Journal of Clinical Oncology, Vol 6, 44-50, Copyright © 1988 by American Society of Clinical Oncology
Very-high-dose cisplatin and etoposide in children with untreated advanced neuroblastoma
O Hartmann, CR Pinkerton, T Philip, JM Zucker and F Breatnach
Pediatric Department, Institut Gustave-Roussy, Villejuif, France.
Between January and December 1985, 17 children with advanced neuroblastoma
who were greater than 1 year old (16 stage IV, one stage III) were
administered cisplatin (CPDD, 200 mg/m2) and etoposide (VP- 16, 500 mg/m2)
as a pilot study of toxicity and response rates for the European
Neuroblastoma Study Group (ENSG). The study was designed to assess toxicity
of two courses of treatment, and evaluate response rates after this short
therapy. The creatinine clearance declined in seven of 15 patients. No
patient experienced clinically significant hearing loss, but formal
audiometric assessment of nine children revealed characteristic high tone
loss in seven patients. Peripheral neuropathy was not seen. Asymptomatic
hypomagnesemia (less than 0.7 microEq/L) was frequent, despite routine
supplementation. Asymptomatic electrolyte imbalances occurred frequently,
but were generally transient. Myelosuppression was severe, but brief. Seven
patients required platelet transfusions and seven were readmitted between
courses due to febrile episodes while neutropenic. There were no
treatment-related deaths. According to strictly defined criteria, 12 of 17
patients showed a partial response (PR), and extensive marrow evaluation
showed complete clearing of disease in six of 15 patients. This high-dose
regimen, if carefully supervised, is associated with acceptable toxicity,
comparable to that seen when the dose of CPDD is spread over several
months. The rapidity and degree of response was encouraging and merits
further evaluation.