Antitumor efficacy of edotecarin in combination with other cytotoxic drugs.

2099 Edotecarin is an indolocarbazole derivative, more potent than camptothecin in inhibiting topoisomerase I and active in a panel of in vitro and in vivo human tumor models (Yoshinari et al, Cancer Res. 1999; Arakawa et al, Jpn. J. Cancer Res. 1999). When tested in vitro, edotecarin showed synergism with cisplatin, carboplatin and oxaliplatin. The synergy observed in combination with cisplatin was confirmed also in vivo against the P388 leukemia model and the HCT-116 human colon carcinoma model, with both treatments administered on the same days with 1-h interval. When tested with a similar schedule on the same HCT-116 model, also the combination with CPT-11 showed an antitumor efficacy higher than that observed with the two compounds as single agents. Synergistic activity with docetaxel was observed on the SKBR-3 human breast carcinoma model when edotecarin was administered after the taxane with a 24-h interval. As far as the combination with 5-FU is concerned, the schedule with a 72-96 h interval between drugs presented the highest improvement of the antitumor activity in comparison with the single drugs. No toxicity was reported in any of the presented combinations.