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

✍ Scribed by 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

• Book ID: 102109240
• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 262 KB
• Volume: 104
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/cncr.21188

✦ Synopsis

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/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. Cancer 2005. © 2005 American Cancer Society.