explained by age or severity of disease. [ABSTRACT FROM AUTHOR]

Purpose: In the absence of clear evidence from randomized trials, the intensity of follow-up regimens after surgical treatment of endometrial cancer is highly variable in clinical practice. To reduce this uncertainty, we conducted a randomized trial to test whether an intensive (INT) versus a minimalist (MIN) follow-up regimen improves overall survival (OS) in patients undergoing operation for endometrial cancer., Methods: The TOTEM study was a large, pragmatic randomized trial, conducted in 42 hospitals (in Italy and France) including patients surgically treated for endometrial cancer, in complete clinical remission, International Federation of Gynecology and Obstetrics stage I-IV. After stratification by center and risk of relapse (low or high), patients were randomly assigned (1:1) to INT or MIN hospital-based follow-up regimens. The study was powered to demonstrate an absolute improvement of 5% of the 5-year OS with the INT regimen., Results: In total, 1,871 patients were randomly assigned between November 2008 and July 2018, and 1,847 patients (98.7%) were available for the final analysis (60% low risk). After a median follow-up of 69 months, the 5-year OS was 90.6% in the INT and 91.9% in the MIN arms (hazard ratio, 1.13, 95% CI, 0.86 to 1.50, P = .380). No differences in OS were found in subgroup analyses considering age, cancer treatment, risk of relapse, and degree of adherence of the center to the scheduled follow-up. The probability of detecting a relapse was slightly higher in the INT arm (hazard ratio, 1.17; 95% CI, 0.92 to 1.48; P = .194)., Conclusion: An INT follow-up in endometrial cancer-treated patients does not improve OS, even in high-risk patients. According to available evidence, there is no need to routinely add vaginal cytology, laboratory, or imaging investigations to the MIN regimens used in this trial.

Introduction: The ERAS protocol (Enhanced Recovery After Surgery) is a multimodal pathway aimed to reduce surgical stress and to allow a rapid postoperative recovery. Application of the ERAS protocol to colorectal cancer surgery has been limited to a minority of hospitals in Italy. To promote the systematic adoption of ERAS in the entire regional hospital network in Piemonte an Audit and Feedback approach (A&F) has been adopted together with a cluster randomised trial to estimate the true impact of the protocol on a large, unselected population., Methods: A multicentre stepped wedge cluster randomised trial is designed for comparison between standard perioperative management and the management according to the ERAS protocol. The primary outcome is the length of hospital stay (LOS). Secondary outcomes are: incidence of postoperative complications, time to patients' recovery, control of pain and patients' satisfaction. With an A&F approach the adherence to the ERAS items is monitored through a dedicated area in the study web site. The study includes 28 surgical centres, stratified by activity volume and randomly divided into four groups. Each group is randomly assigned to a different activation period of the ERAS protocol. There are four activation periods, one every 3 months. However, the planned calendar and the total duration of the study have been extended by 6 months due to the COVID-19 pandemic.The expected sample size of about 2200 patients has a high statistical power (98%) to detect a reduction of LOS of 1 day and to estimate clinically meaningful changes in the other endpoints., Ethics and Dissemination: The study protocol has been approved by the Ethical Committee of the coordinating centre and by all participating centres. Study results will be timely circulated within the hospital network and published in peer-reviewed journals., Trial Registration Number: NCT04037787., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Coronavirus disease 2019 (COVID-19) pandemic has dramatically hit all Europe and Northern Italy in particular. The reallocation of medical resources has caused a sharp reduction in the activity of many medical disciplines, including urology. The restricted availability of resources is expected to cause a delay in the treatment of urological cancers and to negatively influence the clinical history of many cancer patients. In this study, we describe COVID-19 impact on uro-oncological management in Piedmont/Valle d'Aosta, estimating its future impact., Methods: We performed an online survey in 12 urological centers, belonging to the Oncological Network of Piedmont/Valle d'Aosta, to estimate the impact of COVID-19 emergency on their practice. On this basis, we then estimated the medical working capacity needed to absorb all postponed uro-oncological procedures., Results: Most centers (77%) declared to be "much"/"very much" affected by COVID-19 emergency. If uro-oncological consultations for newly diagnosed cancers were often maintained, follow-up consultations were more than halved or even suspended in around two out of three centers. In-office and day-hospital procedures were generally only mildly reduced, whereas major uro-oncological procedures were more than halved or even suspended in 60% of centers. To clear waiting list backlog, the urological working capacity should dramatically increase in the next months; delays greater than 1 month are expected for more than 50% of uro-oncological procedures., Conclusions: COVID-19 emergency has dramatically slowed down uro-oncological activity in Piedmont and Valle d'Aosta. Ideally, uro-oncological patients should be referred to COVID-19-free tertiary urological centers to ensure a timely management.

