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 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.
According to a new study published in the October 1, 1996, issueof Blood, Hycamtin (topotecan hydrochloride) offers a promisingnew treatment option for patients suffering from myelodysplasticsyndrome (MDS) and chronic myelomonocytic leukemia (CMML). Patientstreated with topotecan achieved a complete response rate of 28%,while currently used single-agent therapies have traditionallyachieved a complete response rate of only 10% to 15% among thishigh-risk patient group. Topotecan, a topoisomerase I inhibitormarketed by SmithKline Beecham, is currently indicated for thetreatment of patients with recurrent, metastatic ovarian cancer.
"These results are very encouraging. Hycamtin appears tobe nearly twice as effective as traditional treatments, even amongpatients with poor prognoses. We attribute these results to thedrug's new mechanism of action which is completely different fromthat of other agents active in myeloid malignancies," commentedMiloslav Beran, md, phd, professor of medicine, leukemia section,department of hematology, The University of Texas M. D. AndersonCancer Center, and lead author of the study.
Myelodysplastic syndrome and chronic myelomonocytic leukemia areblood disorders characterized by an abnormal maturation of bonemarrow cells. Patients with CMML also have a dangerously highwhite blood cell count. Both diseases are most common in individualsover the age of 60. In total, there are an estimated 120,000 leukemiapatients in the United States. An estimated 27,600 new cases ofleukemia will be diagnosed this year, and 21,000 people will diefrom this disease.
In this study, 22 patients with MDS and 25 patients with CMMLreceived topotecan, 2 mg/m2 intravenously over 24 hours dailyfor 5 days every 3 to 4 weeks until remission, and then once everymonth for a maximum of 12 courses. A complete response was definedas peripheral blood with 5% or less marrow blasts and the normalizationof hemoglobin, platelets, and white blood cells for at least 4weeks. A total of 28% of patients achieved a complete response.
In previous studies involving MDS and CMML patients who receivedother chemotherapies, rates of complete response to treatmenthave been disappointing. "MDS and CMML are very difficultto treat. Until now the benefits of chemotherapy have been questionable,so there has been no standard of care or generally accepted treatmentregimen for this patient population. The potential use of Hycamtinlooks promising for MDS and CMML patients, as well as other leukemiapatients," said Dr. Beran.
Other Studies Underway
At M. D. Anderson, studies are underway involving the use of topotecanin combination with other chemotherapies among a similar patientpopulation and as a single-agent therapy for the treatment ofchronic myelogenous leukemia, which strikes about 6,000 Americanseach year. Topotecan is also being studied elsewhere for use inthe treatment of acute and chronic leukemia.
As with many chemotherapeutic agents, the main side effect demonstratedby topotecan in this study was suppression of white blood cellsproduced in the bone marrow. The most frequently reported sideeffects with topotecan at this dosage were mucositis, diarrhea,nausea and vomiting, and eight deaths were attributable to myelosuppression-associatedcomplications.
In May 1996, topotecan became the first topoisomerase I inhibitorto be cleared for marketing by the FDA. It is indicated for thetreatment of patients with recurrent, metastatic ovarian cancerat 1.5 mg/m2 administered intravenously over 30 minutes dailyfor 5 days. This new class of drugs kills cancer cells by inhibitingthe enzyme topoisomerase I, which is essential for the replicationof DNA in human cells.
Topotecan is under clinical investigation for a number of othercancers, including small-cell lung, breast, and colorectal cancers.The drug also is being studied as a component of first-line combinationchemotherapy in patients with ovarian cancer.