RANDOMISED TRIAL OF ADJUVANT CHEMOTHERAPY WITH HIGH-DOSE DOXORUBICIN, IFOSFAMIDE AND LENOGRASTIM IN HIGH GRADE SOFT TISSUE SARCOMA
- Compare the local disease control, overall survival, and relapse-free survival in
patients with high-grade soft tissue sarcoma treated with adjuvant high-dose
doxorubicin and ifosfamide plus filgrastim (G-CSF) vs no adjuvant chemotherapy and
G-CSF after definitive surgery.
- Compare the toxicity and morbidity of these regimens in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
center, site of primary tumor (extremity vs trunk, including shoulder, pelvic girdle, head,
or neck vs central, including intrathoracic, visceral, uterine, or retroperitoneal), size of
primary tumor (less than 5 cm vs 5 cm or greater in largest diameter), postoperative
radiotherapy (yes vs no), and isolated limb perfusion therapy (yes vs no).
Some patients undergo isolated limb perfusion therapy with cytotoxics and/or cytokines.
No more than 8 weeks after biopsy or inadequate surgery, patients undergo definitive
surgery. Patients with complete resection undergo radiotherapy assessment and then
randomization. Patients with incomplete or marginal resection (except for central lesions)
undergo re-excision and, in the absence of macroscopic disease, assessment for postoperative
radiotherapy followed by randomization.
- Randomization: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive no adjuvant chemotherapy or filgrastim (G-CSF). Beginning
within 6 weeks after surgery, eligible patients undergo radiotherapy as outlined
- Arm II: Beginning within 4 weeks after surgery, patients receive high-dose
doxorubicin IV over 20 minutes followed by ifosfamide IV over 24 hours and G-CSF
subcutaneously daily beginning 24 hours after completion of ifosfamide infusion
and continuing for 10 days. Treatment continues every 3 weeks for 5 courses.
Beginning within 6 weeks after completion of chemotherapy, eligible patients
undergo radiotherapy as outlined below.
- Radiotherapy: Patients with incomplete or marginal resection undergo radiotherapy 5
days a week for 6-6.6 weeks. Patients with complete microscopic resection undergo
radiotherapy 5 days a week for 5 weeks followed by boost radiotherapy 5 days a week for
Patients are followed every 2 months for 1 year, every 3 months for 2 years, every 6 months
for 1 year, and then annually thereafter.
PROJECTED ACCRUAL: A total of 350 patients will be accrued for this study within 3.5 years.
Allocation: Randomized, Primary Purpose: Treatment
Penella J. Woll, MD, PhD
Cancer Research Centre at Weston Park Hospital
United States: Federal Government