Purpose: Assuring quality of care, while maintaining sustainability, in complex conditions such as breast cancer (BC) is an important challenge for health systems. Here, we describe a methodology to define a set of quality indicators, assess their computability from administrative data, and apply them to a large cohort of BC cases., Materials and Methods: Clinical professionals from the Italian Regional Oncology Networks identified 46 clinically relevant indicators of BC care; 22 were potentially computable using administrative data. Incident cases of BC diagnosed in 2016 in five Italian regions were identified using administrative databases from regional repositories. Each indicator was calculated through record linkage of anonymized individual data., Results: A total of 15,342 incident BC cases were identified. Nine indicators were actually computable from administrative data (two structure and seven process indicators). Although most indicators were consistent with guidelines, for one indicator (blood tumor markers in the year after surgery, 44.2% to 64.5%; benchmark ≤ 20%), deviation was evident throughout the five regions, highlighting systematic overlooking of clinical recommendations. Two indicators (radiotherapy within 4 months after surgery if no adjuvant chemotherapy; 42% to 83.8%; benchmark ≥ 90%; and mammography 6 to 18 months after surgery, 55.1% to 72.6%; benchmark ≥ 90%) showed great regional variability and were lower than expected, possibly as result of an underestimation in indicator calculation by administrative data., Conclusion: Despite highlighting some limitations in the use of administrative data to measure health care performance, this study shows that evaluating the quality of BC care at a population level is possible and potentially useful for guiding quality improvement interventions.

Quality Issue: The definition of clinical pathways (CPs) and their application are heterogeneous. Each center is used to choose whether to adopt this instrument or not and to variably conceive its features We consider CPs as the necessary description of the cancer patient journey and we emphasize their role as the user view of clinical processes rather than a local translation of guidelines., Choice of Solution: We proposed a unique CPs model for all the centers of our regional network, with the aim of making CPs accountable and comparable. We also established a central quality evaluation., Implementation: Through a multi-step process, the model was proposed to the 22 Regional centers. Landmark characteristics of the project were: the involvement of hospital administrations; reference to a unique set of guidelines; a peer-review and open evaluation., Evaluation: Of the 374 expected CPs, 253 (68%) were received and evaluated. A median number of 131 items were the object of evaluation in each hub center and 77 in each spoke center. About 79.5% items were considered well described, 15.5% were absent and 5.0% partially described. The median percentage of fulfilled indicators was 85.6% in hub CPs and 82.2% in spoke CPs. Although, not all diseases were equally covered through the territory a high degree of homogeneity and a good quality of compilation were achieved., Lessons Learned: The project was shown to be feasible and achieved its goal. We suggest this process as a functional way for building uniform cancer CPs., (© The Author(s) 2019. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The present study focuses on the analysis of social, clinical and hospital characteristics that can lead to disparities in the management and outcome of care. To that end, indicators of the quality of initial treatment delivered to newly-diagnosed colorectal cancer patients in a North-Western Region of Italy, were investigated using administrative data., Methods: The cohort includes all incident colorectal cancer patients (N = 24,187) selected by a validated algorithm from the Piedmont Hospital Discharge Record system over an 8-year period (2000-2007).Three indicators of quality of care in this population-based cohort were evaluated: the proportion of preoperative radiotherapy (RT) and of abdominoperineal (AP) resection in rectal cancer patients, and the proportion of postoperative in-hospital mortality in colorectal cancer patients., Results: Among rectal cancers, older patients were less likely to have preoperative RT, and more likely to receive an AP resection compared to younger patients. The probability of undergoing preoperative RT and AP resection was reduced in females compared to males (odds ratio (OR) 0.77, 95% confidence interval (CI) 0.64-0.93 and OR 0.78, 95%CI 0.69-0.89, respectively). However, there was a trend of increasing RT over time (p for trend <0.01). The probability of undergoing AP resection was increased in less-educated patients and in hospitals with a low caseload.A higher risk of postoperative in-hospital mortality was found among colorectal cancer patients who were older, male, (female versus male OR 0.71, 95%CI 0.60-0.84), unmarried (OR 1.32, 95%CI 1.09-1.59) or with unknown marital status., Conclusions: The study provides evidence of the importance of social, clinical and hospital characteristics on the equity and quality of care in a Southern European country with an open-access public health care system.

Context: Breakthrough/episodic pain (BP-EP) diagnosis is often based on clinical experience, and different opinions exist, even among palliative care clinicians, about its definition and application to clinical practice., Objectives: The primary aim of this study was to assess the prevalence and clinical characteristics of BP-EP in an unselected Italian population of patients with cancer-related chronic pain, based on clinical diagnosis and on the use of an assessment tool, the Questionnaire for Intense Episodic Pain (QUDEI)., Methods: A cross-sectional multicenter prevalence study of 240 consecutive cancer pain patients was carried out. The physicians participating in the study attended a training session aimed at defining and recognizing BP-EP. The QUDEI, a screening and assessment tool based on patient interview, diagnosed the presence of BP-EP in patients regularly taking analgesics for the previous three days and who had at least one pain flare in the previous 24 hours. Clinical evaluation and questionnaire application were carried out by different health care providers., Results: The estimated prevalence of BP-EP was 73% (95% confidence interval [CI] = 67%, 79%) when the diagnosis was made by physicians and 66% (95% CI = 60%, 72%) when the QUDEI was applied (86% agreement). When only patients with baseline pain less than or equal to six were included in the analysis, the above prevalences decreased to 67% and 60%, respectively., Conclusion: Because BP-EP is a significant phenomenon in cancer pain management, its appropriate recognition requires a more widely, internationally accepted general definition and specific validated tools for its screening and evaluation., (Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Rationale, Aims and Objectives: Lung cancer is a disease with high consumption of health care resources. The aim of this study was to describe hospital costs due to lung cancer care from diagnosis until death or end of the study follow-up, in a cohort of incident cases, by using administrative data., Methods: Particular attention was given to the determinants of total costs and the impact of the initial treatment approach on the process of costs accumulation. Incident cases were identified by the local Cancer Registry (January 2000-December 2003) among the residents of Turin (Italy). Per patient hospital care has been determined from administrative databases (outpatient radiotherapy records and hospital discharge records). Costs determinants were identified via a multivariable generalized linear model (GLM), with a Gamma cost distribution and a logarithmic link function. To assess the time effect over the cost accumulation process for non-small-cell lung cancer cases, the same GLM Gamma model was repeated at different follow-up periods. Analyses were stratified by cancer histotype., Results: Results evidenced the relevant role of initial patterns of care on the cost accumulation process, with increased midterm costs associated with curative patterns of care., Conclusion: The use of administrative data enabled hospital lung cancer care to be described, and related costs to be estimated., (© 2010 Blackwell Publishing Ltd.)

Objective: •To provide updated figures on urinary diversion, length of stay and mortality after cystectomy in two regions of northern Italy., Patients and Methods: •Discharge records of patients undergoing cystectomy for bladder cancer in 2000-2008 were extracted from the regional archives of hospital discharges. •Data on partial vs radical cystectomy and type of urinary diversion were obtained from intervention codes. •The influence of demographic characteristics, year of intervention, presence of comorbidities and hospital cystectomy volume on the adoption of a continent diversion and on in-hospital mortality was assessed through multilevel models., Results: •The crude cystectomy rate was close to 10 per 100,000. •The share of partial cystectomies declined from 5.5% in 2000-2002 to 3.0% in 2006-2008. •A continent diversion was adopted in 35% of radical cystectomies, with higher rates in young male patients treated in high-volume hospitals. •Median length of stay declined from 20 days in 2000-2002 to 18 in 2006-2008; in-hospital mortality decreased from 3.2% to 2.2%., Conclusion: •This first population-based report on cystectomies for bladder cancer from continental Europe evidences a limited role of partial cystectomy, a high proportion of continent diversion and a decreasing trend of length of stay and in-hospital mortality., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objectives: Pain still afflicts most cancer patients, mainly in the metastatic phases, and under-treatment is well documented. Transdermal delivery systems (TDS) containing fentanyl or buprenorphine could potentiality have advantages over oral and parenteral routes, but evidence from comparative trials are scanty. In the framework of a wider initiative, an Outcome Research Study was carried out in Italy in 2006 to evaluate the effects of various analgesic options, particularly buprenorphine TDS., Methods: This is a multicenter, open-label, prospective, nonrandomized study. Data were collected using a web-based standardized system, with a follow-up up of to 3 months. Pain intensity, the primary outcomes of the study, was measured using 11-point numerical rating scales from the Brief Pain Inventory., Results: One-hundred ten centers recruited 1801 cases, most of which (60%) were receiving a strong opioid at the time of inclusion. Of these, 257 had TDS buprenorphine as first choice. Of the remaining 709 patients who at the time of inclusion were not on a strong opioid, 325 changed to a strong opioid and in 43% it was TDS buprenorphine. During the follow-up, physicians had to increase the dosage to control pain (average increase between 16% and 17%). About 34% of patients had an improvement of at least 2 points in worst pain, 15% had a 20% improvement in pain relief, and 40% in satisfaction. Results were in line with those of patients receiving other World Health Organization-level III opioids., Conclusions: Despite the limitations owing to the observational design, these findings may be useful to clinicians to judge the value of the drug under evaluation better and to help researchers design further comparative studies.

