A neoadjuvant (preradiotherapy)
chemotherapy regimen consisting of either
cyclophosphamide alone (60 to 80 mg/kg) or a modified multidrug regimen (
vinblastine,
bleomycin,
cyclophosphamide, and
cisplatin) was administered to 15 newly diagnosed patients with histologically confirmed, fully staged, primary
germ-cell tumors (GCT's) of the central nervous system (CNS). There were 11 patients with
germinomas and four with non-
germinoma malignant GCT's. There were six females and nine males, whose median age was 13 years (range 4 months to 24 years). Seven
germinoma patients (64%) had disseminated disease. For the
germinoma patients, the subsequent
radiotherapy dose was modified based on the response to the
neoadjuvant chemotherapy, and craniospinal
radiotherapy was given only to those with disseminated
CNS disease at diagnosis. Ten of the 11
germinoma patients had complete disappearance of all evaluable disease after two courses of
chemotherapy (
cyclophosphamide in eight and multidrug in three) and one had a partial response. The planned dose of
radiotherapy to the primary
tumor was reduced from 5500 to 3000 rads, and the craniospinal dose was lowered from 3600 to 2000 rads. Ten patients remain in continuous disease-free remission 20+ to 89+ months after diagnosis (median follow-up period 47 months). All four patients with non-
germinoma GCT's received the multidrug regimen, and two fo three patients with evaluable disease had a partial response. High-dose regional and craniospinal
radiotherapy was administered thereafter, but only two patients remain in their first remission. Previously untreated
germinoma is a highly chemosensitive disease and the
neoadjuvant treatment strategy permits the identification of active
chemotherapy regimens in newly diagnosed patients. Patients who have complete responses to
neoadjuvant chemotherapy tolerate a significant
radiotherapy dose reduction without compromising long-term survival, thereby allowing a reduction of some of the late effects of therapeutic radiation.
Germinomas tend to disseminate early in the course of the disease and a pre-
therapy staging evaluation permits individualized
radiotherapy treatment planning.