Intensive Multi-Agent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide (IE) and Vincristine/Doxorubicin/Cyclophosphamide (VDC) for Patients With High-Risk Rhabdomyosarcoma
Intensive Multi-Agent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide (IE) and Vincristine/Doxorubicin/Cyclophosphamide (VDC) for Patients With High-Risk Rhabdomyosarcoma
RATIONALE: Drugs used in chemotherapy, such as vincristine, irinotecan, ifosfamide, etoposide, doxorubicin, cyclophosphamide, and dactinomycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving high-dose combination chemotherapy together with radiation therapy may kill more tumor cells.
PURPOSE: This phase III trial is studying how well giving high-dose combination chemotherapy together with radiation therapy works in treating patients with newly diagnosed metastatic rhabdomyosarcoma or ectomesenchymoma.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a prospective, nonrandomized, multicenter study. Patients are stratified according to prognostic factors predictive of outcome (e.g. histology, bone/bone marrow involvement, and number of metastatic sites).
Patients receive high-dose chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; and ifosfamide IV over 1 hour and etoposide IV over 30-60 minutes on days 1-5 of weeks 9, 13, 17, 26, and 30. Patients also receive doxorubicin hydrochloride IV continuously over 24 hours on days 1 and 2 of weeks 7*, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; and dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44 in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously in weeks 7-9, 11-13, 15-17, 22, 26, 28-30, 32, 33, 35, 38, and 41-44 beginning 24-36 hours after the last chemotherapy dose and continuing until blood counts recover.
NOTE: *Patients undergoing early radiotherapy for intracranial extension do not receive doxorubicin in week 7.
Beginning at week 20 (or week 1 for patients with parameningeal tumors with intracranial extension [or spinal cord compression] requiring emergency radiotherapy), patients also undergo radiotherapy once a day, 5 days a week, for approximately 5½ weeks. Some patients may also undergo second-look surgery.
After completion of study treatment, patients are followed periodically for ≥ 10 years.
PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.
DISEASE CHARACTERISTICS:
Histologically confirmed high-risk rhabdomyosarcoma or ectomesenchymoma
Prior enrollment on COG-D9902 to confirm local histological diagnosis required
Newly diagnosed disease
Metastatic disease (stage IV, clinical group IV)
Has undergone initial surgical procedure (including biopsy) that provided the definitive diagnosis within the past 42 days
Parameningeal and paraspinal tumors allowed
Patients with evidence of ICE, as defined by contrast MRI showing that primary tumor touches, displaces, invades, distorts, or otherwise causes a signal abnormality of the dura in contiguity to the primary site in brain or spinal cord, are eligible
Patients requiring emergency radiotherapy are eligible
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
Birmingham, Alabama 35294, United States
Tucson, Arizona 85724-5024, United States
Little Rock, Arkansas 72205, United States
Loma Linda, California 92354, United States
Long Beach, California 90801, United States
Farmington, Connecticut 06360-2875, United States
Washington D.C., District of Columbia 20007, United States
Orlando, Florida 32803-1273, United States
Savannah, Georgia 31403-3089, United States
Indianapolis, Indiana 46202-5289, United States
Kansas City, Kansas 66160-7357, United States
Lexington, Kentucky 40536-0093, United States
Baltimore, Maryland 21231-2410, United States
Boston, Massachusetts 02111, United States
Boston, Massachusetts 02115, United States
Ann Arbor, Michigan 48109-0286, United States
Minneapolis, Minnesota 55404, United States
St Louis, Missouri 63110, United States
Omaha, Nebraska 68198-6805, United States
Lebanon, New Hampshire 03756-0002, United States
New Brunswick, New Jersey 08903, United States
New York, New York 10032, United States
Rochester, New York 14642, United States
Chapel Hill, North Carolina 27599-7295, United States
Charlotte, North Carolina 28232-2861, United States
Charlotte, North Carolina 28233-3549, United States
Winston-Salem, North Carolina 27157-1096, United States
Hershey, Pennsylvania 17033-0850, United States
Charleston, South Carolina 29425, United States
Sioux Falls, South Dakota 57117-5039, United States
Amarillo, Texas 79106, United States
Dallas, Texas 75390, United States
Burlington, Vermont 05401, United States
Roanoke, Virginia 24029, United States
Spokane, Washington 99220-2555, United States
Charleston, West Virginia 25302, United States
Westmead, New South Wales 2145, Australia
Herston, Brisbane, Queensland 4029, Australia
St. John's, Newfoundland and Labrador A1B 3V6, Canada