SCOTCERV: A phase II trial of docetaxel and gemcitabine as second-line chemotherapy in cervical cancer

Abstract

5548 Background: Concurrent Cisplatin chemotherapy along with radiotherapy is standard therapy for locally advanced cervical cancer. There is no established second line regimen. Taxanes and Gemcitabine are not thought to share drug resistance with Cisplatin. In combination they are reasonably tolerated; myelosuppression is the dose limiting toxicity. Response is more likely in recurrences outside the irradiated area. Methods: This was a multi-centre phase II trial of Docetaxel (75mg/m2 d1) and Gemcitabine (1,000 mg/m2 d1,d8) in relapsed patients (pts) after treatment with cisplatin alone or in combination (excluding with taxanes) and/or radiotherapy. A Gehan two-stage design was used (minimum response rate requirement 25%). Pts had to have disease assessable by RECIST outside the irradiated pelvis and adequate organ function. After 12 pts the Docetaxel dose was reduced to 60 mg/m2. Results: 26 eligible pts were recruited to the study; information is available currently for 24. The median age is 43 years (range 30–62) and the median time from prior treatment is 12 months (1–55). 23 pts had prior chemoradiotherapy. Performance status: 0 (15) or 1 (9). Histology: squamous 17, adenoCa (6) mixed (1). Major metastatic sites were lung (11) and para-aortic nodes (11). The principal toxicity was neutropenia (gd 3 (8), gd 4 (8)) with 4 pts experiencing grade 3 febrile neutropenia. Dose reductions occurred in 29% of pts (Docetaxel) and 25% of pts (Gemcitabine), primarily for neutropenic fever. Haematological toxicity resulted in d8 Gemcitabine being omitted in 41% of cycles. 1 patient had gd3 SOB and 1 patient gd 3 diarrhoea. Reduction of Docetaxel dose did not reduce haematological toxicity. 5 pts have not, as yet, had response reported. In 19 pts (16 completed therapy) there was 1 CR, 4 PR, 6 stable disease, 7 progressions and 1 unevaluable. The overall response rate is 26% (95% ci 9%-51%). Conclusions: This preliminary data shows this combination has activity against platinum resistant metastatic cervical cancer, although the ability to deliver d8 Gemcitabine is compromised. Final results will be available for the meeting. [Table: see text]