A phase I/II study of combination chemotherapy with gemcitabine and 5-fluorouracil for advanced pancreatic cancer.

Background: In an effort to improve efficacy of single-agent gemcitabine in pancreatic cancer, several studies have examined the effects of 5-FU combined with gemcitabine. However, no studies to date have been performed in Japanese patients. We thus conducted a phase I/II study of gemcitabine and infusional 5-FU in Japanese patients to determine a recommended dosage for this combination and clarify efficacy and toxicity.

Methods: Phase I evaluated the frequency of dose limiting toxicity of two 5-FU dosages (400 and 500 mg/m(2)/day) infused continuously over 5 days combined with gemcitabine 1000 mg/m(2) x 3 every 4 weeks. Results from phase I determined the recommended dosage to be examined in phase II for effect on survival period, clinical benefit response (CBR), tumor response and safety.

Results: A total of 34 chemo-naive patients were entered into the study. All had a Karnofsky performance of > or =50 points and distant metastases. Dose limiting toxicities in phase I determined the recommended 5-FU dosage at 400 mg/m(2)/day. Grade 3-4 hematological toxicities (neutropenia, leukopenia and thrombocytopenia) were the most common severe toxicities. For the 28 patients administered the recommended dosage, 1-year survival rate was 14.3%, median survival time 7.1 months and progression free survival 3.2 months. Seven patients achieved a 25% overall response rate and three showed 27.3% improvement in CBR.

Conclusion: Although a meaningful survival benefit over single-agent gemcitabine was not demonstrated, 5-FU 400 mg/m(2)/day infused continuously over 5 days in combination with gemcitabine 1000 mg/m(2) x 3 every 4 weeks appeared to be a moderately effective palliative treatment with low toxicity in Japanese patients with metastatic pancreatic cancer.