ASCO: Less Intense Therapy Maintains Survival and Reduces Toxicity in Neuroblastoma

CHICAGO, June 4 -- For infants and children with intermediate-risk neuroblastoma, a milder therapy regimen can preserve good long-term survival and minimize toxicity, found an international trial.

Three-year overall survival exceeded 90% with the less-intense treatment regimen, which improved on the favorable prognostic track record achieved with standard treatment protocols, reported David Baker, M.B.B.S., of Princess Margaret Hospital in Perth, Australia.

The investigational regimen also achieved the goal of minimizing toxicity, particularly renal, cardiac, and ototoxicity, Dr. Baker said at the American Society of Clinical Oncology meeting here.

"We were able to achieve an excellent cure rate with a remarkably significant reduction in therapy," said Dr. Baker. Compared with a historical control group, the patients had no decrement in survival with treatment durations that were reduced by as much as 70%.

The trial, which involved investigators in the U.S., Canada, Australia, and New Zealand, had the dual objective of achieving a three-year survival of more than 90% with less therapy. Enrollment was limited to infants and children with intermediate-risk neuroblastoma, defined by a combination of clinical and biologic factors. Eligible patients had nonamplification of the MYCN oncogene and were stratified on the basis of favorable or unfavorable biology.

The study enrolled 467 patients, comprising 362 infants and 105 children. All patients had surgery and chemotherapy. The regimens consisted of two or three agents from among carboplatin, doxorubicin, cyclophosphamide, and etoposide.

Dr. Baker said 192 patients with favorable biology received four cycles of chemotherapy lasting 64 days and 275 with unfavorable biology received eight cycles over 168 days. The shorter duration of treatment represented a 70% reduction compared with conventional chemotherapy lasting 268 days, and eight-cycle treatment was 40% briefer. The total number of treatment days was reduced from 71 with conventional therapy to 10 for patients with favorable biology and 18 for those with unfavorable biology.

Three-year overall survival was 96%, and event-free survival was 88%. In comparison, a historical control group of patients treated with more intense therapy had a three-year overall survival of 80% to 85%.

Dr. Baker reported that 69% of patients had reversible hematologic toxicity, and fewer than 2% had toxicity affecting major organ systems, particularly the kidneys, heart, and hearing. Fifteen patients (3%) died on study, including only four patients (0.8%) who died of treatment-related infections.

"We feel this reduction of therapy approach represents further progress toward our goal of increasing cure with a reduction in the burden and cost of cure," said Dr. Baker.