Journal of Clinical Oncology, Vol 15, 2378-2384, Copyright © 1997 by American Society of Clinical Oncology
High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies--dose-response and schedule dependence
SR Patel, S Vadhan-Raj, N Papadopolous, C Plager, MA Burgess, C Hays and RS Benjamin
The Sarcoma Center, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. shreyaskumar_patel@mel_sarc.mda.uth.tmc.edu
PURPOSE: To evaluate the efficacy and feasibility of high-dose ifosfamide
(HDI) at a total dose of 14 g/m2 per cycle with mesna in combination with
granulocyte colony-stimulating factor (G-CSF) in adult patients with
sarcomas. PATIENTS AND METHODS: Between July 1991 and February 1994, 74
patients with sarcomas (37 bone and 37 soft tissue) were treated on two
simultaneous phase II studies that evaluated HDI given as a continuous
infusion over 74 hours. G-CSF was started on day 5 at 5 microg/kg/d until
recovery of granulocyte count. Additionally, between March 1993 and March
1994, 15 similar patients with previously treated bone or soft tissue
sarcomas were treated on a pilot study in which the same total dose of
ifosfamide was administered by a bolus schedule, along with mesna and
G-CSF. Patients were treated until maximal response, and where possible,
surgical resection of gross disease was performed. RESULTS: Seventy-two
patients from the phase II study using continuous infusion are assessable
for response. Four complete responses (CRs) and 17 partial responses (PRs)
were noted, for an overall response rate of 29% (95% confidence interval
[CI], 19% to 39%). The response rate was 40% (95% CI, 24% to 56%) for bone
sarcomas and 19% (95% CI, 6% to 32%) for soft tissue sarcomas. Fourteen
patients from the pilot study that used a bolus schedule are assessable for
response. One CR and seven PRs were noted, for an overall response rate of
57% (95% CI, 31% to 83%) and a response rate of 45% for soft tissue
sarcomas. Two patients developed grade 3 to 4 renal toxicity, three
developed grade 3 CNS toxicity, one had possible grade 3 cardiac toxicity,
and two developed severe painful peripheral neuropathy. There were no
treatment-related deaths. CONCLUSION: HDI at 14 g/m2 with mesna and G-CSF
is an active salvage regimen for patients with bone and soft tissue
sarcomas. There is a definite positive dose-response curve, and bolus
administration appears to be more active than continuous infusion.
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