Birmingham,
Alabama
35294
Purpose:
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor
cells. Combining radiation therapy with more than one chemotherapy drug may kill more tumor
cells.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus
radiation therapy followed by surgery in treating patients who have soft tissue sarcoma.
Study summary:
OBJECTIVES: I. Assess whether patients with high-grade soft tissue sarcoma (STS) treated
with neoadjuvant mesna/doxorubicin/ifosfamide/dacarbazine (MAID) plus radiotherapy in a
cooperative group setting exhibit a response rate, toxicity, and complication rate
comparable to those seen in pilot data collected by the Massachusetts General Hospital. II.
Assess local control and local complications related to surgery and neoadjuvant MAID plus
radiotherapy in these patients. III. Develop a tissue repository of frozen STS for ancillary
genetic and flow cytometric analysis of these tumors. IV. Form an Intergroup Working Sarcoma
Group that will develop a patient base, relationships, and support for the future
development and completion of a phase III study of adjuvant therapy for STS.
OUTLINE: The following acronyms are used: DOX Doxorubicin, NSC-123127 DTIC Dacarbazine,
NSC-45388 EBRT External-Beam Radiotherapy (equipment unspecified) G-CSF Filgrastim;
Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629 IFF Ifosfamide, NSC-109724 MAID
Mesna/DOX/IFF/DTIC Mesna Mercaptoethane sulfonate, NSC-113891 3-Drug Combination
Chemotherapy plus Radiotherapy followed by Surgery followed, if indicated, by Radiotherapy
followed by 3-Drug Combination Chemotherapy. MAID; plus EBRT to the primary tumor and
suspected microscopic disease; followed by minimal wide surgical excision; followed, if
positive margins, by postoperative EBRT; followed by MAID.
PROJECTED ACCRUAL: There will be 60 patients accrued into this study within 15 months.
Criteria:
DISEASE CHARACTERISTICS: Histologically confirmed soft tissue sarcoma of an extremity or
the body wall that is a primary or a postoperatively recurrent tumor Biopsy required
within 2 months prior to entry Grade II or III tumor, including AJCC stages IIB and IIIB
lesions at least 8 cm in diameter No more than 4 chest lesions that are no greater than 3
mm in diameter on preoperative CT The following histologies are excluded: Angiosarcoma of
the scalp or face Chondrosarcoma Extraosseous Ewing's sarcoma Head and neck sarcoma
Kaposi's sarcoma Osteosarcoma Primitive neuroectodermal tumor Rhabdomyosarcoma Patients on
this study are also eligible for Frozen Tumor Repository study (protocol RTOG-9308)
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 80%-100%
Hematopoietic: WBC at least 4,000/mm3 Platelet count at least 150,000/mm3 Hepatic:
Bilirubin no greater than 1.5 mg/dL SGOT no greater than 50 U Renal: Creatinine no greater
than 1.5 mg/dL Cardiovascular: No congestive heart failure (CHF) within 6 months No
myocardial infarction (MI) within 6 months No New York Heart Association class II-IV heart
disease Left ventricular ejection fraction at least 50% by MUGA or echocardiogram If
history of CHF or MI, criterion must be met within past 6 months Other: No
contraindication to surgery No uncontrolled bacterial, viral, or fungal infection No
serious medical or psychiatric illness that precludes informed consent or limits survival
to less than 2 years No second malignancy within 5 years except: Surgically treated in
situ cervical cancer Nonmelanomatous skin cancer Not pregnant or nursing Negative
pregnancy test required of fertile women within 7 days prior to entry Effective
contraception required of all fertile patients
PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy Chemotherapy: No
prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy
Surgery: See Disease Characteristics