PMID: 9194475Apr 1, 1997Paper

Combination chemotherapy studies with gemcitabine

Seminars in Oncology
C J van MoorselGodefridus J Peters

Abstract

Gemcitabine (2',2'-difluorodeoxycytidine) is an antineoplastic agent with clinical activity against ovarian carcinoma, small cell and non-small cell lung cancers, head and neck cancer, bladder cancer, breast cancer, and pancreatic cancer. Cisplatin (CDDP), etoposide (VP-16), and mitomycin C (MMC) are well-known anticancer agents that are also active against many of these types of cancer. Because of the low toxicity profile of gemcitabine and the differences in mechanism of cytotoxicity, combinations of these drugs with gemcitabine were studied in vitro and in vivo. Cells were exposed in vitro for 1, 4, 24, or 72 hours to gemcitabine in combination with these drugs, either simultaneously or sequentially in a constant ratio. Another approach consisted of exposure to a combination of the approximate IC25 of one drug and varying concentrations of the other drug. Synergism for several of these combinations was found in the human ovarian cancer cell line A2780, its CDDP-resistant variant ADDP, its gemcitabine-resistant variant AG6000, and in the non-small cell lung cancer cell lines H322 and Lewis lung (LL) after a 72-hour drug treatment. Studies of the possible mechanisms of action initially focused on the major metabolic features o...Continue Reading

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