Adult medulloblastoma: Multiagent chemotherapy

Abstract

In this study, the records of 17 adult patients with medulloblastoma treated with craniospinal radiation and 1 of 2 multiagent chemotherapy protocols were reviewed for progression-free survival, overall survival, and toxicity, and the patients were compared with each other and with similarly treated children and adults. Records of patients treated at 3 institutions were reviewed. Seventeen medulloblastoma patients (11 female, 6 male) with a median age of 23 years (range, 18-47 years) were treated with surgery, craniospinal radiation (CSRT) plus local boost, and 1 of 2 adjuvant chemotherapy regimens. All tumors were infratentorial (10 in 4th ventricle and 7 in left or right hemisphere). Ten patients presented with hydrocephalus, and 7 of them were shunted. Eight patients had gross total resection, 7 had subtotal resection (>50% removed), and 2 had partial resection (<50% removed). Postoperatively, 3 patients had positive cytology and 3 had positive spinal MRI. Five patients were classified as good risk and 12 were classified as poor risk (Chang staging system). Ten patients were treated with the "Packer protocol," consisting of CSRT plus weekly vincristine followed by 8 cycles of cisplatin, lomustine, and vincristine. Seven patients were treated with the Pediatric Oncology Group (POG) protocol, consisting of alternating courses of cisplatin/etoposide and cyclophosphamide/vincristine, followed by CSRT. Eight of 17 patients relapsed, with all 8 relapsing at the primary site. Other relapse sites included the leptomeninges (5), bone (1), and brain (1). The estimated median relapse-free survival (Kaplan-Meier) for all patients was 48 months (95% confidence interval, >26 months to infinity). Median relapse-free survival for patients on the Packer protocol was 26 months, and for those on the POG regimen was 48 months (P = 0.410). Five of 10 on the Packer protocol were relapse-free, while 4 of 7 were relapse-free on the POG regimen. Two patients relapsed during chemotherapy and 6 relapsed after completing all therapy at 18, 18, 26, 30, 40, and 48 months. The estimated median survival of all patients was 56 months (95% confidence interval, 27 to infinity) with 11 patients alive; for the Packer protocol, median survival was 36 months, and for the POG protocol, it was 57 months (P = 0.058). The hazard ratio was 0 (95% confidence interval, 0 to infinity). Toxicity during the Packer protocol was moderately severe, with only 1 of 10 patients able to complete all therapy. Two patients had severe abdominal pain during CSRT + vincristine, and 5 had peripheral neuropathy during vincristine therapy. Hearing loss (>20 dB) occurred in 7, neutropenia (<500 microl) in 6, thrombocytopenia (<50,000 microl) in 6, nephrotoxicity (>25% decrease by creatinine clearance) in 2, and decreased pulmonary function (diffusing capacity for carbon monoxide decrease >40%) in 1. On the POG protocol, only 1 patient had persistent nausea and vomiting, 2 had peripheral neuropathy, and 3 had hearing deficit (>20 dB) or tinnitus. The POG and Packer protocols...

Adjuvant chemotherapy in average-risk adult medulloblastoma patients improves survival: a long term study

“…Thus, data from retrospective studies including patients with homogeneous treatments and a long follow up period are essential to provide data. Furthermore, the patients experienced considerably greater chemotherapy-related toxicity than did children treated on an identical protocol (11). In a study by Friedrich et al adult patients were treated with lomustine, vincristine and cisplatin for 8 cycles after RT according to the HIT 2000 protocol.…”

Medulloblastoma

“…Medulloblastoma is much less common in adults, accounting for less than 1% -3% of primary CNS tumors [24,113,114]. The annual incidence of medulloblastoma is 1-1.5 cases per million in the general adult population and 80% occur before the end of the fourth decade [24,[113][114][115]. Treatment protocols are limited for adults and they are treated by heterogeneous ways using various chemo-radiotherapy regimens with surgery with post-operative CSI being the mainstay of treatment [115].…”

“…Adult medulloblastomas are clinically similar to that in the pediatric population, but lateral location and desmoplastic type is more frequent in adults as opposed to the pediatric age group. Adult medulloblastomas are thus, more amenable to complete resection and better outcome is expected because of their locations and histopathological variants respectively [24,[113][114][115][116]. Relapse following complete treatment is relatively late in adults as compared to children and they have a relatively prolonged time from relapse to death [116].…”