Combination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Hyperthermia therapy kills tumor cells by heating them to several degrees above body temperature. It is not known whether receiving chemotherapy plus hyperthermia is more effective than receiving chemotherapy alone in treating patients with soft tissue sarcoma. PURPOSE: This randomized phase III trial is studying combination chemotherapy alone to see how well it works compared to combination chemotherapy and hyperthermia therapy in treating patients with soft tissue sarcoma.

Sex

All

Minimum age

18 Years

Maximum age

70 Years

DISEASE CHARACTERISTICS:

* 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

PATIENT CHARACTERISTICS:

Age:

* 18 to 70

Performance status:

* WHO 0-2 OR
* Karnofsky 60-100%

Life expectancy:

* Not specified

Hematopoietic:

* WBC at least 3,500/mm\^3
* Platelet count at least 100,000/mm\^3
* No bleeding disorder

Hepatic:

* Bilirubin less than 1.25 times upper limit of normal
* No severe hepatic dysfunction

Renal:

* Creatinine clearance greater than 60 mL/min
* No chronic renal failure

Cardiovascular:

* 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

Other:

* 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

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

Surgery:

* See Disease Characteristics
* No prior mutilative surgery

• BACKGROUNDStahl R, Wang T, Lindner LH, Abdel-Rahman S, Santl M, Reiser MF, Issels RD. Comparison of radiological and pathohistological response to neoadjuvant chemotherapy combined with regional hyperthermia (RHT) and study of response dependence on the applied thermal parameters in patients with soft tissue sarcomas (STS). Int J Hyperthermia. 2009 Jun;25(4):289-98. doi: 10.1080/02656730902873616. PMID 19670096
• RESULTIssels RD, Lindner LH, Verweij J, Wust P, Reichardt P, Schem BC, Abdel-Rahman S, Daugaard S, Salat C, Wendtner CM, Vujaskovic Z, Wessalowski R, Jauch KW, Durr HR, Ploner F, Baur-Melnyk A, Mansmann U, Hiddemann W, Blay JY, Hohenberger P; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC-STBSG); European Society for Hyperthermic Oncology (ESHO). Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010 Jun;11(6):561-70. doi: 10.1016/S1470-2045(10)70071-1. Epub 2010 Apr 29. PMID 20434400
• RESULTIssels RD, Lindner LH, Wust P, et al.: Regional hyperthermia (RHT) improves response and survival when combined with systemic chemotherapy in the management of locally advanced, high grade soft tissue sarcomas (STS) of the extremities, the body wall and the abdomen: a phase III randomised pros. [Abstract] J Clin Oncol 25 (Suppl 18): A-10009, 547s, 2007.
• RESULTLindner LH, Schlemmer M, Hohenberger P, et al.: Risk assessment of early progression among 213 pts with high-risk soft tissue sarcomas (HR-STS) treated with neoadjuvant chemotherapy regional hyperthermia: EORTC 62961/ESHO-RHT 95 intergroup phase III study. [Abstract] J Clin Oncol 23 (Suppl 16): A-9020, 821s, 2005.
• DERIVEDAlbertsmeier M, Milani V, Lindner LH, Tine G, Pasquali S, Callegaro D, Gronchi A, Durr HR, Klein A, Di Gioia D, Abdel-Rahman S, Schmidt M, Werner J, von Bergwelt-Baildon M, Miceli R, Issels R. Neoadjuvant chemotherapy for soft-tissue sarcoma of the extremities: A post-hoc Sarculator-based risk analysis of the EORTC 62961-ESHO 95 randomized trial. Cancer. 2026 May 1;132(9):e70427. doi: 10.1002/cncr.70427. PMID 42035475