title: Phase I/II study of paclitaxel and vinorelbine in metastatic breast cancer.
abstract: Paclitaxel and vinorelbine are among the most active new agents in metastatic breast cancer. Both in vitro and in vivo studies have shown that the combined administration of these two microtubule-targeting agents is feasible and worthwhile. Based on the promising preclinical data, patients with metastatic breast cancer no longer amenable to conventional treatment were entered into a phase I/II study in which the vinorelbine dose was fixed at 30 mg/sqm and paclitaxel was started at 90 mg/sqm and then subsequently escalated by 30 mg/sqm per step. Cycles were repeated every 21 days. Hematopoietic growth factor support was provided from the 4th dose level onwards. Grade III neutropenia was observed only in 2 patients treated at the 5th dose level. Thrombocytopenia never reached grade 3. Neurotoxicity was considered dose-limiting, since grade 3 peripheral neuropathy occurred in all three patients treated at the 6th dose level. Other toxicities were mild. Paclitaxel 210 mg/sqm and vinorelbine 30 mg/sqm was the selected combination for phase II. Overall response rate in 34 evaluable patients was 38% (95% confidence interval (C.I.), 22% to 54%). In particular, 3 complete responses (9%) and 10 partial responses (29%) were observed. The observed level of antitumor activity, with an overall response rate of 38% and a median duration of response of 12 months, is of interest, since the study was targeted only to anthracycline-pretreated patients, most of whom had adverse prognostic features. The evaluation of a combination of vinorelbine and paclitaxel as first-line therapy in metastatic breast cancer seems worthwhile and is currently undergoing.
authors.affiliation: Istituto di Medicina Interna, Università di Cagliari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tortoriello
authors.forename: G
authors.initials: G
authors.lastname: Facchini
authors.forename: F
authors.initials: F
authors.lastname: Caponigro
authors.forename: M
authors.initials: M
authors.lastname: Santangelo
authors.forename: G
authors.initials: G
authors.lastname: Benassai
authors.forename: G
authors.initials: G
authors.lastname: Persico
authors.forename: A
authors.initials: A
authors.lastname: Citarella
authors.forename: M
authors.initials: M
authors.lastname: Carola
authors.forename: N
authors.initials: N
authors.lastname: Marzano
authors.forename: R V
authors.initials: RV
authors.lastname: Iaffaioli
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D017239:Paclitaxel; D000077235:Vinorelbine