Purpose: No structured modality for providing information and support to patients in oncology wards has been validated in clinical trials., Methods: This is a pragmatic, two-arm, cluster randomized trial, with the oncology ward as random assignment unit. Centers were allocated to implement a Point of Information and Support (PIS) or to a control group. The PIS included a library for cancer patients and a specifically trained oncology nurse. End points, measured at patient level, were psychological distress and satisfaction with received information. Both intent-to-treat and per-protocol analyses considering clustering were performed., Results: Thirty-eight Italian cancer centers were randomly assigned, and 6 months after PIS creation, 3,286 unselected, consecutive cancer patients were surveyed (1,654 in the experimental group and 1,632 in the control group). Three thousand one hundred ninety-seven (97%) questionnaires were collected and deemed valid. Fifty-two percent of centers (11 of 21 centers) in the experimental arm did not implement the PIS in accordance with the protocol. Overall, 34% of patients showed moderate to severe psychological distress, and only 9% declared dissatisfaction. Intent-to-treat analysis did not yield significant differences. Although the per-protocol analysis did show a reduction in psychological distress (28.9% for functioning PIS v 33.3% for no PIS) and dissatisfaction (6.4% for functioning PIS v 9.3% for no PIS), differences did not reach significance., Conclusion: This is the first cluster randomized trial aiming to demonstrate that a structured modality of providing information reduces psychological distress. We did not find this, but we believe results should be interpreted cautiously, particularly because of the low compliance with PIS implementation. Context analysis preceding such interventions is essential.

Background: Advance directives, acceleration of death, euthanasia and 'life-sustaining treatment' have sparked much heated debate among the media, the public, doctors and political leaders. We evaluate the personal opinions of Italian Association of Medical Oncology (AIOM) members., Patients and Methods: A 30-item questionnaire was developed and delivered to all 1,832 AIOM members., Results: Six-hundred and eighty-five (37%) oncologists completed and returned the questionnaires. Sixty-three per cent felt culturally and psychologically prepared to face these issues. Fifty-four per cent believed that what had been decided while the patient enjoyed good health is no longer applicable in an advanced state of terminal illness. Thirty-nine per cent believed that doctors should abide by these directives, while 49% believed that this should be discussed on a case-by-case basis. Fourteen per cent of oncologists were favourable towards euthanasia and 42% only in particular circumstances. Fifty-six per cent had received at least one request for accelerating death: 15% consented, 50% discussed it with the patient and 31% refused., Conclusion: Advance directives, euthanasia, accelerated death and life-sustaining treatment represent considerable challenges for Italian oncologists. Although prepared to face these issues, AIOM members ask for a debate within the medical world and for a shared judicial regulation.

