Clinical data and pharmacokinetics of a docetaxel-vinorelbine combination in anthracycline resistant/ relapsed metastatic breast cancer

• Published in: Acta oncologica Vol. 42; no. 3; p. 186
• Main Authors: Airoldi, Mario, Cattel, Luigi, Pedani, Fulvia, Marchionatti, Sara, Tagini, Valentina, Bumma, Cesare, Recalenda, Valeria
• Format: Journal Article
• Language: English
• Published: England 2003
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Disease Progression; Docetaxel; Drug Interactions; Drug Resistance, Neoplasm; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Middle Aged; Neoplasm Metastasis; Neutropenia - chemically induced; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Paclitaxel - analogs & derivatives; Taxoids; Treatment Outcome; Vinblastine - administration & dosage; Vinblastine - adverse effects; Vinblastine - analogs & derivatives; Vinorelbine
• ISSN: 0284-186X
• DOI: 10.1080/02841860310010709

The aim of this study was to evaluate the pharmacokinetic parameters, efficacy and toxicity of a docetaxel and vinorelbine combination in metastatic breast cancer patients previously treated with anthracycline. A population of 40 patients was analyzed; 30 patients (75%) had visceral metastases as the dominant site of disease, including 20 patients (50%) with liver metastases. Three or more organs were involved in 43% of patients. All patients had received prior anthracycline therapy. Five patients (12%) had primary resistant disease, 10 patients (25%) secondary resistant disease and 25 patients (63%) had progressive metastatic breast cancer after first-line chemotherapy. Docetaxel and vinorelbine were given at 80 mg/m2 and 20 mg/m2 i.v., respectively, on day 1 every 3 weeks. After a median of 5 cycles, it was found that 5 patients had a complete remission (13%), 19 a partial remission (48%), 9 had stable disease (22%) and 7 had progressive disease (17%). Response rates in patients with visceral and liver metastases were 57% and 50%, respectively. After a median follow-up of 24 months (13-36), median time to progression was 8.5 months and median overall survival 17 months. Grade 4 neutropenia was observed in 78% of courses (febrile neutropenia in 9%). Possible pharmacokinetic interactions were studied in 23 patients by administering docetaxel immediately followed by vinorelbine (protocol A) or vinorelbine followed by docetaxel (protocol B). Patients in protocol B had significantly higher vinorelbine plasma levels and more pronounced neutropenia. Docetaxel plus vinorelbine is an effective combination in anthracycline resistant/relapsed metastatic breast cancer. The administration sequence docetaxel --> vinorelbine is safer than the reverse order.