Search

Progression-free survival (PFS), the time from registration or randomisation of a patient until objective disease progression or death, can be considered as an outcome for clinical research and also as a basis for regulatory approval. Current experience suggests that greater standardisation and consistency are needed for clinical trials utilising PFS endpoints. To this end, the Biotherapy Development Association (BDA) convened a breakout session on the topic of PFS during its Third Alpine Meeting held 14–16 March 2007. Representatives of the pharmaceutical industry, regulatory agencies, academia, and patient advocacy groups identified challenges, developed recommendations, and worked to build consensus regarding the conduct of clinical trials utilising PFS as an end-point to help speed new targeted biologics to the patient bedside.

BACKGROUND: No differences in response rate (RR), progression-free survival (PFS), overall survival (OS) and quality of life (QoL) were seen in patients randomly treated with biweekly oxaliplatin plus either fluorouracil/folinic acid or capecitabine. METHODS: We investigated the independent effect of baseline clinical characteristics and physical functioning (PF) domain on RR, PFS, and OS in 310 patients who completed the EORTC QLQ-C30 questionnaire. Multivariate analyses stratified by treatment were performed. An exploratory analysis was done by grouping patients with a PF score superior or equal to the highest quartile (n = 111), included between the highest and the lowest quartiles (n = 99), or inferior to the lowest quartile (n = 100). The relationship between these three groups and the ECOG PS was then analysed. RESULTS: At multivariate analysis, OS was negatively affected by the number of metastatic sites, the serum alkaline phosphatase, and the ECOG PS, while it was positively affected by the previous surgical resection of the primary tumour. Adding the baseline PF score, the number of disease sites (p < 0.0001), the serum alkaline phosphatase (p = 0.0057), and the PF (p = 0.0007) retained an independent significance, while the ECOG PS and the previous surgery were no longer significant. PF did not significantly affect PFS or RR. A good but not totally overlapping correlation was found between PF grouping and ECOG PS score. CONCLUSIONS: Baseline self-reported PF independently predicted the OS of patients. Assessment of QoL should be incorporated in randomised trials evaluating the management of patients with MCRC.

PURPOSE: Oxaliplatin combined with either fluorouracil/leucovorin (OXAFAFU) or capecitabine (OXXEL) has a demonstrated activity in metastatic colorectal cancer patients. We aimed at comparing these two regimens in terms of response rate (RR), safety, progression-free survival (PFS), and quality of life (QoL) of patients. METHODS: A total of 322 patients with metastatic colorectal cancer were randomized to receive biweekly: oxaliplatin 100 mg/m(2) i.v. on day 1, capecitabine 1,000 mg/m(2) orally twice daily from day 1 to day 11 (OXXEL); or oxaliplatin 85 mg/m(2) i.v. on day 1; 6S-leucovorin 250 mg/m(2) i.v. and fluorouracil 850 mg/m(2) i.v. on day 2 (OXAFAFU). RESULTS: Eleven complete and 42 partial responses were registered with OXXEL (RR = 34%); six complete and 48 partial responses were obtained with OXAFAFU (RR = 33%) (P = 0.999). Severe adverse events were less frequent (32 vs. 43%) with OXXEL, which also reduced the occurrence of severe neutropenia (10 vs. 27%) and febrile neutropenia (6 vs. 13%), but produced more gastric side effects (8 vs. 3%) and diarrhea (13 vs. 8%). QoL did not differ across the two arms. Median PFS was 6.6 months in the OXXEL, and 6.5 months in the OXAFAFU arm (HR = 1.12, P = 0.354). Median overall survival was 16.0 and 17.1 months (HR = 1.01, P = 0.883). CONCLUSIONS: OXXEL and OXAFAFU regimens were equally active in metastatic colorectal cancer. The choice should be based on patient preference and on pharmacoeconomic evaluations.

Laura Palmeri, Marina Vaglica, Sergio PalmeriDepartment of Oncology, University of Palermo, Palermo, ItalyAbstract: Breast cancer is the most frequent tumor among women worldwide and is the second cause of cancer-related mortality in the US. Metastatic breast cancer (MBC) accounts for less than 10% of newly diagnosed breast cancer patients and about 30% of early breast cancer patients will develop recurrent, advanced, or metastatic disease. It remains an incurable illness and the primary goal of its management is palliative. Several agents are active for the first-line treatment of MBC. The taxanes, paclitaxel and docetaxel, represent the standard of care for the treatment of these patients. Among the various schedules, docetaxel can be administered weekly, achieving similar efficacy results with lower toxicity compared with conventional schedules. Weekly docetaxel (25–40 mg/m2) has been widely tested in several phase I and II studies both as a single agent and in multichemotherapy regimens, reaching overall response rates ranging from 26% and 86% or 20% and 73% with docetaxel alone or in combination, respectively, depending on doses, associations, and line of treatment. Overall, published data support the administration of weekly docetaxel for the treatment of MBC patients even if data from phase III randomized trials are still lacking.Keywords: docetaxel, weekly, metastatic breast cancer, chemotherapy

