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| |  ASCO MEETING: Bone Marrow Transplant And Vitamin A Derivative Improve Neuroblastoma Survival LOS ANGELES, CA -- May 19, 1998 -- Two innovative treatments -- bone marrow transplant and follow-up therapy with high doses of retinoic acid, a derivative of Vitamin A -- significantly improve the disease-free survival of children with high-risk neuroblastoma, the third most common childhood cancer. Researchers at the University of California-San Francisco and Children’s Hospital Los Angeles, working with the United States-wide Children's Cancer Group, reported those findings from a randomised study of 539 children in two separate sessions at the annual meeting of the American Society for Clinical Oncology yesterday. "The improved survival rates came without a significant increase in toxic side effects or extra days in the hospital. We recommend that these therapies should be incorporated into future treatment regimens," said Katherine Matthay, M.D., director of the Children's Cancer Group neuroblastoma study, professor of pediatrics at the University of California San Francisco and director of pediatric clinical oncology for Lucile Packard Children's Health Services at UCSF. Matthay reported at ASCO on the bone marrow transplant results. C. Patrick Reynolds, MD, PhD, of Childrens Hospital Los Angeles (CHLA), reported on the retinoic acid stage of the trial. Reynolds is associate professor of pediatrics and pathology at the University of Southern California School of Medicine. The study, a Phase III randomised trial designed to test the efficacy of the treatment, began in 1991 and was conducted at more than 100 medical centres. It showed a significant increase in event-free survival for children who received autologous purged bone marrow transplants. Results were even more dramatic for those whose initial therapy was followed up with high doses of 13-cis retinoic acid, a Vitamin A derivative commonly prescribed for acne under the trade name Accutane. Most dramatic of all were results for a combination of the two treatments: 55 percent of the children who received bone marrow transplants survived free of relapse for three years after beginning follow-up treatment with retinoic acid. That rate compares to 16 percent for children treated with consolidation chemotherapy alone. Neuroblastoma is a cancer of the sympathetic nervous system. The most common solid tumour, other than brain tumours, to occur in children, it rarely strikes adults. The average age of diagnosis is two-and-a-half years and one in 6,000 children are diagnosed with neuroblastoma by the age of five. The patients who received treatment as part of the Children's Cancer Group Study were at high risk -- the majority had tumours that had metastasised to other sites. The 539 children were treated with induction chemotherapy for five months, then surgery to remove their tumours. The surgery was followed either by a state-of-the-art therapy consisting of three cycles of intensive consolidation chemotherapy, or by chemoradiotherapy followed by purged autologous bone marrow transplants. In the latter treatment, part of the child's own bone marrow is harvested and purged of all cancer cells. The remaining bone marrow is destroyed by chemotherapy and radiation, then the frozen marrow is thawed and re-infused back into the patient to produce a cancer-free immune system. Reynolds' group at CHLA cleansed the bone marrow for all the transplant recipients in this study. Matthay reported that from a point eight weeks after diagnosis, 34 percent of the bone marrow transplant patients survived three years without a return of cancer, compared with 21 percent for those who received three cycles of intensive consolidation chemotherapy. "This study shows that purged autologous bone marrow transplant after high dose chemoradiotherapy provides the best chance of survival in advanced neuroblastoma," Matthay said. In the next stage of the trial, 129 patients who had received either consolidation chemotherapy or bone marrow transplants were given an additional course of high-dose 13-cis retinoic acid. The three-year event-free survival rate for children who received retinoic acid after either of the two intensive therapies was 47 percent. In comparison, 25 percent of the patients who received no further therapy survived three years with no recurrence of cancer. This is the first randomised study to show that 13-cis retinoic acid is effective in treating neuroblastoma in patients with a poor survival prognosis. Matthay and Reynolds credit the Children's Cancer Group for the large-scale co-operative effort that made this study possible. Neuroblastoma is rare enough that it required co-ordination among many medical centres to conduct a randomised trial, they said.
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