PMID: 9194474Apr 1, 1997Paper

In vitro interaction between gemcitabine and other anticancer drugs using a novel three-dimensional model

Seminars in Oncology
F Kanzawa, N Saijo

Abstract

Gemcitabine (2',2'-difluorodeoxycytidine) is a deoxycytidine analog with significant antitumor activity against ovarian cancer and non-small cell lung cancer. It is a suitable candidate for combination chemotherapy in non-small cell lung cancer for three reasons: it is active as a single agent, it has no overlapping toxicities with other chemotherapeutic agents, and it has different mechanisms of action compared with other anticancer drugs. We therefore investigated the combination effects between gemcitabine and other anticancer drugs on the growth of the non-small cell lung cancer cell line, PC-14. Combination effects were analyzed by means of a three-dimensional model, which directly elucidates the shape of the dose-response surface over the entire clinical dose range, identifies regions of statistically significant synergy and antagonism, and quantifies these effects. The three-dimensional analysis clearly demonstrates a relationship, the nature of which depends on the concentration of both drugs. A synergistic effect was observed when gemcitabine and cisplatin were combined at concentrations of 0.0005 to 0.001 microg/mL and 0.025 to 0.25 microg/mL, respectively. In combination with vindesine, a remarkable synergistic inter...Continue Reading

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