15 research outputs found
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
response to CBDCA in the single patient. Exploration of CBDCA activity
was focused on response after the first course as compared to the
response 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
weeks later. After two cycles we observed 1 CR and 9 PR, that is a 62\%
response rate. The first course resulted in 5 PR, 5 MR, SD, and 1 PD;
after the subsequent course in all responding patients, response
persisted or improved whereas in no patient with SD any improvement was
observed. The correlation of response to the first course with response
to the 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
patients. Pharmacokinetic studies showed a very limited interpatient
variability 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 evaluation of response. In conclusion, this `'in vivo test'' appears
effective, reasonably safe, and reproducible in identifying patients
likely to benefit from CBCDA: after a period of time as short as 3-4
weeks following 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-Liss, Inc