Topotecan, an active new antineoplastic agent: review and current status

Abstract

Topotecan (Hycamtin™) is a water soluble semisynthetic analogueof the alkaloid camptothecin which has antitumouractivity in preclinical models in vitro and in vivo. A range ofPhase I studies has been performed and a daily x 5 iv. schedule,which showed most promising evidence of activity, was selectedfor extensive clinical evaluation. To date, topotecan hasbeen shown to be active in a number of malignancies, includingmetastatic ovarian cancer, recurrent small cell lung cancer(SCLC), non-small cell lung cancer (NSCLC), breast cancer,colorectal cancer and myelodysplastic syndrome. In ovariancancer, response rates of around 15% were identified in patientswho had failed standard chemotherapy, and in a randomised,comparative study with paclitaxel response rates of 20% (topotecan)and 13% (paclitaxel) were observed. In addition, overalltime to progression was impressive at 23 weeks (topotecan)compared with 14 weeks (paclitaxel). In recurrent SCLC, topotecanhas shown good activity in sensitive patients with aresponse rate of 39%, although the response rate in refractorypatients was considerably lower (7%). Median survival of allpatients was 5.4 months, acceptable for this difficult clinicalscenario. Topotecan is well-tolerated in the majority of patientsand subjective toxicities are uncommon. The principal side-effectis myelosuppression, mainly neutropenia. Serious clinicalsequelae are relatively uncommon and non-cumulative. Nonhaematologicaltoxicities are generally mild and not dose-limiting.In clinical use, topotecan has exhibited activity in multipletumour types, with a side-effect profile that is predictable andmanageable. The drug is under evaluation in other tumour typesand in combination chemotherapy regimens.