TY - JOUR
T1 - Pemetrexed and oxaliplatin for metastatic colorectal cancer
T2 - results of a phase I Mayo Cancer Center Research Consortium trial, MC0248
AU - Alberts, Steven R.
AU - Kim, George P.
AU - Mahoney, Michelle R.
AU - Gornet, Michael K.
AU - Rubin, Joseph
AU - Ames, Matthew
AU - Goetz, Matthew P.
AU - Weinshilboum, Richard M.
AU - Nicol, Steven J.
AU - Goldberg, Richard M.
N1 - Funding Information:
This study was conducted as a trial of the Mayo Cancer Center Research Consortium with financial support from Eli Lilly and Company.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2007/7
Y1 - 2007/7
N2 - Purpose: Pemetrexed, an antifolate involved in purine and pyrimidine formation, is a potential alternative to fluoropyrimidines in the treatment of colorectal cancer. A phase I trial was performed to establish the maximum tolerated dose (MTD) of pemetrexed and oxaliplatin when B12 and folate supplementation is used. Patients and Methods: Patients with metastatic colorectal cancer received folate (> 350 μg) daily and vitamin B 12 (1000 pg) every 9 weeks starting 7 days before chemotherapy. Pemetrexed over 10 minutes and oxaliplatin over 2 hours were given every 3 weeks in escalating dose cohorts. Results: Twenty-two patients were entered on 6 dose levels. The MTD was established at the highest dose level, pemetrexed 900 mg/m2 and oxaliplatin 130 mg/m2. Toxicities related to treatment at the MTD included grade 3 neutropenia and thrombocytopenia. For all dose levels combined, grade 3/4 toxicities included hematologic, neurologic, and gastrointestinal. Nine of 21 evaluable patients responded overall (response rate, 43%). The time to tumor progression was 11.9 months. Conclusion: The MTD was determined to be pemetrexed 900 mg/m2 and oxaliplatin 130 mg/m2 every 21 days when folate and B12 supplementation are used. Because of the observed tolerability and activity of this regimen, further evaluation is warranted.
AB - Purpose: Pemetrexed, an antifolate involved in purine and pyrimidine formation, is a potential alternative to fluoropyrimidines in the treatment of colorectal cancer. A phase I trial was performed to establish the maximum tolerated dose (MTD) of pemetrexed and oxaliplatin when B12 and folate supplementation is used. Patients and Methods: Patients with metastatic colorectal cancer received folate (> 350 μg) daily and vitamin B 12 (1000 pg) every 9 weeks starting 7 days before chemotherapy. Pemetrexed over 10 minutes and oxaliplatin over 2 hours were given every 3 weeks in escalating dose cohorts. Results: Twenty-two patients were entered on 6 dose levels. The MTD was established at the highest dose level, pemetrexed 900 mg/m2 and oxaliplatin 130 mg/m2. Toxicities related to treatment at the MTD included grade 3 neutropenia and thrombocytopenia. For all dose levels combined, grade 3/4 toxicities included hematologic, neurologic, and gastrointestinal. Nine of 21 evaluable patients responded overall (response rate, 43%). The time to tumor progression was 11.9 months. Conclusion: The MTD was determined to be pemetrexed 900 mg/m2 and oxaliplatin 130 mg/m2 every 21 days when folate and B12 supplementation are used. Because of the observed tolerability and activity of this regimen, further evaluation is warranted.
KW - Chemotherapy
KW - Thymidylate synthase
KW - Time to progression
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U2 - 10.3816/CCC.2007.n.024
DO - 10.3816/CCC.2007.n.024
M3 - Article
C2 - 17681103
AN - SCOPUS:34547743173
SN - 1533-0028
VL - 6
SP - 572
EP - 577
JO - Clinical colorectal cancer
JF - Clinical colorectal cancer
IS - 8
ER -