title: Phase I trial of gemcitabine, doxorubicin and cisplatin (GAP) in patients with advanced solid tumors.
abstract: 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.
authors.affiliation: Princess Margaret Hospital, University Health Network, Department of Medical Oncology and Hematology, Toronto, Ontario, Canada.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Duran
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
authors.forename: Eric X
authors.initials: EX
authors.lastname: Chen
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sturgeon
authors.forename: Soo F
authors.initials: SF
authors.lastname: Chin
authors.forename: Shirley
authors.initials: S
authors.lastname: Brown
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.forename: Michelle
authors.initials: M
authors.lastname: Nottage
mesh_terms: 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
chemical_list: D003841:Deoxycytidine; D004317:Doxorubicin; D002945:Cisplatin; D000093542:Gemcitabine