Phase II study of pemetrexed-gemcitabine combination in patients with advanced-stage non-small cell lung cancer.
OBJECTIVE
Cisplatin is one of the most active agents for the treatment of non-small cell lung cancer (NSCLC). It is also known for significant toxicity, which makes it unsuitable for certain patients. Our purpose was to evaluate the efficacy and toxicity of a promising cisplatin-free combination, gemcitabine plus pemetrexed, in NSCLC.


METHODS
Chemo-naive patients with inoperable NSCLC were eligible for this study. Gemcitabine (1250 mg/m2) was given intravenously on days 1 and 8, followed by intravenous pemetrexed (500 mg/m2) on day 8. After inclusion of 13 patients, folic acid and vitamin B12 supplementation was added to lower pemetrexed-induced toxicity. Quality of life was assessed with the Lung Cancer Symptom Scale.


RESULTS
Sixty patients enrolled; 58 were evaluable for response. All patients had a World Health Organization performance status of 0 or 1. Eighty-seven percent had stage IV disease. Nine patients had a confirmed partial response [overall response rate, 15.5%; 95% confidence interval (CI), 7.3-27.4%]. Twenty-nine (50.0%) patients had stable disease. Median overall survival was 10.1 months (95% CI, 7.9-13.0 months), with a 1- and 2-year overall survival of 42.6% (95% CI, 30.0-55.3%) and 18.5% (95% CI, 7.9-29.1%). Median progression-free survival was 5.0 months. Median response duration was 3.3 months. There were no deaths attributed to treatment. Common Toxicity Criteria grade 3/4 toxicities were neutropenia (61.7%), febrile neutropenia (16.7%), fatigue (23.3%), and elevations of aspartate aminotransferase (15.0%) and alanine aminotransferase (20.0%).


CONCLUSIONS
This combination had good tolerance and achieved promising overall survival with extended 1- and 2-year survival rates. This cisplatin-free regimen warrants further evaluation in randomized trials.
Institut Gustave Roussy, Villejuif, France.
Christian
C
Monnerat
Thierry
T
Le Chevalier
Karen
K
Kelly
Coleman K
CK
Obasaju
Julie
J
Brahmer
Silvia
S
Novello
Takashi
T
Nakamura
Astra M
AM
Liepa
Laurence
L
Bozec
Paul A
PA
Bunn
David S
DS
Ettinger
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D019587:Dietary Supplements; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000633:toxicity; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D016019:Survival Analysis; D013997:Time Factors; D014815:Vitamins; D000093542:Gemcitabine
D005971:Glutamates; D014815:Vitamins; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine