Topotecan shows Promise against Wilms Tumour

St. Jude researchers have shown that the drug topotecan holds promise as a treatment for the recurrent form of a kidney cancer called Wilms tumour, a solid tumour of the kidney that arises from immature kidney cells, and the fifth most common tumour 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 tumours are those that return after initial treatment. Favourable histology means that the tumour, when treated with modern therapies, is associated with good outcome.The finding is important because although effective treatment of Wilms tumour 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 tumour,” said Najat Daw, MD, Oncology. “We studied the efficacy of topotecan against this cancer because it’s effective against various other pediatric solid tumours, such as neuroblastoma and medulloblastoma. And previous studies at St. Jude have shown that mouse models of Wilms tumour 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 tumour. 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 favourable histology Wilms tumour after primary treatment and at least one attempt at a previous standard salvage treatment; or if they had recurrent or progressive anaplastic histology Wilms tumour after primary treatment.Anaplastic cells divide rapidly and bear little resemblance to normal cells, as is characteristic of cancer; this form of Wilms tumour is associated with poor outcome. Salvage therapy is treatment given if a tumour fails to respond to other treatments, or after a tumour returns following standard treatment.The investigators found that 12 of the 25 children with favourable histology Wilms tumour showed a partial response to topotecan, as did two out of 11 children with anaplastic histology.”The response rate among children with favourable 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 tumour if they receive the drug earlier in their therapy.”The small number of patients with anaplastic histology Wilms tumour 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 tumour is encouraging, she added.”The current treatment for Wilms tumour 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.(Source: Journal of Clinical Oncology : St. Jude Children’s Research Hospital : October 2007)