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.
OBJECTIVE
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.


METHODS
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.
Shan
Yan-Shen
YS
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
Lin
Pin-Wen
PW
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D013792:Thalidomide / Q000008:administration & dosage*; D014057:Tomography, X-Ray Computed; D000093542:Gemcitabine
D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D013792:Thalidomide; D005472:Fluorouracil; D000093542:Gemcitabine