Phase II study of fixed dose rate gemcitabine in patients with pretreated advanced colorectal cancer

Abstract

13558 Background: There is preclinical evidence that gemcitabine has activity in colon cancer. However, previous clinical studies have not clearly demonstrated activity of gemcitabine given as a 30 minute infusion. Prolonged exposure of colon cancer cell lines to gemcitabine appears to have greater antitumour effect compared to shorter exposure (Kornmann et al, Eur J Surg Oncol 2000). Methods: Patients with progressive, pretreated metastatic colorectal cancer received gemcitabine 1500 mg/m2 at a fixed dose rate of 10 mg/m2/min (150 minutes) D1, 8, 15 every 28 days. The primary endpoint was disease control rate (CR/PR/SD) assessed by CT scan. Using a 2-stage statistical design, a total of 37 patients were required to demonstrate at least a 25% disease control rate with 90% power and a 1-sided alpha of 0.05. The 1st accrual stage required at least 6/17 pts to obtain disease control, prior to proceeding to the 2nd stage. Results: 16 patients with a median age of 63 years were treated. The median number of prior lines of chemotherapy was 3 (range: 1–5). The median number of administered gemcitabine doses was 5.5 (range: 1–14). 3 patients achieved SD after 3 cycles, but subsequently progressed. 13 patients either progressed prior to the first scheduled CT scan or had declining performance status requiring removal from the study. 1 patient experienced transient reduction in serum CEA of > 50%. Median progression-free survival was 77 days (95% CI 61–93). Grade 3/4 neutropenia occurred in 4/1 pts; grade 3/4 thrombocytopenia in 6/0 pts. 2 pts had grade 3 infection. As only 3/16 pts achieved disease control, it was not possible to proceed to the 2nd stage and the study was closed to accrual. Conclusions: Gemcitabine administered by fixed dose rate infusion has minimal activity in heavily pretreated patients with advanced colorectal cancer. Gemcitabine monotherapy is not recommended in this patient population. No significant financial relationships to disclose.