Phase II study of pemetrexed disodium (Alimta) administered with oral folic acid in patients with advanced gastric cancer.
BACKGROUND
The aim of this study was to assess the activity of pemetrexed in patients with advanced gastric cancer.


METHODS
Thirty-eight eligible patients (median age 60 years) received pemetrexed 500 mg/m(2) every 3 weeks. Since toxicity was considerable in the first six patients, the protocol was amended to supplement subsequent patients with oral folic acid (5 mg/day on days -2 to +2 of every cycle).


RESULTS
Among 36 stage IV patients evaluable for efficacy (six non-supplemented\30 supplemented), there were two complete and six partial responses. The response rate was 21% (95% confidence interval 8% to 32%) according to intention-to-treat analysis. All responding patients were in the supplemented group. The median duration of response was 4.6 months and the median survival was 7.8 months. Five of six non-supplemented patients (83%) developed grade 3/4 neutropenia; two (33%) unsupplemented patients discontinued; two (33%) patients died due to toxicity. In the supplemented group, 12 of 32 patients (37%) had grade 3/4 neutropenia. None of the supplemented patients discontinued treatment due to hematological toxicity. Severe non-hematological toxicities were infrequent.


CONCLUSIONS
The activity of pemetrexed is promising in light of the tumor burden in these patients (all patients were stage IV and 39% had three or more organs involved). Toxicities were remarkably decreased with folic acid supplementation. Combination studies are warranted.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006397:Hematinics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D000068437:Pemetrexed; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D005971:Glutamates; D006397:Hematinics; D000068437:Pemetrexed; D006147:Guanine; D005492:Folic Acid