title: Phase I clinical and pharmacokinetic study of sorafenib in combination with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
abstract: OBJECTIVE
  Unsatisfactory efficacy of current treatments for advanced lung cancer has prompted the search for new therapies, with sorafenib, a multikinase inhibitor, being one candidate drug. This phase I trial was conducted to evaluate drug safety and pharmacokinetics as well as tumor response of sorafenib in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Eligible patients received paclitaxel (200 mg/m(2)) and carboplatin (area under the curve [AUC]of 6 mg min mL(-1)) on day 1 and sorafenib (400 mg, twice daily) on days 2 through 19 of a 21-day cycle.
  
  
  RESULTS
  Four of the initial six patients (cohort 1) experienced dose-limiting toxicities (DLTs), resulting in amendment of the treatment protocol. An additional seven patients (cohort 2) were enrolled, two of whom developed DLTs. DLTs included erythema multiforme, hand-foot skin reaction, and elevated plasma alanine aminotransferase in cohort 1 as well as gastrointestinal perforation at a site of metastasis and pneumonia in cohort 2. Most adverse events were manageable. One complete and six partial responses were observed among the 12 evaluable patients. Coadministration of the three drugs had no impact on their respective pharmacokinetics.
  
  
  CONCLUSIONS
  The present study confirmed that sorafenib at 400 mg once daily in combination with carboplatin AUC 5 mg min mL(-1) and paclitaxel 200 mg/m(2) is feasible in Japanese patients with advanced NSCLC. The results of this study also showed that this combination therapy had encouraging antitumor activity and was not associated with relevant pharmacokinetic interaction in Japanese NSCLC patients.
authors.affiliation: Department of Medical Oncology, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8511, Japan. chi-okamoto@dotd.med.kindai.ac.jp
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Morinaga
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kaneda
authors.forename: Shinya
authors.initials: S
authors.lastname: Ueda
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.forename: Akira
authors.initials: A
authors.lastname: Kawada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukino
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tanigawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D003710:Demography; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011859:Radiography; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D016190:Carboplatin; D017239:Paclitaxel