Evaluation of irinotecan in combination with 5-fluorouracil or etoposide in xenograft models of colon adenocarcinoma and rhabdomyosarcoma.

摘要: Irinotecan [7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptothec in] administered i.v. in two courses, each course consisting of administration every day for 5 days [(dx5)2] on 1-5 and 8-12, has demonstrated significant activity against advanced human tumor xenografts derived from colon adenocarcinomas several childhood cancers. To build this therapy, we have evaluated the combination irinotecan given schedule with 5-fluorouracil 1, 7, 14 or without leucovorin [(dx5)3 i.v.] tumors, combined etoposide (dx5)2 either 2 h before after treatment tumors rhabdomyosarcomas. A at 75% 50% their respective maximum tolerated doses when as single agents gave acceptable toxicity. Against adenocarcinoma xenografts, did not enhance response rate compared that obtained optimum dose a agent. GC3/TK- which lack thymidine kinase cannot salvage to circumvent inhibition thymidylate synthase, addition increased complete 10 >90%, whereas rates optimal 5-fluorouracil, agents, were 30 <10%, respectively. Etoposide d x three courses (d 5)3 p.o. cause objective regression any tumors. In contrast, five rhabdomyosarcoma lines high frequency partial regressions treated 5)1 Repetitive [e.g., 5)2 5)3] by 4-h infusion x3 equally effective less effective. using both drugs, was etoposide. Each drug could be only 38% its agent, indicating greater than additive Toxicity similar irrespective sequence manifested loss weight (73% initial weight, nadir 7), myelosuppression, prolonged thrombocytopenia. The responses carcinomas achieved alone same used combination. Similarly, irinotecan, rhabdomyosarcomas those irinotecan. However, experiments there antagonism antitumor