title: Phase I trial of carboplatin and paclitaxel with escalating doses of oral topotecan in patients with solid tumors.
abstract: Carboplatin, paclitaxel, and topotecan have activity against a variety of cancers. This phase I study was designed to determine the maximum tolerated dose of oral topotecan when given in combination with carboplatin and paclitaxel. Eligibility criteria were as follows: Karnofsky Performance score greater than or equal to 80; and adequate hepatic, renal, and bone marrow function. Patients received paclitaxel 175 mg/m2 intravenously followed by carboplatin AUC 5 iv on day 1 every 3 weeks for up to 6 cycles. Cohorts of 3 to 5 were treated with escalating doses of oral topotecan on days 1 to 5, initially at 0.75 mg/m2 then 1 mg/m2 and 1.25 mg/m2 in subsequent cohorts. Thirteen patients were treated. Three of three patients in cohort 1 had grade IV neutropenia, with one neutropenic fever and one patient requiring a platelet transfusion. In cohort 2, three of five patients had grade III/IV neutropenia including two with neutropenic fever. Four patients required blood transfusions and one required platelet transfusions. In cohort 3, three of five had grade III/IV neutropenia, one of five had grade IV thrombocytopenia, and one patient required blood transfusions. In conclusion, this three-drug regimen resulted in significant cumulative myelosuppression in the doses and schedule tested in this phase I trial. Subsequent combinations of these drugs should focus on alternate doses or schedules.
authors.affiliation: Indiana University, Indianapolis, Indiana, U.S.A.
authors.forename: Nasser
authors.initials: N
authors.lastname: Hanna
authors.forename: Chris
authors.initials: C
authors.lastname: Sweeney
authors.forename: Karen
authors.initials: K
authors.lastname: Fife
authors.forename: Sheila
authors.initials: S
authors.lastname: Dropcho
authors.forename: David E
authors.initials: DE
authors.lastname: Seitz
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage*
chemical_list: D019772:Topotecan; D016190:Carboplatin; D017239:Paclitaxel