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

Cancer. 2005 Aug 1;104(3):561-9. doi: 10.1002/cncr.21188.


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/m(2) 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Bridged-Ring Compounds / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug Therapy, Combination
  • Enzyme Inhibitors / therapeutic use*
  • Farnesyltranstransferase
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging
  • Paclitaxel / therapeutic use*
  • Piperidines / therapeutic use*
  • Pyridines / therapeutic use*
  • Remission Induction
  • Survival Rate
  • Taxoids / therapeutic use
  • Treatment Outcome


  • Antineoplastic Agents, Phytogenic
  • Bridged-Ring Compounds
  • Enzyme Inhibitors
  • Piperidines
  • Pyridines
  • Taxoids
  • taxane
  • Alkyl and Aryl Transferases
  • Farnesyltranstransferase
  • lonafarnib
  • Paclitaxel