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Randomized Study Comparing Neoadjuvant Chemotherapy Etoposide + Ifosfamide + Adriamycin (EIA) Combined With Regional Hyperthermia (RHT) Versus Neoadjuvant Chemotherapy Alone in the Treatment of High-Risk Soft Tissue Sarcomas in Adults

Phase 3
18 Years
70 Years
Open (Enrolling)

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Trial Information

Randomized Study Comparing Neoadjuvant Chemotherapy Etoposide + Ifosfamide + Adriamycin (EIA) Combined With Regional Hyperthermia (RHT) Versus Neoadjuvant Chemotherapy Alone in the Treatment of High-Risk Soft Tissue Sarcomas in Adults


- Determine local progression-free survival of patients with high-risk soft tissue
sarcoma treated with neoadjuvant etoposide, ifosfamide, and doxorubicin with or without
regional hyperthermia.

- Determine the tumor response rate, local disease control rate, and overall survival in
patients treated with this regimen.

OUTLINE: This is a randomized study. Patients are stratified according to high-risk category
(S1 vs S2 vs S3) and disease site (extremity vs nonextremity). Patients are randomized to
one of two treatment arms.

- Arm I: Patients receive etoposide IV over 30 minutes on days 1 and 4, ifosfamide IV
over 60 minutes on days 1-4, and doxorubicin IV over 30 minutes on day 1. Treatment
continues every 21 days for a total of 4 courses. Patients also undergo regional

- Arm II: Patients receive chemotherapy alone as in arm I. Patients in both arms undergo
definitive surgery 4-6 weeks after chemotherapy. Patients also undergo radiotherapy
beginning 4-6 weeks after surgery. After completion of surgery and radiotherapy,
patients with non-resectable tumors showing no disease progression receive an
additional 4 courses of chemotherapy with or without regional hyperthermia according to
above treatment schedule.

Patients are followed every 3 months for 1 year, every 4 months for 2 years, and then every
6 months thereafter.

PROJECTED ACCRUAL: A total of 340 patients (170 patients per arm) will be accrued for this
study within 3.5 years.

Inclusion Criteria


- Histologically proven grade II or III soft tissue sarcoma of one of following
high-risk groups:

- Grade II/III primary tumor with lesion size of at least 5 cm, deep, and
extracompartmental (S1)

- Local recurrence of primary tumor (S2)

- Inadequate surgical excision of S1 or S2 (S3)

- Disease recurrence after prior surgery allowed

- The following histological types are eligible:

- Malignant fibrous histiocytoma

- Liposarcoma (round cell and pleomorphic)

- Leiomyosarcoma

- Fibrosarcoma

- Rhabdomyosarcoma

- Synovial sarcoma

- Malignant paraganglioma

- Neurofibrosarcoma (malignant schwannoma)

- Extraskeletal Ewing's sarcoma

- Extraskeletal osteosarcoma

- Malignant peripheral neuroectodermal tumors

- Mesenchymal chondrosarcoma

- Angiosarcoma

- Miscellaneous sarcoma

- Unclassified sarcoma

- No distant metastases



- 18 to 70

Performance status:

- WHO 0-2 OR

- Karnofsky 60-100%

Life expectancy:

- Not specified


- WBC at least 3,500/mm^3

- Platelet count at least 100,000/mm^3

- No bleeding disorder


- Bilirubin less than 1.25 times upper limit of normal

- No severe hepatic dysfunction


- Creatinine clearance greater than 60 mL/min

- No chronic renal failure


- No documented existing cardiac failure

- No manifest heart failure (New York Heart Association class III or IV)

- Left ventricular ejection fraction no more than 10% below institutional normal


- No other prior or concurrent malignancy except adequately treated basal cell skin
cancer or carcinoma in situ of the cervix

- No other severe disease

- No severe cerebrovascular disease

- No extremely obese patients

- No prior metallic implants relevant to the regional hyperthermia field

- Not pregnant or nursing


Biologic therapy:

- Not specified


- No prior chemotherapy

Endocrine therapy:

- Not specified


- No prior radiotherapy (except to disease recurrence outside study irradiation field)


- See Disease Characteristics

- No prior mutilative surgery

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Local progression-free survival

Safety Issue:


Principal Investigator

Rolf D. Issels, MD, PhD

Investigator Affiliation:

Klinikum der Universitaet Muenchen - Grosshadern Campus


United States: Federal Government

Study ID:




Start Date:

July 1997

Completion Date:

Related Keywords:

  • Sarcoma
  • adult angiosarcoma
  • adult fibrosarcoma
  • adult leiomyosarcoma
  • adult liposarcoma
  • adult neurofibrosarcoma
  • adult synovial sarcoma
  • stage III adult soft tissue sarcoma
  • recurrent adult soft tissue sarcoma
  • adult extraskeletal osteosarcoma
  • adult malignant fibrous histiocytoma
  • adult rhabdomyosarcoma
  • stage I adult soft tissue sarcoma
  • stage II adult soft tissue sarcoma
  • Fever
  • Sarcoma