Phase I clinical and pharmacokinetic study of sorafenib in combination with carboplatin and paclitaxel in patients with advanced non–small cell lung cancer
Open Access
- 18 September 2009
- journal article
- phase i-studies
- Published by Springer Science and Business Media LLC in Investigational New Drugs
- Vol. 28 (6), 844-853
- https://doi.org/10.1007/s10637-009-9321-x
Abstract
Summary Objectives 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/m2) 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. Conclusion 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/m2 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.Keywords
This publication has 25 references indexed in Scilit:
- Dermatologic symptoms associated with the multikinase inhibitor sorafenibJournal of the American Academy of Dermatology, 2009
- Cancer Statistics, 2008CA: A Cancer Journal for Clinicians, 2008
- Phase I study of sorafenib in Japanese patients with hepatocellular carcinomaCancer Science, 2007
- Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Sorafenib: A Review of Four Phase I Trials in Patients with Advanced Refractory Solid TumorsThe Oncologist, 2007
- Phase I Trial of Sorafenib in Combination with IFN α-2a in Patients with Unresectable and/or Metastatic Renal Cell Carcinoma or Malignant MelanomaClinical Cancer Research, 2007
- Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistanceBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2006
- Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: Is rash associated with treatment outcome?European Journal Of Cancer, 2006
- Phase I Trial of Sorafenib and Gemcitabine in Advanced Solid Tumors with an Expanded Cohort in Advanced Pancreatic CancerClinical Cancer Research, 2006
- Targeting RAS signalling pathways in cancer therapyNature Reviews Cancer, 2003
- New Guidelines to Evaluate the Response to Treatment in Solid TumorsJNCI Journal of the National Cancer Institute, 2000