Combination Chemotherapy and Surgery With or Without G-CSF in Treating Patients With Osteosarcoma

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase: Completed; Phase 3

Conditions: Sarcoma

Treatments: Biological: filgrastim; Procedure: conventional surgery; Drug: doxorubicin hydrochloride; Drug: cisplatin

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT00002539

MRC-BO06

EORTC-80931

EOI-80931

EU-93024

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

• 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.
• Compare the toxicity of these regimens in these patients.
• Compare the response in patients treated with these regimens.

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.

Enrollment: 214 patients

Sex: All

Ages: Under 40 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

PATIENT CHARACTERISTICS:

Age:

• 40 and under

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Neutrophil count at least 1,500/mm^3 OR
• WBC at least 3,500/mm^3
• Platelet count at least 100,000/mm^3

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

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