A phase I study of combination of intravenous gemcitabine, oxaliplatin, and 5-FU with daily oral thalidomide (GOFT) in metastatic/locally advanced pancreatic carcinoma patients.

Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. ysshan@mail.ncku.edu.tw

BACKGROUND/AIMS: The phase I study was to determine the maximum tolerance dose and dose-limiting toxicity of gemcitabine/oxaliplatin/5-FU/thalidomide (GOFT) in patients with advanced pancreatic cancer. METHODOLOGY: Chemotherapy-naive patients with histologically proven locally advanced or metastatic pancreatic cancer were enrolled. Gemcitabine was given in a 1-hour infusion followed by oxaliplatin in a 2-hour infusion on day 1, and 5-FU in a 24-hour infusion on day 2, and oral thalidomide 100mg was given daily after intravenous chemotherapy. This regimen was given every 2 weeks. Dose levels of regimen were: level I: gemcitabine 1000mg/m2 + oxaliplatin 60mg/ m2 + 5-FU 1000mg/m2 + thalidomide 100mg/day, level II: gemcitabine 1000mg/m2 + oxaliplatin 70mg/m2 + 5-FU 1000mg/m2 + thalidomide 100mg/day, level III: gemcitabine 1250mg/m2 + oxaliplatin 60mg/m2 + 5-FU 1000mg/m2 + thalidomide 100mg/day. The NCI-CTC grade 3/4 toxicity was used for dose-limiting toxicity. Maximum tolerance dose was determined after the first two cycles in each patient. RESULTS: There were 6 patients in level I, 6 patients in level II, and 1 patient in level III. One of the 6 patients had DLT in level I (grade 3 infection and vomiting), 2 of 6 patients had DLT in level II (grade 3 leukopenia) and 1 patient in level III had DLT (grade 3 leukopenia and stomatitis). Other toxicities at level I/II were grade 1/2 leukopenia (7 episodes), grade 1/2 anemia (5), grade 1/2 nausea (5), grade 1 diarrhea (2), grade 1 alopecia (2), grade 1 skin (2), grade 1 allergy (1). CONCLUSIONS: The GOFT regimen was well tolerated and showed good treatment effect on the pancreatic cancer. We recommended the dose of level II GOFT regimen for further phase II trial.

PMID: 18251177 [PubMed - indexed for MEDLINE]