The Clinical and Diagnostic Trials Section provides full statistical suppor for the Brain Tumor Cooperative Group (BTCG), a multicenter group of neurosurgeons, neuro-oncologists, radiotherapists, neuro-radiologists, and neuro-pathologists conducting randomized trials for patients with primary brain tumors (with emphasis on malignant gliomas). In 1994, the BTCG completed accrual of patients to a randomized phase III trial, BTCG 87- 01, investigating interstitial radiation (seed implants) added to the customary external beam radiation and IV BCNU chemotherapy. Preliminary analyses have been performed and the results presented. Patients randomized to interstitial radiation had increased survival compared to the standard arm. As with past studies, age, Karnofsky performance status, and histopathology were found to be significant prognostic factors. Models adjusting for these factors suggested that the treatment difference in favor of interstitial radiation occurred for glioblastoma multiforme but not for the other malignant gliomas; this latter subgroup had small numbers, and differences here were not statistically significant. Pathology review at the surgery following possible """"""""failure"""""""" showed that categorization by viable tumor versus necrosis (+/- tumor cells) was significantly predictive of subsequent survival. Followup has continued on all patients on BTCG 87-01. During 1994, accrual was completed on another randomized trial, BTCG 89-01, comparing two phase III chemotherapy regimens given in addition to surgery and radiotherapy: the standard IV BCNU vs. the combination of IV BCNU with intra-arterial cisplatin. The trial had also included a third arm in the randomization, used to investigate, successively, new investigational phase II drugs. The initial agent was edatrexate; when accrual for this group was completed in early 1992, randomization was begun to piroxantrone. Accrual to this third arm was terminated early by the Division of Cancer Treatment (who funds the BTCG and is responsible for all official NCI decision-making for these trials), because of a decision not to pursue the agent piroxantrone. Followup continues on all patients on BTCG 89-01, with appropriate data monitoring. Final analyses of two older BTCG phase II trials have recently been published. Trial 81-20 showed a survival advantage to the group randomized to PCNU compared to AZQ. Trial 84-20A showed a survival advantage to the group randomized to PCNU compared to intra- arterial cisplatin, although the difference was modest. Together, these trials suggest that PCNU is an active drug for brain tumors.
