Hycamtin in the therapy of non-small-cell lung cancer

In the previously conducted phase I/II studies, topotecan has proved its efficacy in advanced non-small-cell lung cancer. Given alone, the use of 1.5 mg/m(2) as a short infusion from day 1 to 5 every 3 weeks proved practicable and effective. Myelosuppression, in particular neutropenia, is thus the dose-limiting toxicity, albeit of only short duration and without any notable rate of septic complications. The response rates found in the previously available phase II studies on monotherapy ranged between 4 and 24%. Other therapy regimens with continuous infusion for 3 or 21 days proved to be less effective and would therefore not tend to be suited for investigation. This would apply to combination treatments as well. In combination with other agents it was shown that, although the efficacy obtained on topotecan in combination with cisplatin was good, the toxicity was also high. Neutropenia ranked as the major toxicity. The sequence of administering cisplatin and topotecan had clearly an effect on toxicity. When cisplatin was given before topotecan, the bone marrow toxicity proved to be greater than when cisplatin was given after topotecan. The combination of topotecan plus carboplatin at a dosage of AUC 4 is also possible. Likewise. the sequence of administering the two agents is important. When the administration of topotecan was delayed after carboplatin, this proved superior to simultaneous administration. In a randomized phase II study, the combination of topotecan and paclitaxel also proved efficacious, although response rate, median survival and 1-year survival were not substantially different from the corresponding values of any other of the standard combinations used to date. The results in locally advanced tumors of stages IIIA and IIIB are encouraging and merit further evaluation. In total, topotecan in future must also be tested in phase III studies in comparison to the previous standard therapies, in order to establish their final rank in the anticancer arsenal.