title: Phase I study of amifostine as a cytoprotector of the gemcitabine/cisplatin combination in patients with advanced solid malignancies.
abstract: Our objective was to evaluate the role of amifostine as a cytoprotector in patients with solid tumors receiving the myelosuppressive regimen of gemcitabine/cisplatin combination. Patients with advanced solid tumors were randomized to gemcitabine-amifostine-cisplatin (GAP) or gemcitabine-cisplatin (GP) in Cycle 1 (C1) and then were crossed over to the other treatment in Cycle 2 (C2). Amifostine at 740 mg/m2, followed by gemcitabine and cisplatin, were given for 2 consecutive weeks, every 4 weeks. Two GP combinations were studied: G 1000 mg/m2 and P 40 mg/m2 days 1, 8 (high dose), and G 800 mg/m2 and P 30 mg/m2 days 1, 8 (low dose). Forty patients were enrolled. Of the 19 patients treated with high-dose GP, 11 (nine patients GP in C1 and GAP in C2, two patients GAP in C1 and GP in C2) completed 2 cycles of therapy. Of the eight non-evaluable patients, five patients dropped out due to toxicity or refusal after treatment with amifostine in C1. Of the 21 patients treated with low-dose GP, 15 (eight patients GP in C1 and GAP in C2, seven patients GAP in C1 and GP in C2) were likewise evaluable. The incidence of grade 3 or 4 hematologic toxicities was similar for GP and GAP during the first 2 cycles of treatment, and there were no statistically significant differences in mean absolute neutrophil count, hemoglobin level and platelet levels between the cycles in each arm. We conclude that amifostine, at 740 mg/m2, does not lead to less myelosuppression when combined with gemcitabine/cisplatin chemotherapy regimens and may possibly contribute to subjective intolerance.
authors.affiliation: Albert Einstein Comprehensive Cancer Center, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Missak
authors.initials: M
authors.lastname: Haigentz
authors.forename: Mimi
authors.initials: M
authors.lastname: Kim
authors.forename: Joan
authors.initials: J
authors.lastname: Sorich
authors.forename: Janet
authors.initials: J
authors.lastname: Lee
authors.forename: Howard
authors.initials: H
authors.lastname: Hochster
authors.forename: Manuel
authors.initials: M
authors.lastname: Macapinlac
authors.forename: Deepu
authors.initials: D
authors.lastname: Mirchandani
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sewak
authors.forename: Anna
authors.initials: A
authors.lastname: Pavlick
authors.forename: Matthew
authors.initials: M
authors.lastname: Volm
authors.forename: Anne
authors.initials: A
authors.lastname: Hamilton
authors.forename: Franco M
authors.initials: FM
authors.lastname: Muggia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004999:Amifostine / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018592:Cross-Over Studies; D019610:Cytoprotection; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D004999:Amifostine; D002945:Cisplatin; D000093542:Gemcitabine