RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as G-CSF may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. It is not yet known whether chemotherapy and surgery plus G-CSF is more effective than chemotherapy and surgery alone in treating patients with osteosarcoma. PURPOSE: Randomized phase III trial to compare the effectiveness combination chemotherapy and surgery with or without G-CSF in treating patients who have newly diagnosed osteosarcoma.

Condition	Treatment or Intervention	Phase
localized osteosarcoma	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: surgery  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: conventional surgery  Drug: cisplatin  Drug: doxorubicin  Drug: filgrastim	Phase III

Further Study Details: 

OBJECTIVES: I. Determine the overall and disease-free survival of patients with newly diagnosed osteosarcoma of the extremity treated with conventional vs intensive cisplatin and doxorubicin with or without filgrastim (G-CSF) before and after definitive surgery. II. Compare the toxicity of these regimens in these patients. III. Compare the response in patients treated with these regimens.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive conventional doxorubicin (DOX) IV over 4 hours on days 1-3 and cisplatin (CDDP) IV continuously on day 1. Treatment continues every 3 weeks for 2 courses. At week 6, patients undergo amputation or local resection based on pretherapy imaging and response to chemotherapy. Beginning 2 weeks after surgery, patients receive 4 additional courses of conventional chemotherapy. Arm II: Patients receive intensive DOX and CDDP as above on day 1 plus filgrastim (G-CSF) subcutaneously on days 4-13. Treatment continues every 2 weeks for 3 courses. At week 6, patients undergo definitive surgery as in arm I. Beginning 2 weeks after surgery, patients receive 3 additional courses of intensive DOX and CDDP with G-CSF. Patients who experience disease progression during preoperative chemotherapy undergo surgery earlier than scheduled and complete all scheduled chemotherapy (6 courses) after surgery, at the discretion of the surgeon and oncologist. Within 4 weeks after limb-sparing procedure, patients with inadequate margins undergo amputation, followed 2 weeks later by chemotherapy. Patients are followed monthly for 6 months, every 2 months for 6 months, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 500 patients will be accrued for this study.

Ages Eligible for Study:  up to  40 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven resectable osteosarcoma of the long bone of an extremity
• No parosteal (juxtacortical), periosteal, Pagetoid, or post-irradiation sarcoma
• No distant metastases

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No other concurrent chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: See Disease Characteristics
• Surgery: See Disease Characteristics
• Other: No prior therapy

--Patient Characteristics--

• Age: 40 and under
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: Neutrophil count at least 1,500/mm3 OR WBC at least 3,500/mm3 Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.2 mg/dL
• Renal: Glomerular filtration rate at least 60 mL/min
• Cardiovascular: No history of cardiac dysfunction
• Other: No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix

Belgium
      Cliniques Universitaires Saint-Luc, Brussels (Bruxelles),  1200,  Belgium
      Institut Jules Bordet, Brussels (Bruxelles),  1000,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
Denmark
      Aarhus Kommunehospital, Aarhus,  DK-8000,  Denmark
      Rigshospitalet, Copenhagen,  2100,  Denmark
France
      Centre Eugene Marquis, Rennes,  35064,  France
Netherlands
      Academisch Ziekenhuis Utrecht, Utrecht,  3584 CX,  Netherlands
      Emma Kinderziekenhuis, Amsterdam,  NL-1100 DE,  Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands
      Onze Lieve Vrouwe Gasthuis, Amsterdam,  1091 HA,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands
Portugal
      Instituto Portugues de Oncologia de Francisco Gentil-Centro de Lisboa, Lisbon,  1099-023 Codex,  Portugal
Saudi Arabia
      King Faisal Specialist Hospital and Research Centre, Riyadh,  11211,  Saudi Arabia
Slovenia
      Institute of Oncology, Ljubljana, LJUBLJANA,  Sl-1000,  Slovenia
United Kingdom, England
      St. James's Hospital, Leeds,  England,  LS9 7TF,  United Kingdom

Study chairs or principal investigators

Marianne A. Nooij,  Study Chair,  European Osteosarcoma Intergroup   
Ian J. Lewis,  Study Chair

Study ID Numbers:  CDR0000078531; EOI-80931; EORTC-80931; EU-93024
Record last reviewed:  April 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002539
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08