Sequential chemotherapy with carboplatin followed by weekly paclitaxel in advanced ovarian cancer: results of a multicenter phase II study of the northeastern German society of gynecological oncology.

BACKGROUND: For the adjuvant setting of advanced ovarian cancer (AOC) after primary radical surgery the combination of paclitaxel and platinum in a 3-week schedule has emerged as the current standard. In preclinical studies additional anti-angiogenic effects of low dose paclitaxel infusion were demonstrated. A sequential schedule of carboplatin and paclitaxel has the potential to improve the therapeutic index. METHODS: In this multicenter phase II trial four cycles of carboplatin at a dose of AUC 5 (d1/q21d) followed by 12 cycles of weekly paclitaxel at a dose of 80 mg/m(2) (d1/q7d) were applied after primary radical surgery. Eligible were all optimally or sub-optimally debulked patients with FIGO IA-IV ovarian cancer. All patients with hemoglobin levels <12 mg/dl received erythropoietin additionally. RESULTS: Between July 2003 and May 2005, 105 patients from 27 institutions were enrolled. The median age was 60 years (range: 23-80 years). A median number of 16 courses (range 1-16) were applied. The incidence of non-hematological toxicities was very low. Only 41% of patients experienced alopecia (grade 1-2). Neurotoxicity (grade 3-4) was not observed. Grade 3-4 hematological toxicity (43% of all patients) included thrombocytopenia (17%), anemia (3%), leucopenia (23%), and neutropenic fever (0%). Ninety-seven percent received erythropoietin. Thromboembolic events (4%) were not increased in patients who received erythropoietin. After a median time of 23 months (range: 1-42 months) 32 patients had died, and the median overall survival was not reached. The progression-free survival was 25.4 months (95% CI: 18.8-40+). CONCLUSION: 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.

Pegylated liposomal doxorubicin (CAELYX) in patients with advanced ovarian cancer: results of a German multicenter observational study.

PURPOSE: Pegylated liposomal doxorubicin (PLD, CAELYX) has demonstrated activity in several phase-III trials and has been approved for the therapy of relapsed ovarian cancer after platinum treatment. Aim of this observational study was to analyze the efficacy and toxicity profile of PLD under routine clinical conditions and without the general restrictions of defined inclusion and exclusion criteria of clinical trials. METHODS: Between 2003 and 2005, a total of 190 patients with relapsed ovarian cancer were enrolled. 183 patients were available for evaluation; dose-intensity, modifications, treatment duration, toxicities and response were systematically analyzed. RESULTS: The median patient age was 62 years (range 23-86 years). 45.4% of the patients received PLD as second-line therapy and a median of four courses per patient were administered. The median dose of PLD was 40 mg/m(2), most frequently used every 4 weeks (68.8%). Grade 3 Leucopenia (1.6%) and grade 3 and 4 thrombocytopenia (0.5%) were the most frequent hematological toxicities. The most frequent non-hematological toxicities were skin toxicity, pain and nausea, which were observed in 38.8, 41 and 45.9% of the patients, respectively. Twenty-seven percent of the patients showed a response to therapy with 6.9% achieving complete remission and 20.1% achieving partial remission. 37.7% achieved a stable disease. The median duration of response for all patients was 4.8 months (range 0-51.8 months). Median progression-free interval and overall survival were 5.8 months (95% CI 5.1-6.6 months) and 16.6 months (95% CI 13.9-22.6 months), respectively. CONCLUSIONS: PLD is safe and effective in patients with relapsed ovarian cancer, even after numerous previous treatment regimens. A dose of 40 mg/m(2) every 28 days seems to be an effective and well-tolerated therapeutic option in advanced ovarian cancer with a low incidence of hematological toxicities and acceptable non-hematological toxicities.