Japanese Journal of Clinical Oncology Advance Access originally published online on July 26, 2006
Japanese Journal of Clinical Oncology 2006 36(9):557-563; doi:10.1093/jjco/hyl067
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© 2006 Foundation for Promotion of Cancer Research
A Phase I/II Study of Combination Chemotherapy with Gemcitabine and 5-Fluorouracil for Advanced Pancreatic Cancer
1 Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, 2 Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital East, Kashiwa, Chiba and 3 Gastroenterology Division, National Kyushu Cancer Center, Fukuoka, Japan
For reprints and all correspondence: Takuji Okusaka, Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. E-mail: tokusaka{at}ncc.go.jp
Received March 16, 2006; accepted May 23, 2006
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/m2/day) infused continuously over 5 days combined with gemcitabine 1000 mg/m2 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 
50 points and distant metastases. Dose limiting toxicities in phase I determined the recommended 5-FU dosage at 400 mg/m2/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/m2/day infused continuously over 5 days in combination with gemcitabine 1000 mg/m2 x 3 every 4 weeks appeared to be a moderately effective palliative treatment with low toxicity in Japanese patients with metastatic pancreatic cancer.
Key Words: pancreatic cancer • phase I/II study • chemotherapy • gemcitabine • 5-FU