Commentary: a case for minimizing folate supplementation in clinical regimens with pemetrexed based on the marked sensitivity of the drug to folate availability.

Commentary: a case for minimizing folate supplementation in clinical regimens with pemetrexed based on the marked sensitivity of the drug to folate availability. Research Abstract Details 

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Commentary: a case for minimizing folate supplementation in clinical regimens with pemetrexed based on the marked sensitivity of the drug to folate availability. Abstract Text:

Shrikanta Chattopadhyay,Roni Tamari,Sang H Min,Rongbao Zhao,Eugenia Tsai,I David Goldman,Shrikanta Chattopadhyay,Roni Tamari,Sang H Min,Rongbao Zhao,Eugenia Tsai,I David Goldman,

Pemetrexed is a novel antifolate recently approved for the treatment of pleural mesothelioma and non-small cell lung cancer. In clinical regimens, pemetrexed is administered in conjunction with folic acid to minimize toxicity. However, excessive folate supplementation may also diminish the activity of this agent. The current study demonstrates, in several human solid tumor cell lines, that when extracellular 5-formyltetrahydrofolate levels are increased in vitro, within the range of normal human blood levels, there is a substantial decrease in pemetrexed activity upon continuous exposure to the drug. This was accompanied by a comparable lower level of trimetrexate activity consistent with an expansion of tumor cell folate pools. Likewise, when cells were exposed to pemetrexed with a schedule that simulates in vivo pharmacokinetics, there was markedly less cell killing with higher extracellular folate levels. Data are provided to indicate that 5-formyltetrahydrofolate is an acceptable surrogate for 5-methyltetrahydrofolate, the major blood folate, for this type of in vitro study. These observations and other reports suggest that, in view of the rise in serum folate and fall in serum homocysteine that has accompanied folic acid supplementation of food in the U.S., the addition of folic acid to regimens with pemetrexed should be limited to the lowest recommended level that provides optimal protection from pemetrexed toxicity.

Commentary: a case for minimizing folate supplementation in clinical regimens with pemetrexed based on the marked sensitivity of the drug to folate availability. Publishing Authors By Initials

S Chattopadhyay,R Tamari,SH Min,R Zhao,E Tsai,ID Goldman,S Chattopadhyay,R Tamari,SH Min,R Zhao,E Tsai,ID Goldman,

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Commentary: a case for minimizing folate supplementation in clinical regimens with pemetrexed based on the marked sensitivity of the drug to folate availability. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The oncologist

VOLUME: 12

Page Numbers: 808-15

Journal Abbreviation: Oncologist

ISSN: 1083-7159

DAY: 3

MONTH: Jul

YEAR: 2007

Commentary: a case for minimizing folate supplementation in clinical regimens with pemetrexed based on the marked sensitivity of the drug to folate availability. Information

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LANGUAGE: eng

NlmUniqueID: 9607837

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Grant and Affiliation Information for Commentary: a case for minimizing folate supplementation in clinical regimens with pemetrexed based on the marked sensitivity of the drug to folate availability.

AFFILIATION: Department of Medicine, The Albert Einstein College of Medicine Cancer Center, Bronx, NY 10461, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA82621

ACRONYM: CA

MEDLINETA: Oncologist

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