Combination Chemotherapy, Radiation Therapy, and Sargramostim Before and After Surgery in Treating Patients With Soft Tissue Sarcoma That Can Be Removed By Surgery

OBJECTIVES:

Primary

• 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 aerosol GM-CSF.

Secondary

• 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.

Translational

• 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.

OUTLINE:

• 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 brachytherapy.
• 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.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary soft tissue sarcoma

• Sarcoma must be of the extremity or limb girdle origin
• No metastatic disease
• High-grade
• Must be a candidate for preoperative irradiation for potential limb-sparing surgery
• Must not have any of the following:

• Embryonal rhabdomyosarcoma
• Extraosseous Ewing sarcomas

PATIENT CHARACTERISTICS:

Inclusion criteria

• ECOG performance status 0 - 2
• WBC ≥ 3,500/μL OR granulocyte count ≥1,500/μL
• Platelets ≥150,000/μL
• Direct-reacting bilirubin ≤ 0.3 mg/dL
• Creatinine ≤1.2 times the upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Exclusion criteria

• Significant infection
• Active heart disease including any of the following:

• Myocardial infarction in the past 3 months
• Symptomatic coronary artery insufficiency
• First-degree heart block
• Clinical history of congestive heart failure
• Symptomatic pulmonary disease.

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy for cancer