Trial of Topotecan as First - Line Treatment for Ovarian Cancer Announced

SmithKline Beecham plans to launch a study of topotecan HCl, aninvestigational anticancer drug, in combination with cisplatin(Platinol) for the first-line treatment of ovarian cancer. Thedevelopment of this protocol was announced at the Eighth EuropeanConference on Clinical Oncology, Cancer Research and Cancer Nursing(ECCO-8) in Paris.

Topotecan currently is in the final stages of clinical developmentin Europe and the United States as a second-line, single agentfor the treatment of advanced ovarian and small-cell lung cancers.The company said that the decision to study the efficacy of topotecanin combination with cisplatin as a first-line treatment for ovariancancer was based on promising results of second-line studies.

"Topotecan has demonstrated promising efficacy in final andinterim results of several phase II and III studies," saidDr. Colin Broom, head of clinical development for oncology atSmithKline Beecham. "Based on these results, we are hopefulthat the addition of topotecan to first-line regimens will helpimprove outcomes for women battling ovarian cancer."

The new protocol will compare topotecan to paclitaxel (Taxol)when both agents are used in combination with cisplatin. "Wechose to compare topotecan with cisplatin to paclitaxel and cisplatin,as recent data suggest that the latter combination is the mosteffective regimen currently available," Dr. Broom said.

More than 40 oncologists and approximately 400 patients will beinvolved in the randomized, controlled study. The trial is scheduledto begin in major cancer centers throughout Europe in 1996, withcompleted enrollment anticipated in 1997.

Other Current Topotecan Trials

Current topotecan trials include a large, randomized, open-labelphase III study to compare topotecan with paclitaxel as second-linesingle agents for ovarian cancer. In an interim analysis of thisstudy, promising response rates have been observed. Final resultsare expected in 1996.

Topotecan's potential role in first-line, combination therapyfor ovarian cancer also is under investigation by the NationalCancer Institute in the United States.

Topotecan HCl is a novel anticancer agent that has demonstratedactivity against a variety of tumors in both preclinical and clinicalstudies. The drug is an analog of camptothecin, a plant alkaloidderived from the deciduous tree Camptotheca acuminata.

Topotecan belongs to an important new class of anticancer agentsthat selectively inhibit topoisomerase I. This nuclear enzymeis involved in cell proliferation, including DNA replication,DNA damage repair, and gene expression. Inhibition of topoisomeraseI by topotecan during replication produces DNA damage that resultsin the death of the proliferating tumor cells.