PEDIATRIC PHASE-II CANCER-CHEMOTHERAPY TRIALS - A PEDIATRIC-ONCOLOGY-GROUP STUDY

Purpose: This study reviewed the Pediatric Oncology Group experience w ith phase II clinical trials in children (<21 years of age) with refra ctory tumors. Patients and Methods: Patients registered in Pediatric O ncology Group phase II studies were evaluated. Patients had to be <21 years of age with recurrent and refractory measurable disease. Tumor t ypes and response rates were determined. Death on therapy from either drug toxicity, progressive disease, infection, or hemorrhage was measu red. Tumor-specific, disease-free survival curves were calculated by K aplan-Meier analysis. Results: Between 1984 and 1994, 2,465 patient en tries were made on 45 phase II trials. Malignancies registered include d acute lymphocytic leukemia (ALL) (16.7%), acute myeloid leukemia (AM L) (22.0%), osteogenic sarcoma (7.8%), neuroblastoma (7.2%), astrocyto ma (7.2%), medulloblastoma (7.1%), glioma (6.7%), ependymoma (6.1%), a nd others (29.2%). The overall response rate was 19.6% (CR + PR) for c hildren entered on phase II trials. Tumor-specific response rates rang ed from 62.1% (23/37) for children with Hodgkin's disease to no respon ses (0/23) in patients with hepatoblastoma. When comparing single vers us multiagent trials, a significantly better initial response rate was seen in the latter studies. However, 5-year survival was comparable. Progression-free survival for all tumor histologies were 12.9% and 9.2 % at 2 and 5 years, respectively. Death on study was seen in 11.6% of the patients; however, only three deaths were directly related to drug toxicity. There were no significant gender differences in regards to response, progressive disease, or death on study. Conclusion: Phase II studies conducted in children offer a considerable likelihood of ther apeutic benefit without exposing these patients to untoward toxicity.