Background and Objective: In the recent X-ACT (Xeloda in Adjuvant Colon cancer Therapy) trial, oral capecitabine (Xeloda) demonstrated superior efficacy and an improved safety profile compared with infused fluorouracil + leucovorin (folinic acid) [FU+LV] in patients with Dukes' C colorectal cancer. We used the X-ACT results to determine the cost effectiveness of capecitabine compared with FU+LV from the perspective of the Italian National Health Service (NHS)., Methods: Medical resource use data were collected throughout the treatment period. Unit costs for drug administration, hospitalization, emergency room visits and concomitant medications were obtained using Italian published sources. A health-state transition model was used to estimate the incremental cost-effectiveness ratio per quality-adjusted life-month (QALM) gains in the intent-to-treat population (1004 and 983 patients in the capecitabine and FU+LV arms, respectively). Costs and effectiveness were discounted at 3.5%. Costs were calculated in euros (2005 values)., Results: Administration of capecitabine required fewer clinic visits per patient than FU+LV (7.35 vs 28.0, respectively). Mean acquisition costs per patient for capecitabine were higher than for FU+LV (euro 2533 vs euro 231, respectively), but this difference was offset by the difference in mean chemotherapy administration costs per patient for FU+LV (euro 4338, compared with euro 152 for capecitabine). Mean total hospital days and medication costs for treatment-related adverse events were higher for FU+LV than for capecitabine (euro 352 vs euro 78, respectively). The cost of emergency room visits for the treatment of adverse events did not differ between the treatment groups. With respect to the lifetime horizon, compared with FU+LV, capecitabine is projected to increase QALMs by a mean 6.5 months, with overall cost savings of euro 2234 over the treatment period. These findings show that capecitabine is an economically dominant treatment in this setting., Conclusions: Adjuvant capecitabine for patients with Dukes' C colon cancer has the same activity in terms of outcome when compared with FU+LV but is a lower cost option from the economic perspective of the Italian NHS.

Objectives: This phase 2 randomized study compared the toxicity and assessed the efficacy of gemcitabine-cisplatin (GP) and gemcitabine-carboplatin (GC) in patients with advanced transitional cell carcinoma of the urothelium (TCC), with the main objective to demonstrate a reduction in toxicity of at least 25% in the GC arm., Methods: A total of 110 chemonaive patients (55 per arm) with locally advanced or metastatic TCC received gemcitabine 1250 mg/m(2) on days 1 and 8 plus cisplatin 70 mg/m(2) on day 2 (GP) every 3 wk or gemcitabine 1250 mg/m(2) on days 1 and 8 plus carboplatin AUC 5 on day 2 (GC) every 3 wk for a maximum of six cycles., Results: No differences between arms were noted in the overall toxicity profiles and any parameter of toxicity. The most frequent grade 3-4 hematologic toxicity was neutropenia in 34.6% of patients for GP and 45.4% for GC. The most frequent grade 3-4 nonhematologic toxicity was nausea and vomiting (GP: 9.1%; GC: 3.6%). Grade 1-2 nephrotoxicity occurred in 14 GP-treated patients (26.0%) and 9 GC-treated patients (16.3%). Per an intent-to-treat analysis, overall response, evaluated on 80 patients, was 49.1% for GP (CR: 14.5%; PR: 34.5%) and 40.0% for GC (CR: 1.8%; PR: 38.2%). Median time to progression was 8.3 mo for GP and 7.7 mo for GC. Median survival was 12.8 mo and 9.8 mo for GP and GC, respectively., Conclusions: GC has a comparably acceptable toxicity profile compared with that of GP and seems active in patients with TCC.

Objective: To develop a method for adapting the best available cancer practice guidelines (CPGs) to the regional oncology network in Piedmont (NW of Italy, with about 4.3 million residents)., Methods: Four CPG were developed by multidisciplinary working groups, involving local opinion leaders, coordinated by the same team (including epidemiologists and health economists). The major features of these guidelines were: (a) to cover all the phases ofthe disease (from diagnosis to palliative care); (b) to satisfy common standards for evidence based guidelines; (c) to be coherent with the local health organization and resource availability. In the first three CPGs, regarding common cancers (colon-rectum, breast, lung), recommendations were graded according to the underlying level of evidence, from A to C, and treatment was organized by specialty. In the last guideline, regarding a rare condition (soft tissue sarcomas, STS), a grading system reflecting also the clinical importance of the decision was adopted and treatment recommendations were organized by clinical scenarios. In each guideline, some implementation tools, including a set of process and outcome indicators for audit monitoring, were provided., Results: The four CPGs have been published between 2001 and 2004. The number ofrecommendations ranged between 38 (STS) and 103 (colon-rectum), with some differences in the distribution by specialty and grading. The CPGs have been disseminated through the oncology network and local health coordinators have been involved in the implementation. The impact of the CPGs is being evaluated by different approaches (analyses of administrative data, sample surveys and user's interviews)., Conclusions: To adapt evidence based guidelines to a specific regional health organization is feasible and may be usefil for diseases requiring a multidisciplinary approach and continuity of care.

