Pemetrexed and gemcitabine for biliary tract and gallbladder carcinomas: a North Central Cancer Treatment Group (NCCTG) phase I and II Trial, N9943.

Abstract

PURPOSE:

To determine the maximum tolerated dose (MTD) and efficacy of pemetrexed and gemcitabine in patients with either biliary tract or gallbladder carcinoma.

PATIENTS AND 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.

CONCLUSION:

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.

• Authors: Steven R Alberts, Jonathan R Sande, Nathan R Foster, Fernando J Quevedo, Robert R McWilliams, John W Kugler, Tom R Fitch, Anthony J Jaslowski
• Journal: Journal of gastrointestinal cancer (J Gastrointest Cancer) Vol. 38 Issue 2-4 Pg. 87-94 ( 2007) ISSN: 1941-6628 [Print] United States
• PMID: 19023677 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Glutamates
• Pemetrexed
• Deoxycytidine
• Guanine
• Gemcitabine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biliary Tract Neoplasms (drug therapy, pathology)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Female
• Gallbladder Neoplasms (drug therapy, pathology)
• Glutamates (administration & dosage)
• Guanine (administration & dosage, analogs & derivatives)
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Staging
• Pemetrexed
• Prognosis
• Survival Rate
• Treatment Outcome
• Gemcitabine