title: Gefitinib (IRESSA) with vinorelbine or vinorelbine/cisplatin for chemotherapy-naive non-small cell lung cancer patients.
abstract: This phase I study assessed the safety, pharmacokinetics, and efficacy of gefitinib (IRESSA) combined with vinorelbine or vinorelbine/cisplatin in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). Patients received gefitinib 250 mg/day and vinorelbine (group A; n = 6) or vinorelbine/cisplatin (group B; n = 8). An additional set of group B patients (n = 9) received gefitinib 500 mg/day with vinorelbine/cisplatin. Adverse events were consistent with individual treatments of gefitinib (mild reversible rash, diarrhea) and chemotherapy (asthenia, fever, nausea, vomiting, constipation), although there was a higher than expected incidence of Common Toxicity Criteria grade 3 or 4 hematologic adverse events, specifically febrile neutropenia and neutropenia. Pharmacokinetic data suggested that neither of the chemotherapy regimens affected steady-state exposure to gefitinib and also that steady-state gefitinib did not alter exposure to vinorelbine or cisplatin. Objective, durable antitumor activity was observed: five partial responses (one in group A; four in group B) and six patients with stable disease (all in group B). The safety data demonstrated that gefitinib with vinorelbine or vinorelbine/cisplatin resulted in severe myelosuppression leading to an unacceptable rate of febrile neutropenia. This study does not support the concurrent administration of gefitinib and vinorelbine, with or without cisplatin, as a valid treatment for advanced NSCLC.
authors.affiliation: Montpellier Academic Hospital, Montpellier, France. pujol@cyber-sante.org
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pujol
authors.forename: Patrick
authors.initials: P
authors.lastname: Viens
authors.forename: Paul
authors.initials: P
authors.lastname: Rebattu
authors.forename: Scott A
authors.initials: SA
authors.lastname: Laurie
authors.forename: Ronald
authors.initials: R
authors.lastname: Feld
authors.forename: Anne
authors.initials: A
authors.lastname: Deneulin
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Fandi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000077235:Vinorelbine
chemical_list: D011799:Quinazolines; D014747:Vinblastine; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D002945:Cisplatin; D000077235:Vinorelbine; D000077156:Gefitinib