Chemotherapy, Irradiation, and Surgery for Function-Preserving Curative Therapy of Primary Extremity Soft Tissue Sarcomas: Initial Treatment With I-MAP and GM-CSF; Aerosol GM-CSF During Preoperative Irradiation and Postoperatively
- To evaluate 2-year pulmonary metastatic progression rates in patients with primary
high-grade extremity soft tissue sarcoma who have received preoperative I-MAP, plus
aerosol GM-CSF, plus irradiation with concomitant MAP followed by post-operative
- To evaluate survival of these patients.
- To evaluate time to progression in these patients.
- To evaluate toxicity in these patients.
- To evaluate tumor response in these patients.
- To observe and describe sequentially before treatment, after treatment, and after
recovery from treatment the frequency of skin test anergy and cellular immunity in
extremity soft tissue sarcoma receiving systemic GM-CSF preoperatively and aerosol
GM-CSF as part of both preoperative and postoperative treatment.
- Neoadjuvant treatment: Patients receive ifosfamide IV over 2 hours on days 0 and 1 and
cisplatin IV over 4 hours, mitomycin IV and doxorubicin IV on day 1. Treatment repeats
every 28 days for 2 courses in the absence of disease progression or unacceptable
toxicity. Patients also receive sargramostim (GM-CSF) subcutaneously (SC) every 12
hours on days -6 to -3, 2-14, and 22-25. Beginning on day 84 patients also undergo
radiotherapy once daily, five days a week, continuing for five weeks. Patients also
receive GM-CSF SC twice daily on days -3 and 2 -15 and aerosol GM-CSF twice daily on
days 85 - 91, 99 -105, and 113 - 119.
- Chemoradiotherapy: Beginning 4 weeks after completion of neoadjuvant chemotherapy,
patients undergo radiotherapy (RT) once daily, 5 days a week, for 5 weeks. Patients
also receive aerosolized GM-CSF twice daily on days 2-8, 16-22, and 30-38 and mitomycin
C IV, doxorubicin hydrochloride IV, and cisplatin IV over 2 hours on days 1 and 29.
- Surgery: Four weeks after completion of chemotherapy, patients undergo surgery.
Patients may also undergo intraoperative RT electron boost or intraoperative high-dose
- Adjuvant treatment: Beginning 4 weeks after surgery, patients receive aerosol GM-CSF
twice daily on days -7, 15-21, 35-42, 56-63, and 77-84. Some patients may undergo
external beam RT 2-4 weeks after surgery.
Blood samples are collected at baseline and at 4 and 14 weeks after surgery. Samples are
tested for NY-ESO-1 by staining, for T-cell subset by flow cytometry, and for autologous
lymphocyte proliferation. Patients may also be tested for delayed-type hypersensitivity and
skin test anergy.
After completion of study therapy, patients are followed every 3 months for 1 year, every 4
months for 1 year, every 6 months for 2 years, and at 5 years.
Masking: Open Label, Primary Purpose: Treatment
Pulmonary metastatic progression-free rate at 2 years
Scott Okuno, MD
United States: Food and Drug Administration