Efficacy of oral irinotecan against neuroblastoma xenografts

Anti-cancer Drugs
J ThompsonP J Houghton

Abstract

The efficacy of the topoisomerase I inhibitor, 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxy-camptotheci n (irinotecan, CPT-11), administered by oral gavage has been examined against a panel of six independently derived neuroblastoma xenografts. Irinotecan was administered either daily for 5 days on 12 consecutive weeks ¿(d x 5)12¿ or for 5 days on two consecutive weeks repeated every 21 days for 4 cycles ¿[(d x 5)2]4¿. Given on the (d x 5)12 schedule the maximum tolerated dose (MTD) was 50 mg/kg. For intermittent scheduling ¿[(d x 5)2]4¿, the MTD was 75 mg/kg, resulting in the same total dose being administered (3 g/kg) over the period of treatment. At the MTD for the 12 consecutive week schedule there were two of 42 toxicity related deaths, whereas intermittent scheduling at the MTD resulted in none of 42 deaths. The intermittent schedule ¿[(d x 5)2]4¿ was less toxic than therapy given (d x 5)12, as at the end of treatment mice weighed 92 +/- 4% (SD; n = 6 experiments) and 81 +/- 4% (SD; n = 6 experiments) of their body weight at the start of therapy, respectively. The latter schedule was associated with loose feces starting around week 8 of therapy, broken teeth and a high incidence of swelling of the orbital conjun...Continue Reading

Citations

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