title: Oral versus intravenous vinorelbine: clinical safety profile.
abstract: The availability of chemotherapeutic drugs administrable by oral route represents a step forward in the management of cancer patients. Among oral agents, vinorelbine is particularly interesting for its pharmacological characteristics and clinical efficacy. Oral vinorelbine is rapidly absorbed (1.5-3 hours) with an elimination half-life of approximately 40 hours. It shows a low level of binding to plasma proteins (13%), is highly bound to platelets (78%) and has a hepatic metabolism and an absolute bioavailability of 40% with a moderate and similar interpatient variability for the two forms. Food has no influence on the pharmacokinetic profile of oral vinorelbine even if nausea/vomiting is less frequent and less severe in the fed patients than in the fasting patients. Therefore, to ensure patient comfort, it is recommended that oral vinorelbine is administered with a snack. All the metabolites of oral vinorelbine have been identified and, among these, only deacetyl-vinorelbine presented activity demonstrating that for both oral and intravenous (i.v.) routes of administration the drug has the same metabolism pattern. Oral vinorelbine is eliminated mainly in a unconjugated form via the bile. In this process, the CYP 3A4 isoform of cytochrome P450 is mostly involved. Absorption of oral vinorelbine is not delayed in elderly patients. After oral administration, blood concentrations of vinorelbine in elderly patients are within the range of values observed in younger patients. The absolute bioavailability is close to 38% in elderly whereas it is close to 40% in younger patients. This difference is not significant. As compared to the intravenous drug, oral vinorelbine demonstrated linear pharmacokinetics as well an absolute bioavailability of approximately 40%, and a reliable dose-correspondence of 80 mg/m2 oral form --> 30 mg/m2 i.v. and 60 mg/m2 oral --> 25 mg/m2 i.v. Therefore, i.v. and oral forms show similar interindividual variability, same metabolism pattern, reproducible intra-patient blood exposure, and same pharmacokinetic-pharmacodynamic relationship. Oral vinorelbine has shown significant activity in advanced non-small cell lung cancer. Given at 60 mg/m2/week for the first 3 administrations and then increased to 80 mg/m2/week achieved the same efficacy as i.v. vinorelbine in terms of progression-free survival, overall survival, objective response. Mild-to-moderate gastrointestinal toxicity, easily manageable with standard treatment was recorded. Reproducible efficacy compared to previously reported results with vinorelbine i.v. Also, in advanced breast cancer, oral vinorelbine has shown significant activity with a good therapeutic index. Albeit no formal comparison between the oral and the intravenous formulations of vinorelbine has been made, however, the oral route seems to offer major advantages to patients who are faced with a clear decrease in the frequency of hospital admissions as compared to that needed to give intravenous chemotherapy.
authors.affiliation: Department of Experimental Oncology and Clinical Applications, University of Palermo, Palermo, Italy. vittorio.gebbia@tin.it
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gebbia
authors.forename: Christian
authors.initials: C
authors.lastname: Puozzo
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004435:Eating; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008099:Liver / Q000201:enzymology; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D003577:Cytochrome P-450 Enzyme System; D000077235:Vinorelbine