[Oral vinorelbine: pharmacology and treatment outcome in non-small cell bronchial carcinoma and breast carcinoma].
The development of an oral formulation of vinorelbine (Navelbine softgelatine capsules, Pierre Fabre Pharma, Freiburg i.Br., Germany) represents a significant advance in the treatment of patients with cancer. Oral chemotherapy is more convenient for the patients and brings significant time savings. Vinorelbine is rapidly absorbed after oral ingestion. The bioavailability is in the range of 33 to 43% and is not affected by concomitant food intake or by vomiting occuring 1.5 h or later after dosing. No significant differences in the pharmacokinetics of oral vinorelbine were observed between elderly (> or =70 years) and younger patients. The recommended dose schedule for oral vinorelbine is 60 mg/m(2) weekly for the initial 3 weeks (cycle 1) and 80 mg/m(2) weekly thereafter. However, if severe neutropenia is encountered during the first cycle, treatment is continued with weekly doses of 60 mg/m(2). Bioavailability studies have demonstrated that oral vinorelbine doses of 60 and 80 mg/m(2) are comparable to intravenous doses of 25 and 30 mg/m(2), respectively. Several clinical studies have demonstrated that the new oral formulation of vinorelbine can be safely administered, even to elderly patients, and is comparable in activity to intravenous vinorelbine in advanced non-small cell lung cancer (NSCLC) and metastatic breast cancer (MBC). A randomized phase II comparison of oral vinorelbine at the recommended dose schedule vs. intravenous vinorelbine at 30 mg/(2) in patients with advanced NSCLC found no significant differences in response rate, progression-free and overall survival between the two treatments. In studies of combination chemotherapy using vinorelbine plus cisplatin or carboplatin in advanced NSCLC, or vinorelbine plus taxanes, capecitabine,epirubicin, or the monoclonal HER2/neu antibody trastuzumab in MBC, intravenous vinorelbine could be completely or partially replaced by oral vinorelbine, resulting in maintained efficacy, good tolerability and improved patient convenience. Concurrent chemoradiation with oral vinorelbine and cisplatin was shown to be well tolerated and produced significant down-staging in patients with locally advanced NSCLC. Metronomic chemotherapy is a new treatment approach designed to maximize the antiangiogenic effect. Oral vinorelbine given every other day at low doses is currently evaluated in patients with refractory solid tumors. Oral vinorelbine has also proven useful as a substitute for intravenous vinorelbine in patients experiencing intractable acute tumor pain during or after intravenous infusion of vinorelbine.
vbmed@t-online.de
Volker
V
Bartsch
D000284:Administration, Oral; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine