Rationale and delineation of a composite index of relative antitumoural efficacy (In-RATE).
ABSTRACT Over the last decades, the development of new drugs has allowed cancer patients to experience several lines of chemotherapy, the objective of which is a long term stabilization of the tumour. The objectives of this work was to delineate a composite index of relative antitumoural efficacy (In-RATE) of a regimen over another, including response rate (RR), median time to progression (TTP) and progression rate (PR). When considering two treatments a and b, the In-RATE was defined as RRa/RRb x TTPa/TTPb x PRb/PRa. Values significantly superior or inferior to 1 reveal an advantage for treatment a or b, respectively. The applicability of the In-RATE to published randomized trials in four frequent tumour types (colorectal, non-small cell lung, advanced ovarian and metastatic breast cancers) was suggested to more precisely distinguish the effects of different drugs, and sometimes to detect a significant difference when the published data did not conclude to statistical difference.
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ABSTRACT: The aim of this phase II study was to assess the benefits of a weekly administration of topotecan and gemcitabine in patients with ovarian carcinoma having relapsed after platinum/taxane-based first-line chemotherapy. Seventy-seven patients with progression of disease </=12 months after first-line chemotherapy were enrolled to receive topotecan (2.5 mg/m(2)) and gemcitabine (1000 mg/m(2)) on days 1, 8 and 15 (q 28 d). Primary endpoint was the response rate. Stabilization rate and symptom improvement were also assessed. All patients received the combination and 66 were evaluable (>/=2 cycles administered). The only major severe toxicity was neutropenia grades 3 (17%) and 4 (6%). Approximately 60% of the patients received the complete schedule of treatment, dose interruptions/delays being mainly due to moderate thrombocytopenia or neutropenia. The objective response rate was 14%, the values for patients having relapsed within 6 (n=30) and 6-12 (n=36) months being 7% and 20%, respectively. Median durations of response were 4.9 and 6.4 months and clinical benefit rates including stabilizations reached 63% and 69% in patients having relapsed within 6 or 6-12 months, respectively. Corresponding median overall survival was 7.5 and 15.6 months. Symptoms and pain were reduced in 64% and 39% of the patients concerned, respectively. In early relapse ovarian cancer, weekly combination of gemcitabine and topotecan has a modest objective response rate. However, a high proportion of patients experienced stable disease and symptom control leading to acceptable quality of life.Gynecologic Oncology 09/2009; 115(3):382-8. · 3.93 Impact Factor
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ABSTRACT: Topotecan is indicated in the treatment of advanced-stage ovarian cancers refractory to prior platinum-based regimen. The aim of this study was to compare the standard therapeutic strategy with a novel strategy of weekly administration of topotecan. The primary endpoints were dose density and overall tolerance. This retrospective cohort study included patients with ovarian cancer in relapse. During a first period (1998-2001), 24 patients received the standard topotecan dose of 1.5 mg/m(2)/day for 5 consecutive days with a 3-week interval between each treatment course. During a second period (2003-2006), 21 patients received a weekly topotecan dose of 4 mg/m(2) for 3 weeks out of every 4. Grades III and IV haematological toxicities were more frequent with the standard strategy (p < 0.05), even after adjustment of the prescription of erythropoietin and G-CSF. With the weekly strategy, an increase in dose density and a reduction in the number of delayed doses were observed. No significant difference between the 2 strategies was found in terms of response to the treatment and specific survival. This study suggests that the weekly administration of topotecan 4 mg/m(2), for 3 weeks out of every 4, results in a better maintenance of dose density and a reduction in haematological toxicity.Oncology 01/2007; 73(3-4):177-84. · 2.17 Impact Factor