According to a new study published in the October 1, 1996, issue of Blood, Hycamtin (topotecan hydrochloride) offers a promising new treatment option for patients suffering from myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). Patients treated with topotecan(Drug information on topotecan) achieved a complete response rate of 28%, while currently used single-agent therapies have traditionally achieved a complete response rate of only 10% to 15% among this high-risk patient group. Topotecan, a topoisomerase I inhibitor marketed by SmithKline Beecham, is currently indicated for the treatment of patients with recurrent, metastatic ovarian cancer.
"These results are very encouraging. Hycamtin appears to be nearly twice as effective as traditional treatments, even among patients with poor prognoses. We attribute these results to the drug's new mechanism of action which is completely different from that of other agents active in myeloid malignancies," commented Miloslav Beran, md, phd, professor of medicine, leukemia section, department of hematology, The University of Texas M. D. Anderson Cancer Center, and lead author of the study.
Myelodysplastic syndrome and chronic myelomonocytic leukemia are blood disorders characterized by an abnormal maturation of bone marrow cells. Patients with CMML also have a dangerously high white blood cell count. Both diseases are most common in individuals over the age of 60. In total, there are an estimated 120,000 leukemia patients in the United States. An estimated 27,600 new cases of leukemia will be diagnosed this year, and 21,000 people will die from this disease.
In this study, 22 patients with MDS and 25 patients with CMML received topotecan, 2 mg/m2 intravenously over 24 hours daily for 5 days every 3 to 4 weeks until remission, and then once every month for a maximum of 12 courses. A complete response was defined as peripheral blood with 5% or less marrow blasts and the normalization of hemoglobin, platelets, and white blood cells for at least 4 weeks. A total of 28% of patients achieved a complete response.
In previous studies involving MDS and CMML patients who received other chemotherapies, rates of complete response to treatment have been disappointing. "MDS and CMML are very difficult to treat. Until now the benefits of chemotherapy have been questionable, so there has been no standard of care or generally accepted treatment regimen for this patient population. The potential use of Hycamtin looks promising for MDS and CMML patients, as well as other leukemia patients," said Dr. Beran.
Other Studies Underway
At M. D. Anderson, studies are underway involving the use of topotecan in combination with other chemotherapies among a similar patient population and as a single-agent therapy for the treatment of chronic myelogenous leukemia, which strikes about 6,000 Americans each year. Topotecan is also being studied elsewhere for use in the treatment of acute and chronic leukemia.
As with many chemotherapeutic agents, the main side effect demonstrated by topotecan in this study was suppression of white blood cells produced in the bone marrow. The most frequently reported side effects with topotecan at this dosage were mucositis, diarrhea, nausea and vomiting, and eight deaths were attributable to myelosuppression-associated complications.
In May 1996, topotecan became the first topoisomerase I inhibitor to be cleared for marketing by the FDA. It is indicated for the treatment of patients with recurrent, metastatic ovarian cancer at 1.5 mg/m2 administered intravenously over 30 minutes daily for 5 days. This new class of drugs kills cancer cells by inhibiting the enzyme topoisomerase I, which is essential for the replication of DNA in human cells.
Topotecan is under clinical investigation for a number of other cancers, including small-cell lung, breast, and colorectal cancers. The drug also is being studied as a component of first-line combination chemotherapy in patients with ovarian cancer.