Clinical activity of irinotecan

Irinotecan (CPT11), a topoisomerase I inhibitor, is a new cytotoxic agent w ith a broad spectrum of clinical( activity. Two main schedules have been st udied and produce similar activity and side-effects: the "european" one - 3 50 mg/m(2) every 21 days-, and the "japanese-north american" one where CPT1 1 is given at a weekly dose of 100-120 mg/m(2) for 4 consecutive were follo wed by a 2 week rest period Activity was initially characterized in advance d colorectal cancers; response rates, disease free-survival and overall sur vival were 11%, 7-10 months and 8-11 months in patients failing fluoropyrim idine based chemotherapy - statistically improved as compared to best suppo rtive care and infusional flourouracil-, and 20-30% in patients not previou sly treated An interesting activity with response rates of 20-22% (increase d to 65% in combination with CDDP) has been shown in relapsed cervix carcin omas; 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 c ell lung cancer and esophagal carcinomas. Further studies are needed for ot her GI tract cancers, ovarian and head and neck carcinomas while minimal or no clinically meaningful activity has been reported in advanced breast can cer and haematological malignancies. Irinotecan can be combined to fluoropy rimidines, raltitrexed, cisplatin, carboplatin and oxaliplatin, to gemcitab ine, etoposide, vinorelbine and taxanes with flexible schedules (weekly, ev ery 2;weeks, every 21 days). Most of these combinations haved an additive o r supra additive activity. Its mechanism of action, the spectrum of activit y and the acceptable risk-benefit ratio point to irinotecan as a major adva nce in the field of cytotoxic anticancer therapy.