Annals of Oncology 14:574-579, 2003
© 2003 European Society for Medical Oncology
Original Paper |
Activity of raltitrexed and gemcitabine in advanced pancreatic cancer
1 Institute of Medical Oncology, 2 Department of Visceral and Transplantation Surgery, University of Bern, Bern, Switzerland
Received 23 July 2002; revised 9 September 2002; accepted 20 September 2002
Background:
Gemcitabine has evolved as standard therapy in advanced pancreatic cancer since the demonstration of a significant clinical benefit. Phase II trials have shown that gemcitabine can be successfully combined with thymidylate synthase (TS) inhibitors such as continuous-infusion 5-fluorouracil (5-FU). However, continuous-infusion 5-FU is inconvenient because of the need for a central venous access. The aim of this study was to assess the efficacy and safety of gemcitabine in combination with raltitrexed (Tomudex), a novel and selective TS inhibitor that has the advantage of a 3-weekly treatment interval and manageable toxicity.
Patients and methods:
Chemotherapy-naïve patients with measurable advanced pancreatic cancer were treated with raltitrexed 3 mg/m2 as a 15-min infusion on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8, every 21 days.
Results:
Twenty-five eligible patients (17 male, eight female) with metastatic (21 patients) or locally advanced (four patients) disease entered the study. The median number of courses per patient was four (range 1–14). One patient was not evaluable for response. There were three partial remissions [12%; 95% confidence interval (CI) 2.6% to 31.2%] and nine stable disease situations (36%; 95% CI 18.0% to 57.5%), while the tumours of 12 patients (48%; 95% CI 27.8% to 68.7%) showed progressive disease after three treatment cycles. WHO grade 3/4 toxicity was rare and symptomatic in only one patient, who experienced grade 4 diarrhoea and grade 3 nausea and vomiting. Symptomatic benefit was seen in 12 patients. Median survival was 185 days (95% CI 129–241) with six patients still alive.
Conclusions:
The efficacy of raltitrexed plus gemcitabine is limited, but compares well with other chemotherapy treatment options in advanced pancreatic cancer. However, this combination is convenient and symptomatic toxicity is rare. Thus, raltitrexed and gemcitabine should be investigated further in combination with drugs interfering with specific molecular targets.
Key words: gemcitabine, pancreatic cancer, phase II, raltitrexed