CARBOPLATIN IN CHILDHOOD MEDULLOBLASTOMA PNET - FEASIBILITY OF AN IN-VIVO SENSITIVITY TEST IN AN UP-FRONT STUDY

Sixteen patients with high risk MB/PNET at diagnosis were included in a pilot study employing carboplatin (CBDCA) as a single drug prior to conventional therapy. The main goal of the study was to identify in a short-term trial a significant response that would predict further res ponse to CBDCA in the single patient. Exploration of CBDCA activity wa s focused on response after the first course as compared to the respon se following the second course. A course consisted of CBDCA 600 mg/m2 on days 1 and 2 administered in a 1 h infusion to be repeated 3-4 week s later. After two cycles we observed 1 CR and 9 PR, that is a 62% res ponse rate. The first course resulted in 5 PR, 5 MR, SD, and 1 PD; aft er the subsequent course in all responding patients, response persiste d or improved whereas in no patient with SD any improvement was observ ed. The correlation of response to the first course with response to t he second course was statistically significant (P = 0.0009). The main toxicity of the single course was hematologic and consisted of rapidly reversible grade 3-4 neutropenia and thrombocytopenia in 94% of patie nts. Pharmacokinetic studies showed a very limited interpatient variab ility of both Cmax 57.6 +/- 9.9 mug/ml) and AUC (15.3 +/- 1.5 mg/ml . min) of free CBDCA, which eliminates an important variable in the eval uation of response. In conclusion, this ''in vivo test'' appears effec tive, reasonably safe, and reproducible in identifying patients likely to benefit from CBCDA: after a period of time as short as 3-4 weeks f ollowing the first course, multidrug chemotherapy including CBDCA may be employed in the responding patients, whereas an alternative regimen would be indicated in the non-responding patients. (C) 1995 Wiley-Lis s, Inc.