2002 CTOS Annual Meeting Oral Presentations — Pediatric Oncology

A RANDOMIZED TRIAL OF AMIFOSTINE WITH HIGH-DOSE ALKYLATOR THERAPY IN EWING SARCOMA: A CHILDREN'S ONCOLOGY GROUP TRIAL (P9457)
[Abstract ID: 37]

Category: Pediatric Oncology

Presentation: Oral

Authors: Mark L Bernstein¹, Meenakshi Devidas¹, Paul Meyers¹, Dominique Lafreniere¹, Allen Goorin¹, Holcombe Grier¹

Author Institutions: ¹Childrens Oncology Group, United States

Presenter: Mark L Bernstein
bernstm@magellan.umontreal.ca

Correspondent: Mark L Bernstein
bernstm@magellan.umontreal.ca
Montreal Quebec Canada H3T 1C5
Ph: 514-345-4969
Fax: 514-345-4792

Objectives: To determine if amifostine given twice with each dose
of ifosfamide or cyclophosphamide could provide protection
from the myelotoxic effects of high dosage alkylator
therapy, and prevent delay in the adminstration
of chemotherapy.

Methods: Patients (pts) less than 30 years of age with Ewing sarcoma metastatic at diagnosis and normal organ function were enrolled on a study of maximally intensified alkylator therapy without stem cell support.

Cycles included alternating courses of ifosfamide (3.6 g/m2/day,for 5 days, week 6, then 2.8 g/m2/day,for 5 days, weeks 12 and 18), with etoposide (100 mg/m2/day,for 5 days) and vincristine (2 mg/m2), doxorubicin (75 mg/m2 over 48 hours) and cyclophosphamide (2.1 g/m2/day, for 2 days, weeks 9 and 15). Seventy pts were randomized to receive (36 pts), or not to receive (34 pts) amifostine. Topotecan(0.75 mg/m2/day,for 5 days) and cyclophosphamide (250 mg/m2/day,for 5 days) were administered to 23 patients on the amifostine arm (weeks 0, 3)and 16 on the no amifostine arm. The amifostine dosage administered was 825 mg/m2 15 minutes prior to, and 3 hours after the beginning of each dose of ifosfamide or cyclophosphamide, with premedications and precautions as previously described. Days ANC < 500/ul, days platelets < 50,000/ul and days between cycles were analyzed at weeks 6, 12 and 18 of therapy.

Results: There was no significant difference seen in any of the parameters studied: the mean number of days with platelet count < 50,000/ul:
Wilcoxon rank sum test (WRS test, p-value: 0.29), the mean number of days with absolute neutrophil count < 500/ul: (WRS, p = 0.15), or the number of days until the next chemotherapy cycle: (p= 0.42).
Toxicities attributable to amifostine included increased emesis, reversible hypotension, and asymptomatic hypocalcemia responding to calcium supplementation.

Conclusions: In the dose and schedule used, amifostine did not provide
myeloprotection from the toxicity of high dose alkylator
therapy, and did not shorten the interval until the
administration of the next chemotherapy cycle.