Phase II study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in patients with taxane-refractory/resistant nonsmall cell lung carcinoma

Edward S. Kim, Merrill S. Kies, Frank V. Fossella, Bonnie S. Glisson, Sara Zaknoen, Paul Statkevich, Reginald F. Munden, Carmen Summey, Katherine M W Pisters, Vali Papadimitrakopoulou, Mourad Tighiouart, Andre Rogatko, Fadlo R. Khuri

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

BACKGROUND. The authors evaluated the safety, tolerability, and efficacy of treatment using lonafarnib, a novel farnesyltransferase inhibitor (FTI), in combination with paclitaxel in patients with metastatic (Stage IIIB/V), taxane-refractory/resistant nonsmall cell lung carcinoma (NSCLC). METHODS. Patients with NSCLC who experienced disease progression while receiving previous taxane therapy or who had disease recurrence within 3 months after taxane therapy cessation were treated with continuous lonafarnib 100 mg orally twice per day beginning on Day 1 and paclitaxel 175 mg/m2 intravenously over 3 hours on Day 8 of each 21-day cycle. RESULTS. A total of 33 patients were enrolled, 29 of whom were evaluable for response. Partial responses (PR) and stable disease (SD) were observed in 3 (10%) and 11 patients (38%), respectively. Thus, 48% (14 of 29) experienced clinical benefit (PR or SD). The updated and final median overall survival time was 39 weeks and the median disease progression-free survival time was 16 weeks. The combination of lonafarnib and paclitaxel was well tolerated with minimal toxicity. Grade 3 toxicities included fatigue (9%), diarrhea (6%), and dyspnea (6%). Grade 3 neutropenia occurred in only 1 patient (3%). Grade 4 adverse events included respiratory insufficiency in 2 patients (6%) and acute respiratory failure in 1 patient (3%). CONCLUSIONS. Lonafarnib plus paclitaxel demonstrated clinical activity in patients with taxane-refractory/resistant metastatic NSCLC. In addition, the combination of lonafarnib and paclitaxel was well tolerated with minimal toxicity. Evaluation of this combination therapy in additional clinical trials is warranted.

Original languageEnglish (US)
Pages (from-to)561-569
Number of pages9
JournalCancer
Volume104
Issue number3
DOIs
StatePublished - Aug 1 2005

Keywords

  • Farnesyltransferase inhibitor
  • Lonafarnib
  • Paclitaxel
  • Taxane-refractory/ resistant nonsmall cell lung carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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