The aim of this national cross-sectional survey was to draw information on pain prevalence and intensity from a large sample of patients who were admitted to oncologic centres for different reasons and to evaluate the pain treatment and possible influencing factors.A total of 2,655 patients completed the study. Nine hundred and one patients (34%) reported pain.Higher pain levels were observed in inpatients, in the presence of bone metastases, and with low levels of Eastern Cooperative Oncology Group status. The number of patients receiving strong opioids increased with the highest levels of pain. However, a significant part of patients with moderate-severe pain were not receiving appropriate medication, patients being predominantly administered non-opioid drugs. General practitioners' attitudes did not negatively influence the opioid prescription.The results of this survey indicate a need for continuing educational and informative program in pain management for oncologists and more generally for any physician dealing with cancer patients.

We retrospectively assessed tolerability and efficacy of paclitaxel plus gemcitabine combination in 259 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) enrolled in three randomized SICOG trials according to their age (70 years) at study entry. Apart from age, demographic and clinical characteristics were similar in the two groups. Response rate of paclitaxel plus gemcitabine was similar in younger and in elderly (36% versus 30%). Chemotherapy was well tolerated, but severe neutropenia (12% versus 7%), anaemia (6.6% versus 1.8%), and vomiting (5% versus 0) were more frequent in elderly patients. Both median progression-free survival (PFS, 5.5 months versus 4.2 months), and overall survival (OS, 11.1 months versus 9.1 months) resulted slightly prolonged for younger patients. However, only stage and performance status resulted independently affecting PFS and OS. In conclusion, paclitaxel plus gemcitabine were similarly tolerated and active in younger and elderly patients. This regimen should be considered an option for the management of fit elderly patients.

BACKGROUND: Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations. PATIENTS AND METHODS: Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m(2) and VNR 25 mg/m(2) on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m(2) and PTX 125 mg/m(2) on days 1 and 8 (GT arm); (iii) GV plus CDDP 50 mg/m(2) on days 1 and 8 (PGV arm); and (iv) GT plus CDDP 50 mg/m(2) on days 1 and 8 (PGT arm). Treatments were repeated every 3 weeks for a maximum of six cycles. RESULTS: A total of 433 (stage III, 160; stage IV, 273) patients were randomly allocated to the study. RR was 48% [95% confidence interval (CI), 42% to 54%] for triplets and 35% (95% CI, 32% to 38%) for doublets (P = 0.004). Median progression-free survival (6.1 versus 5.5 months, P = 0.706) and median OS (10.7 versus 10.5 months, P = 0.379) were similar. CDDP significantly increased the occurrence of severe neutropenia (35% versus 13%), thrombocytopenia (14% versus 4%), anaemia (9% versus 3%), vomiting (6% versus 0.5%), and diarrhoea (6% versus 2%). Conversely, frequency of severe neutropenia (30% versus 17%) and thrombocytopenia (11% versus 6%) was significantly higher with VNR-containing regimens. CONCLUSIONS: Adding CDDP to GV or GT significantly increased RR, but did not prolong the OS of patients. Among doublets, the GT regimen should be preferred in view of its better safety profile.

BACKGROUND: : To date, the standard treatment for patients who have carcinoma of unknown primary site has not been established. METHODS: : In this randomized Phase II study, 66 previously untreated patients (33 patients per arm) with carcinomas of unknown primary site received cisplatin (35 mg/m2) and gemcitabine (1000 mg/m2) with either paclitaxel (70 mg/m2) or vinorelbine (25 mg/m2), and all drugs were administered intravenously on Days 1 and 8 of a 21-day cycle. Twenty-nine patients (44%) presented with > or =2 involved sites. The pathologic diagnosis was mainly adenocarcinoma (48 patients; 72.7%) and squamous carcinoma (7 patients; 10.6%). RESULTS: : In the first arm, 16 patients (48.5%) experienced an objective response, and 9 patients (27.2%) had disease stabilization. In the vinorelbine-containing arm, 14 patients (42.3%) experienced an objective response, and 8 patients (24.2%) had disease stabilization. The median response duration and the median time to progression were similar in both treatment arms; the median overall survival was 9.6 months (95% confidence interval, 7.11-12.09 months) for patients who received the cisplatin/gemcitabine/paclitaxel regimen and 13.6 months (95% confidence interval, 6.61-20.59 months) for patients who received the vinorelbine combination. Grade 3 and 4 toxicities were more frequent in the paclitaxel-containing arm. CONCLUSIONS: : Both combinations satisfied the 2-step design, demonstrating antitumor activity without relevant differences in response rates or response duration; however, the vinorelbine-containing regimen yielded superior results both in terms of overall survival (13.6 months vs 9.6 months) and in terms of treatment tolerability. Therefore, according to a pick the winner attitude, the combination of cisplatin/gemcitabine/vinorelbine may be considered in the design of future randomized, Phase III trials for patients with carcinomas of unknown primary site.