The relevance of drug sequence in combination chemotherapy Journal Article


Authors: Shah, M. A.; Schwartz, G. K.
Article Title: The relevance of drug sequence in combination chemotherapy
Abstract: The concept of combining chemotherapeutic agents to increase the cytotoxic efficacy has evolved greatly over the past several years. In the past, the rationale for combination chemotherapy centered on attacking different biochemical targets, overcoming drug resistance in heterogenous tumors, and increasing the dose-density of combination chemotherapy to take advantage of tumor growth kinetics. The overall goal was to improve clinical efficacy with acceptable clinical toxicity. It is now apparent that the sequence of drug administration can significantly enhance the therapeutic effect of chemotherapy. These sequence-dependent effects can be explained by chemotherapy-induced cell cycle perturbations, or by pharmacodynamic interactions between the agents in combination. In this review, we focus on drug combinations with taxanes and camptothecins, which we believe best illustrate the importance of the cell cycle and pharmacologic interactions in the sequential administration of chemotherapy. As our understanding of the cell cycle grows, our ability to appropriately sequence chemotherapy can have a great impact on the treatment of human cancers. © 2000 Harcourt Publishers Ltd.
Keywords: review; fluorouracil; cancer combination chemotherapy; dose response; drug efficacy; paclitaxel; methotrexate; cell cycle; pharmacodynamics; etoposide; docetaxel; platinum; vinca alkaloid; drug cytotoxicity; taxane derivative; tumor growth; anthracycline derivative; camptothecin derivative; tumor resistance; raltitrexed; 7 hydroxystaurosporine; priority journal
Journal Title: Drug Resistance Updates
Volume: 3
Issue: 6
ISSN: 1368-7646
Publisher: Harcourt Publishers Ltd  
Date Published: 2000-12-01
Start Page: 335
End Page: 356
Language: English
DOI: 10.1054/drup.2000.0165
PROVIDER: scopus
PUBMED: 11498402
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
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  1. Gary Schwartz
    385 Schwartz
  2. Manish Shah
    177 Shah