SmithKline Beecham plans to launch a study of topotecan(Drug information on topotecan) HCl, an investigational anticancer drug, in combination with cisplatin(Drug information on cisplatin) (Platinol) for the first-line treatment of ovarian cancer. The development of this protocol was announced at the Eighth European Conference on Clinical Oncology, Cancer Research and Cancer Nursing (ECCO-8) in Paris.
Topotecan currently is in the final stages of clinical development in Europe and the United States as a second-line, single agent for the treatment of advanced ovarian and small-cell lung cancers. The company said that the decision to study the efficacy of topotecan in combination with cisplatin as a first-line treatment for ovarian cancer was based on promising results of second-line studies.
"Topotecan has demonstrated promising efficacy in final and interim results of several phase II and III studies," said Dr. Colin Broom, head of clinical development for oncology at SmithKline Beecham. "Based on these results, we are hopeful that the addition of topotecan to first-line regimens will help improve outcomes for women battling ovarian cancer."
The new protocol will compare topotecan to paclitaxel(Drug information on paclitaxel) (Taxol) when both agents are used in combination with cisplatin. "We chose to compare topotecan with cisplatin to paclitaxel and cisplatin, as recent data suggest that the latter combination is the most effective regimen currently available," Dr. Broom said.
More than 40 oncologists and approximately 400 patients will be involved in the randomized, controlled study. The trial is scheduled to begin in major cancer centers throughout Europe in 1996, with completed enrollment anticipated in 1997.
Other Current Topotecan Trials
Current topotecan trials include a large, randomized, open-label phase III study to compare topotecan with paclitaxel as second-line single agents for ovarian cancer. In an interim analysis of this study, promising response rates have been observed. Final results are expected in 1996.
Topotecan's potential role in first-line, combination therapy for ovarian cancer also is under investigation by the National Cancer Institute in the United States.
Topotecan HCl is a novel anticancer agent that has demonstrated activity against a variety of tumors in both preclinical and clinical studies. The drug is an analog of camptothecin, a plant alkaloid derived from the deciduous tree Camptotheca acuminata.
Topotecan belongs to an important new class of anticancer agents that selectively inhibit topoisomerase I. This nuclear enzyme is involved in cell proliferation, including DNA replication, DNA damage repair, and gene expression. Inhibition of topoisomerase I by topotecan during replication produces DNA damage that results in the death of the proliferating tumor cells.