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.
"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
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.