Background: Management of pain related to advanced or metastatic cancer, although the availability of several pharmacological and non-pharmacological interventions and the existence of well-known guidelines and protocols, is often difficult and inadequate. Evidence of the relative effectiveness of current options for treating cancer pain from comparative randomized studies is scanty., Methods: In the context of a wider project, a multicenter, open label, prospective Outcome Research study will be launched in Italy in 2006 to investigate the epidemiology of cancer pain and of its treatments, the quality of analgesic-drug therapy and the effectiveness of alternative analgesic strategies in a large, prospective, unselected cohort of cancer patients using the state-of-the art of patient-reported-outcomes. About 100 Italian centers will recruit 2500 patients with advanced/progressive/metastatic cancer with pain (related to the cancer disease) requiring analgesic treatments. Each center is expected to recruit 25 consecutive and eligible patients during the study inception period. Approximately two months will be allowed for subject recruitment and enrollment. Subject evaluation and follow-up will be for 3 months. The effect on outcomes of various therapeutic analgesic options administered by physicians, given the observational approach where patients are not assigned at random to different treatments, will be compared using the propensity score approach, allowing the adjustment for treatment selection bias. Later, after the launch of the observational study and on the basis of results, in specific subsamples of patients and in select centers of the network, a Randomized Controlled Trial will be carried out to formally compare the efficacy of alternative analgesic strategies, with particular emphasis on oral morphine (as comparator) and buprenorphine patch (as experimental arm). Results from the outcome (cohort) and experimental (Randomized Controlled Trial) studies will ensure both the external and internal validity.

Paclitaxel is now included in second- and even first-line regimens in advanced breast cancer. The optimal dose and schedule of this drug, however, still remain a matter of investigation. A group of 57 consecutive patients with advanced breast cancer previously treated with anthracycline-containing regimens were submitted to treatment with single-agent paclitaxel administered at 130 mg/m2 on days 1 and 8 every 21 days. Of the 57 patients, 56 were fully evaluable, and of these 25 had an absolute anthracycline resistance, 14 a relative resistance and 17 were potentially sensitive. The median age of the patients was 57 years (range 33-71 years), their median performance status was 1 (0-3), and 27 (47%) had liver involvement, 17 (30%) lung involvement, 30 (53%) bone involvement and 15 (26%) skin/lymph node involvement. Toxicity was recorded in 295 cycles. This scheme was well tolerated, the dose-limiting toxicities being hematological and neurological. Grade 3/4 leukopenia was observed in 20% of patients at nadir, while grade 3 leukopenia was observed in 3% of patients at recycle. Only one patient experienced febrile neutropenia. Grade 2/3 neurotoxicity was observed in 26% of patients, leading to drug withdrawal in three. The treatment was given on an outpatient basis in all patients and the median relative dose intensity of 86.6 mg/m2 per week was 100% of the planned dose (range 75-100%). Three patients (5%) attained a complete clinical response and 12 (21%) a partial response for an overall response rate of 26% (95% confidence interval 18-38%), while 30 (53%) attained disease stabilization and 11 progressed (19%). Time to progression in responding patients was 10.3 months, and the median overall survival of the entire population was 15.4 months. To conclude, paclitaxel administration on days 1 and 8 every 21 days was active and manageable in advanced breast cancer patients previously treated with anthracyclines. The response obtained was durable.

A transient rise in serum alkaline phosphatase (ALP) activity (ALP flare) after androgen deprivation in prostate cancer patients with bone metastases has been previously correlated with both response to therapy and poor prognosis. In the present study we analyzed data coming from an Italian multicenter phase III, trial aimed to compare the efficacy of treatment with goserelin alone with that of goserelin plus mitomycin C. Sixty-seven bone metastatic patients were enrolled: 32 were treated with goserelin and 35 with and goserelin plus mitomycin. 58 cases had ALP measured every month; and were considered for flare assessment. Remarkably elevated ALP and PSA levels at baseline were significantly correlated with poor prognosis. The addition of mitomycin to goserelin resulted in a greater percent reduction of PSA values with respect to goserelin alone but did not augment the time to progression and overall survival. The monthly profile of ALP serum levels was superimposable in patients assigned to hormone therapy or chemotherapy plus hormone therapy. Patients showing a flare in ALP activity (transient rise > 15% in ALP values with respect to baseline at the first month) were classified as responders to therapy or as having stable disease upon PSA evaluation and/or at bone pain assessment, but had a shorter time to progression (median 12 months) in comparison to those showing a different ALP pattern (median 23 months). The measurement of flare in ALP activity during androgen suppression with or without concomitant mitomycin administration, may permit the early identification of patients who are likely to progress rapidly, and hence be candidate for more aggressive treatments.