Pemetrexed and gemcitabine for biliary tract and gallbladder carcinomas: a North Central Cancer Treatment Group (NCCTG) phase I and II Trial, N9943.
OBJECTIVE
To determine the maximum tolerated dose (MTD) and efficacy of pemetrexed and gemcitabine in patients with either biliary tract or gallbladder carcinoma.


METHODS
Patients with unresectable previously untreated biliary tract cancers were eligible for participation. An initial phase I trial was performed to determine the MTD using an every-2-weeks schedule. The MTD was then used in the phase II portion of the trial. The primary end point for the phase II portion was 6-month survival with a planned accrual of 59 patients.


RESULTS
Overall, 63 eligible patients were enrolled. The MTD was established as pemetrexed 500 mg/m2 IV over 10 min and gemcitabine 800 mg/m2 IV at 10 mg/m2 per minute on days 1 and 15 of an every-4-weeks schedule with vitamin B12 and folate supplementation. Fifty-eight patients were included in the phase II portion. Median age was 61 and median follow-up was 18.2 months. A median of three cycles of treatment was given. Six-month survival was 55% and the median survival was 6.6 months (95% confidence interval 5.4-8.7 months) with a median time to progression of 3.8 months (2.4-5.4). Forty-seven (81%) experienced at least one grade 3+ adverse event, and 28 patients (48%) experienced at least one grade 4 adverse event, most of which were due to grade 4 neutropenia.


CONCLUSIONS
The addition of pemetrexed to fixed-dose-rate gemcitabine, in a biweekly schedule, did not enhance the activity of gemcitabine in patients with biliary tract or gallbladder carcinoma.
Alberts
Steven R
SR
Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA. Alberts.steven@mayo.edu
Sande
Jonathan R
JR
Foster
Nathan R
NR
Quevedo
Fernando J
FJ
McWilliams
Robert R
RR
Kugler
John W
JW
Fitch
Tom R
TR
Jaslowski
Anthony J
AJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine