Most patients with adenocarcinoma of the pancreas present with advanced disease and nearly all will develop local recurrence, metastases or both. Median survival time with standard chemotherapy is less than 6 months. Docetaxel, gemcitabine and cisplatin have each shown activity in pancreatic cancer as single agents.OBJECTIVES
To determine the efficacy and toxicity of docetaxel plus gemcitabine or docetaxel plus cisplatin for advanced pancreatic carcinoma, to assist selection of the optimal regimen for further evaluation in comparison with a standard treatment in a phase III trial.DESIGN AND INTERVENTION
In this open, randomized, phase II trial, patients from five countries (17 institutions) were enrolled between October 1999 and March 2001. Chemotherapy-naive adult patients with metastatic or unresectable locoregionally advanced adenocarcinoma of the pancreas who had adequate baseline bone marrow and renal function and good WHO performance status (<2) were included. Patients were randomly assigned to receive at least six 21-day cycles of chemotherapy by intravenous infusion: either gemcitabine 800 mg/m2 on days 1 and 8 plus docetaxel 85 mg/m2 on day 8; or docetaxel 75 mg/m2 followed by cisplatin 75 mg/m2, both on day 1.OUTCOME MEASURES
The primary outcome measures were tumor response rate graded using the WHO criteria, and severe acute toxicity rate, graded according to the National Cancer Institute Common Toxicity Criteria version 2.0. Secondary endpoints were progression-free survival, overall survival and duration of response.RESULTS
Of the 96 patients enrolled, 89 patients were analyzed for safety and 70 patients for response. Median treatment duration was four cycles (range 1-12) in both groups. Overall response (complete response plus partial response) occurred in seven patients (19.4%; 95% CI 8.2-36%) receiving docetaxel plus gemcitabine and eight patients (23.5%; 95% CI 10.7-41.2%) receiving docetaxel plus cisplatin. In patients receiving docetaxel plus gemcitabine, median progression-free survival was 3.9 months (95% CI 3-4.7 months) and median survival was 7.4 months (95% CI 5.6-11 months) with 1-year survival of 29.8% (95% CI 16.7-42.9%). In patients receiving docetaxel plus cisplatin, the median progression-free survival was 2.8 months (95% CI 2.6-4.6 months), median survival was 7.1 months (95% CI 4.8-8.7 months), with 1-year survival 16.1% (95% CI 5.2-27%). Severe acute toxicity occurred in four patients receiving docetaxel plus gemcitabine (9%) and seven patients receiving docetaxel plus cisplatin (16%). Febrile neutropenia of grade 3 or above occurred in 9% of patients receiving docetaxel plus gemcitabine and 16% of patients receiving docetaxel plus cisplatin.CONCLUSION
Docetaxel plus gemcitabine is active in pancreatic cancer and should be evaluated further in comparative trials. Combination of docetaxel plus cisplatin should be evaluated following gemcitabine pretreatment.