Sequential therapy with carboplatin (C) followed by paclitaxel (P) as first-line chemotherapy in 105 patients with advanced ovarian cancer (AOC): Results of a multicenter phase II study of the Northeastern German Society of Gynecological Oncology

Abstract

5533 Background: For the adjuvant setting of AOC after primary radical surgery the combination of paclitaxel and platinum in a three weeks schedule has emerged as the current standard. Exposition duration of the drug is important for cell death. In animal model additional anti-angionetic effects of low dose paclitaxel infusion was observed. A sequential schedule of these agents can potentially yield in an improved therapeutic index. Methods: In this multicenter-phase II trial after primary radical surgery 4 cycles of Carboplatin at a dose of AUC 5 (d1/q21d) followed by 12 cycles weekly paclitaxel at a dose of 80mg/m2 (d1/q7d) was applied. All patients with haemoglobin levels < 12mg/dl get primary erythropoietin. No primary use of other growth factors were allowed. Eligibility criteria were: AOC (FIGO IIb-IV), ECOG performance status 0–2, normal organ functions. Results: Between 07/2003 and 05/2005, 105 patients from 27 institutions were enrolled. The median age was 60 years (23–80). FIGO-stages were: II: 11.4%, III: 67.6%, IV: 14.2%. 1,441 cycles were analyzed and in median 16 courses were applied (range 0–16). The incidence of non-hematological toxicities was very low. 25 % of all patients experienced alopecia (grade 1–2). Neurotoxicity and nausea/vomiting (grade III-IV) occurred in no patients. Grade 3–4 hematological toxicity (% of all pts) included: thrombocytopenia (16 %), anemia (3%), leucopenia (22%), neutropenic fever (0%). 96% received erythropoietin. Thromboembolic events (5%) were not increased in patients who received erythropoietin. After a median follow-up interval of 10 months (range: 1–27 months) 20 patients died, the median overall survival is already not reached. The progression free survival is 19 months (range:10–23 months). Conclusions: These results suggest that this sequential regimen using weekly paclitaxel represents an efficacious and well-tolerated regimen. A randomized study comparing this new schedule with the conventional 3-week protocol is warranted. (Supported by Bristol Myers Squibb Germany and Ortho Biotech Germany) No significant financial relationships to disclose.