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Toxicities associated with
chemotherapy followed by craniospinal radiation for adults with poor-risk
medulloblastoma/PNET and disseminated ependymoma; a preliminary report of ECOG
4397
P. L. Moots, A. O'Neill, G. R. Barger, M. P. Mehta, M. R. Gilbert
Vanderbilt University, Nashville, TN; Dana Farber Cancer
Institute, Boston, MA; Karmanos Cancer Institute, Wayne State University,
Detroit, MI; University of Wisconsin, Madison, WI; M. D. Anderson Cancer Center,
Houston, TX
Background.
The treatment of poor-risk medulloblastoma (MED) in adults
derives from results in children indicating improved survival with combined
modality therapy.
In adults, chemotherapy is limited by hematological toxicities when given after
craniospinal radiation.
ECOG 4397 is designed to assess the toxicities, response rate, and long-term
control in poor-risk patients treated with multi-agent chemotherapy prior to
craniospinal radiation.
This trial represents the collaborative efforts of ECOG and SWOG
participants.
Methods.
Patients greater than 18 years with: 1) poor-risk MED/PNET, or
2) ependymoma with subarachnoid metastases were treated with three cycles of
cisplatin (70 mg/m2, day 1), cyclophosphamide (700 mg/m2/d, day 2-3), etoposide
(70 mg/m2, days 1-3), and vincristine (1.5 mg/m2 up to 2 mg, days 1 and 14)
every 4 weeks.
G-CSF was used.
Radiation included 36 Gy to the craniospinal axis followed by a boost to 54 Gy
to the primary site.
MRI scans were performed after each cycle to monitor response.
Results.
Toxicity data is shown for the first ten patients (8 MED, 1
PNET, 1 ependymoma).
Median age is 34 years.
Nine of 10 patients received three cycles of chemotherapy.
Hematological toxicity predominated with grade 3/4 neutropenia in 6 cycles, and
grade 3/4 thrombocytopenia in 4 cycles.
Nausea worse than grade 1 was observed in 3 cycles.
Other grade 3/4 toxicities included fatigue (1), anorexia (1), dehydration (2),
agitation (1), neuropathy (1), hypokalemia (1), hyponatremia (2), and elevated
creatinine (1).
One patient experienced tumor progression after cycle 2.
One patient died of pulmonary emboli after cycle 3.
All nine patients who began radiation completed the planned course.
Conclusions.
This chemotherapy regimen, derived from pediatric
experience, can be administered in adults with acceptable toxicities for three
cycles.
Chemotherapy did not interfere with completion of craniospinal radiation.
Response data has not been analyzed because the trial is ongoing, but
radiographic progression prior to completing chemotherapy occurred only once.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-001474,00.asp
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