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Clinical Therapy Trials - Other |
Departments of Neurology (H.S.G.) and Biostatistics (S.W.), University of Michigan, Ann Arbor, MI 48109; Department of Neurology, Kaiser-Permanente, Baldwin Park, CA 91706 (M.C.C.); Department of Neurology, Brown University, Providence, RI 02912 (M.J.G.)
1 Address correspondence and reprint requests to H.S. Greenberg, Department of Neurology, University of Michigan, 1914 Taubman Center, Box 0316, Ann Arbor, MI 48109.
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
). 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 ) 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
). 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 µl) in 6, thrombocytopenia (<50,000 µl) in 6,
nephrotoxicity (>25% 
by creatinine clearance) in 2, and
decreased pulmonary function (diffusing capacity for carbon monoxide
>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 did not have a
statistically significant difference in relapse-free or overall survival
because of the small sample size. The POG protocol seemed to have less
nonhematologic toxicity. Adults on the Packer protocol appeared to have
shorter median survival and greater toxicity than did children. To know
whether adding adjuvant chemotherapy to craniospinal radiation in adult
therapy increases relapse-free and overall survival, we must await the results
of a larger randomized controlled clinical trial.
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