TY - JOUR
T1 - Phase II study of the farnesyltransferase inhibitor lonafarnib with paclitaxel in patients with taxane-refractory/resistant nonsmall cell lung carcinoma
AU - Kim, Edward S.
AU - Kies, Merrill S.
AU - Fossella, Frank V.
AU - Glisson, Bonnie S.
AU - Zaknoen, Sara
AU - Statkevich, Paul
AU - Munden, Reginald F.
AU - Summey, Carmen
AU - Pisters, Katherine M W
AU - Papadimitrakopoulou, Vali
AU - Tighiouart, Mourad
AU - Rogatko, Andre
AU - Khuri, Fadlo R.
PY - 2005/8/1
Y1 - 2005/8/1
N2 - 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.
AB - 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.
KW - Farnesyltransferase inhibitor
KW - Lonafarnib
KW - Paclitaxel
KW - Taxane-refractory/ resistant nonsmall cell lung carcinoma
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U2 - 10.1002/cncr.21188
DO - 10.1002/cncr.21188
M3 - Article
C2 - 16028213
AN - SCOPUS:22544467757
VL - 104
SP - 561
EP - 569
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 3
ER -