15062 Background: Patients (pts) with newly diagnosed AOC generally receive platinum plus taxane therapy. G represents a new active agent to improve the standard regimen. To investigate the safety of two schedules of induction treatments both followed by triplet PCG we have drafted a phase II study. Methods: 14 pts, suboptimally debulked (FIGO stage IIIc) entered the study. HDC ( AUC 7,5) was administered for 2 courses every 21 days ( arm A) and P ( 80 mg/sqm, d 1,8,15,22) + G ( 2500 mg/sqm, d 1,15) (arm B). Both regimens have been followed by standard triplet P ( 175 mg/sqm, d1) + C ( AUC 5, d1) + G ( 800 mg/sqm, d1,8) every 21 days for a total of 6 courses. Antiemetics, corticoids, antihistaminics and ranitidine have been added. Results: The median age was 57 y (39–68). Histology was serous in 64.3%, mixed 14.3% and other 21.4%. All pts had Grade 3 tumor but one. Seven pts received arm A schedule and 7 arm B both followed by PCG regimen. Worst haematological toxicities ( in term of nadir) observed in all courses for all pts were neutropenia G4 ( 42.8% arm A vs 71.4% arm B), anemia G2 (71.4% arm A vs 57.1% arm B), thrombocytopenia G2 ( 57.1% arm A vs 42.8% arm B). Most common non haematological toxicities were alopecia and mild nausea/vomiting. Mild paresthesias in both regimens were observed. No sepsis or neutropenic fever nor unespected toxicity or treatment-related deaths were observed. 71.4% of pts completed foreseen schedules of treatments. 78.5% of pts received erytropoietin and 28.5% G-CSF support. Conclusions: HDC and weekly PG followed by triplet PCG are feasible and safety regimens in AOC pts ( residual disease > 1 cm). Further phase II-III setting study using these schedules will be conducted. No significant financial relationships to disclose.

OBJECTIVE:The purpose of this study was to define the maximum tolerated dose (MTD) of topotecan given as escalating doses combined to a fixed dosage of carboplatin in late relapsing ovarian carcinomas.METHODS:Women with relapsing ovarian cancer more than 6 months after first-line treatment were eligible for the study. In the first phase of the trial, patients were allocated to escalating topotecan doses with a carboplatin fixed dose (AUC 5, according to Cockcroft's formula). If no "severe" adverse event occurred in 1 or more of the patients, the topotecan dose was increased. The starting dose of topotecan was 0.50 mg/m(2)/day, for 3 consecutive days, and the dose step was of 0.25 mg/m(2)/day, till 1.5 mg/m(2)/day. The study progressed then in a phase II trial.RESULTS:A total of 39 patients entered the trial. Twenty took part in the escalating topotecan dose phase (4 per dose level, 0.50, 0.75, 1, 1.25, and 1.50 mg/m(2)/day) and 19 in the phase II. No severe adverse event was observed in the phase I of the trial, so the MTD was not reached. In the phase II trial topotecan was given to 1 mg/m(2)/day. Overall grade 3-4 neutropenia, lasting 7 days or less, was observed in 58.9% (23 patients). Thrombocytopenia occurred in 30.8% (12 patients) and grade 3 anemia in 25.6% (10 patients) of subjects. No life-threatening event occurred. Platelets or red blood cell transfusions were given in three cases (7.8%).CONCLUSIONS:This daily-times-3-day schedule of topotecan in combination with carboplatin is safe.

AIMS AND BACKGROUND:To evaluate the toxicity of high-dose ifosfamide in ovarian cancer patients refractory or resistant to platinum and/or paclitaxel-containing chemotherapy.METHODS:This was an open, non-randomized phase I-II trial of high-dose ifosfamide. Eligibility criteria were: patients aged 18-75 years affected by ovarian cancer with refractory or resistant disease or early relapse after first-line treatment including platinum or paclitaxel. Three patients were given escalating ifosfamide doses; if no severe adverse events occurred, the ifosfamide dose was increased. The starting dose of ifosfamide was 10 g/m2 i.v. and the dose increase was 1 g/m2 every four weeks for a total of five courses; 12 g/m2 was the maximum ifosfamide dose to be administered. The trial then progressed to a phase II trial, in which ifosfamide was given at the maximum tolerated dose reached during the escalating dose phase.RESULTS:A total of 36 patients entered the trial. Nine patients were involved in phase I of the study; 3 received 10 g/m2 ifosfamide, 3 11 g/m2 and 3 12 g/m2. Of the 32 evaluable patients 6 (18.8%) achieved a complete response and three (9.4%) a partial response, giving an overall response rate of 28.1% (95% CI, 15-61% based on Poisson's approximation). The median number of ifosfamide courses was five. G1, G2 and G3 neurotoxicity was reported in 3 (8%), 2 (5%) and 2 (5%) patients, respectively.CONCLUSION:This phase I-II trial indicates that high-dose ifosfamide has some activity but also a relevant degree of toxicity in resistant or refractory platinum and paclitaxel-pretreated ovarian cancer.