Topotecan
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00-Aug-2007 - Topotecan shows promise against Wilms tumor
Topotecan shows promise against Wilms tumor
Monika Metzger, MD
St. Jude researchers have shown that the drug topotecan holds promise as a treatment for the recurrent form of a kidney cancer called Wilms tumor, a solid tumor of the kidney that arises from immature kidney cells, and the fifth most common tumor among children. The investigators recommend further evaluation of this promising anticancer drug as it may even be more effective if given to children at the time of first relapse, rather than after having received many different salvage regimens.
Recurrent tumors are those that return after initial treatment. Favorable histology means that the tumor, when treated with modern therapies, is associated with good outcome.
The finding is important because although effective treatment of Wilms tumor is one of the great success stories in cancer therapy, not all children do well after an initial treatment. The rate of survival among children whose cancer has returned following initial treatment is about 30 to 60 percent, depending on the treatment they receive, according to Monika Metzger, MD, Oncology. Metzger is lead author of a report on this work that was published in the July 20 issue of Journal of Clinical Oncology.
“We need new agents for improving the survival rate of children with recurrent or anaplastic histology Wilms tumor,” said Najat Daw, MD, Oncology. “We studied the efficacy of topotecan against this cancer because it’s effective against various other pediatric solid tumors, such as neuroblastoma and medulloblastoma. And previous studies at St. Jude have shown that mouse models of Wilms tumor respond to this drug.” Anaplastic cells are those that have lost specific characteristics of their cell type.
Based on these findings and the promising results of Phase I studies, the St. Jude team conducted a multi-institutional Phase II study called WILTOP to estimate the response rate of topotecan among patients with recurrent Wilms tumor. The other institutions included Dana Farber Cancer Institute (Boston), Alberta Children’s Hospital (Canada), Children’s Hospital of Atlanta (Georgia) and the Hospital for Sick Children in Toronto (Canada).
Patients were eligible for this study if they had recurrent or progressive favorable histology Wilms tumor after primary treatment and at least one attempt at a previous standard salvage treatment; or if they had recurrent or progressive anaplastic histology Wilms tumor after primary treatment.
Anaplastic cells divide rapidly and bear little resemblance to normal cells, as is characteristic of cancer; this form of Wilms tumor is associated with poor outcome. Salvage therapy is treatment given if a tumor fails to respond to other treatments, or after a tumor returns following standard treatment.
The investigators found that 12 of the 25 children with favorable histology Wilms tumor showed a partial response to topotecan, as did two out of 11 children with anaplastic histology.
“The response rate among children with favorable histology Wilms was promising because those patients had been heavily pretreated before this trial and their disease progressed even after at least one attempt at salvage chemotherapy,” Metzger said. “That gives us some hope that topotecan can improve the survival rate in patients with recurrent Wilms tumor if they receive the drug earlier in their therapy.”
The small number of patients with anaplastic histology Wilms tumor made it impossible to determine whether topotecan is effective in these patients, Metzger noted. But the fact that even two patients did respond to this treatment-resistant form of the tumor is encouraging, she added.
“The current treatment for Wilms tumor is satisfactory for most patients,” Metzger said. “But in the future, we might be able to identify patients who can benefit from topotecan because they are at very high risk of failing therapy. We’d like to save all our patients, and Topotecan might bring us closer to that goal.”
Other St. Jude authors of the study include Catherine Billups and Jianrong Wu, PhD, Biostatistics; Clinton Stewart, PharmD, Pharmaceutical Sciences; and former St. Jude employees Burgess Freeman and Fredric Hoffer, MD. Jeffrey Dome, MD, the senior author, is now chief of Pediatric Oncology at Children’s National Medical Center in Washington, DC.
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