[Clinical activity spectrum of irinotecan]

Irinotecan (CPT11), a topoisomerase I inhibitor, is a new cytotoxic agent with a broad spectrum of clinical activity. Two main schedules have been studied and produce similar activity and side-effects: the "european" one--350 mg/m2 every 21 days-, and the "japanese-north american" one where CPT11 is given at a weekly dose of 100-120 mg/m2 for 4 consecutive weeks followed by a 2 week rest period. Activity was initially characterized in advanced colorectal cancers; response rates, disease free-survival and overall survival were 11%, 7-10 months and 8-11 months in patients failing fluoropyrimidine based chemotherapy--statistically improved as compared to best supportive care and infusional fluorouracil-, and 20-30% in patients not previously treated. An interesting activity with response rates of 20-22% (increased to 65% in combination with CDDP) has been shown in relapsed cervix carcinomas; in gastric carcinomas response rates of 20% have been shown, reaching 48% in combination with CDDP. Response rates of 20-22%, increased to 40-60% when irinotecan was associated to CDDP have been reported in non small cell lung cancer and esophagal carcinomas. Further studies are needed for other GI tract cancers, ovarian and head and neck carcinomas while minimal or no clinically meaningful activity has been reported in advanced breast cancer, and haematological malignancies. Irinotecan can be combined to fluoropyrimidines, raltitrexed, cisplatin, carboplatin and oxaliplatin, to gemcitabine, etoposide, vinorelbine and taxanes with flexible schedules (weekly, every 2 weeks, every 21 days. Most of these combinations have an additive or supra additive activity. Its mechanism of action, the spectrum of activity and the acceptable risk-benefit ratio point to irinorecan as a major advance in the field of cytotoxic anticancer therapy.