title: Topotecan and gemcitabine in platinum/paclitaxel-resistant ovarian cancer.
abstract: 24 patients were enrolled into a phase I-II study conducted to determine the maximum tolerated doses of topotecan-gemcitabine in sequential combination and the response rate in platinum/paclitaxel resistant ovarian cancer patients. A total of 83 courses are evaluable, with a median number of three cycles administered per patients (range 2-7). Topotecan was administered on days 1-5 by 30 min i.v. infusion immediately after gemcitabine given by 30 min i.v. on days 1 and 3; cycles were repeated every 28 days. The starting doses were topotecan 0.7 mg/m(2) and gemcitabine 200 mg/m(2). Following dose levels were 08/400; 0.9/600; 0.9/800 for topotecan and gemcitabine, respectively. The maximum tolerated dose (MTD) was reached at dose level 3, the dose-limiting toxicity being represented by febrile neutropenia and thrombocytopenia. After the MTD was reached, granulocyte-colony-stimulating factor was administered in 27% of cycles. Mild and manageable was non hematological toxicity. All patients are so far evaluable for response. Among them 2 complete responses (8.3%; 95% CI: 2.6-19), 1 partial response (4.2%; 95% CI: 3.8-12), 9 no change (37.5%; 95% CI: 18-56.8) and 12 progressions (50%; 95% CI: 30-70) have been registered. Based on these data, there is no evidence that combining topotecan and gemcitabine is better than using either of the two drugs used separately.
authors.affiliation: Department of Obstetrics/Gynaecology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Greggi
authors.forename: M G
authors.initials: MG
authors.lastname: Salerno
authors.forename: G
authors.initials: G
authors.lastname: D'Agostino
authors.forename: G
authors.initials: G
authors.lastname: Ferrandina
authors.forename: D
authors.initials: D
authors.lastname: Lorusso
authors.forename: L
authors.initials: L
authors.lastname: Manzione
authors.forename: S
authors.initials: S
authors.lastname: Mancuso
authors.forename: G
authors.initials: G
authors.lastname: Scambia
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives; D018450:Disease Progression; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D012008:Recurrence; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D003841:Deoxycytidine; D019772:Topotecan; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine