Survival without common toxicity criteria grade 3/4 toxicity for pemetrexed compared with docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC): a risk-benefit analysis.
BACKGROUND
In a recent large phase III study, previously treated patients with advanced non-small cell lung cancer who received pemetrexed demonstrated a survival time similar to patients who received docetaxel (median, 8.3 months with pemetrexed versus 7.9 months with docetaxel), with a more favorable toxicity profile, and significantly fewer Common Toxicity Criteria grade 3/4 toxicities. This is a retrospective risk-benefit analysis of survival without grade 3/4 toxicity, defined as the time to the first occurrence of Common Toxicity Criteria grade 3 or 4 toxicity or death, in the prospective phase III study comparing pemetrexed with docetaxel.


METHODS
A total of 541 patients (of 571 randomized) received either pemetrexed (500 mg/m intravenously [IV]) supplemented with vitamin B12 injections and oral folic acid or docetaxel (75 mg/m IV) on day 1 of 21-day cycles. Survival without grade 3/4 toxicity was analyzed using Kaplan-Meier and Cox methods.


RESULTS
Pemetrexed demonstrated a statistically significantly longer survival without grade 3/4 toxicity compared with docetaxel (hazard ratio = 0.60, 95% confidence interval: 0.50-0.72; p < 0.0001). A supportive analysis based on selected grade 3/4 toxicities (neutropenia lasting >5 days, febrile neutropenia, infection with neutropenia, anemia, thrombocytopenia, fatigue, nausea, vomiting, diarrhea, stomatitis, and neurosensory events) also demonstrated an advantage for pemetrexed (hazard ratio = 0.53; 95% confidence interval: 0.44-0.64; p < 0.0001).


CONCLUSIONS
This analysis of survival without grade 3/4 toxicity suggests a benefit-to-risk profile that favors pemetrexed over docetaxel in the second-line treatment of patients with non-small cell lung cancer.
Pujol
Jean-Louis
JL
Institut Universitaire de Recherche Clinique, Montpellier, Cedex, France. jl-pujol@chu-montpellier.fr
Paul
Sofia
S
Chouaki
Nadia
N
Peterson
Patrick
P
Moore
Patti
P
Berry
Donald A
DA
Salzberg
Marc
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077143:Docetaxel; D005260:Female; D005971:Glutamates / Q000009:adverse effects* / Q000627:therapeutic use; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012189:Retrospective Studies; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D000077143:Docetaxel; D006147:Guanine