Phase I trial of gemcitabine, doxorubicin and cisplatin (GAP) in patients with advanced solid tumors.
A phase I study was conducted to determine the recommended phase II dose, safety profile and anti-tumor activity of a combination regimen of gemcitabine, doxorubicin and cisplatin (GAP). Gemcitabine (G) and doxorubicin (A) were administered on days 1 and 8 at increasing doses (starting level 800 and 15 mg/m, respectively). Cisplatin (P) was given at a fixed dose of 50 mg/m2 (day 1). Treatment cycles were repeated every 3 weeks. Nineteen patients received 76 cycles of treatment. A and G were escalated up to 20 and 1000 mg/m2, and finally de-escalated to 15 and 800 mg/m2. The dose-limiting toxicity was neutropenic fever that was observed in 21% of the patients. Non-hematological toxicities included mild/moderate nausea, vomiting, diarrhea and fatigue, observed in 58, 37, 21 and 95% of the patients, respectively. Of 19 patients with evaluable disease, six patients had a partial response yielding an overall response rate of 31.6 % (95% confidence interval 12.6-56.6%) by intention-to-treat. We conclude that GAP is an active and tolerable treatment combination, with minimal visceral organ toxicities.
Duran
Ignacio
I
Princess Margaret Hospital, University Health Network, Department of Medical Oncology and Hematology, Toronto, Ontario, Canada.
Siu
Lillian L
LL
Chen
Eric X
EX
Oza
Amit M
AM
Sturgeon
Jeremy
J
Chin
Soo F
SF
Brown
Shirley
S
Pond
Gregory R
GR
Nottage
Michelle
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage; D016889:Endometrial Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D000093542:Gemcitabine
D003841:Deoxycytidine; D004317:Doxorubicin; D002945:Cisplatin; D000093542:Gemcitabine