Gemcitabine-oxaliplatin combination for ovarian cancer resistant to taxane-platinum treatment: a phase II study from the GINECO group.

Advanced ovarian carcinoma in early progression (<6 months) (AOCEP) is considered resistant to most cytotoxic drugs. Gemcitabine (GE) and oxaliplatin (OXA) have shown single-agent activity in relapsed ovarian cancer. Their combination was tested in patients with AOCEP in phase II study. Fifty patients pre-treated with platinum-taxane received q3w administration of OXA (100 mg m(-2), d1) and GE (1000 mg m(-2), d1, d8, 100-min infusion). Patient characteristics were a : median age 64 years (range 46-79),and 1 (84%) or 2 (16%) earlier lines of treatment. Haematological toxicity included grade 3-4 neutropaenia (33%), anaemia (8%), and thrombocytopaenia (19%). Febrile neutropaenia occurred in 3%. Non-haematological toxicity included grade 2-3 nausea or vomiting (34%), grade 3 fatigue (25%),and grade 2 alopecia (24%). Eighteen (37%) patients experienced response. Median progression-free (PF) and overall survivals (OS) were 4.6 and 11.4 months, respectively. The OXA-GE combination has high activity and acceptable toxicity in AOCEP patients. A comparison of the doublet OXA-GE with single-agent treatment is warranted.

Intensified dose of cyclophosphamide with G-CSF support versus standard dose combined with platinum in first-line treatment of advanced ovarian cancer a randomised study from the GINECO group.

ICON3 trial results have suggested that CAP and carboplatin-taxol regimens as first-line treatment of advanced ovarian cancer (AOC) yield similar survival. We explored the impact of increased dose of cyclophosphamide in a modified CAP regimen on the disease-free survival (DFS) and overall survival (OS) of AOC patients. From February 1994 to June 1997, 164 patients were randomised to receive six cycles every 3 weeks of either standard CEP (S) combining cyclophosphamide (C), 500 mg m(-2), epirubicin (E) 50 mg m(-2), and cisplatin (P) 75 mg m(-2) or intensive CEP (I) with E and P at the same doses, but with (C) 1800 mg m(-2) and filgrastim 5 mug kg(-1) per day x 10 days. Response was evaluated at second-look surgery. Patient characteristics were well balanced. Except for grade 3-4 neutropaenia (S: 54%, I: 38% of cycles), Arm1 presented a significantly more important toxicity: infection requiring antibiotics, grade 3-4 thrombocytopaenia, anaemia, nausea-vomiting, diarrhoea, mucositis. Median follow-up was 84 months. DFS (15.9 vs 14.8 months) and OS (33 vs 30 months) were not significantly different between S and I (P>0.05). Increasing cyclophosphamide dose by more than 3 times with filgrastim support in the modified CAP regimen CEP induces more toxicity but not better efficacy in AOC.