RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
they stop growing or die. Combining more than one drug may kill more tumor cells.
Chemoprotective drugs such as dexrazoxane may protect normal cells from the side effects of
chemotherapy.
PURPOSE: Phase III trial to study the effectiveness of three combination chemotherapy
regimens plus dexrazoxane in treating patients who have newly diagnosed nonmetastatic
osteosarcoma.
OUTLINE: This is a multicenter study. Patients are enrolled sequentially on 1 of 3 pilot
intensification regimens. After surgery to completely remove the primary tumor, patients are
assigned to 1 of 2 adjuvant chemotherapy groups based on percent necrosis at limb salvage.
Pilot 1: (Closed to accrual as of 6/2/2000) Patients receive dexrazoxane IV followed
immediately by doxorubicin IV over 20 minutes plus cisplatin IV over 4 hours on days 1 and 2
of weeks 1 and 6. Methotrexate IV over 4 hours is administered on day 1 of weeks 4, 5, 9, and
10. Patients undergo surgery on week 11. Adjuvant chemotherapy begins on day 1 of week 13.
Group 1 (good response to neoadjuvant chemotherapy): Patients receive methotrexate IV over 4
hours every 3 weeks for 6 courses, beginning on week 13. Patients also receive dexrazoxane
and doxorubicin every 3 weeks for 4 courses, beginning on week 14. Cisplatin is administered
with the first 2 courses of dexrazoxane and doxorubicin. Group 2 (standard response to
neoadjuvant chemotherapy): Patients receive methotrexate and cisplatin as in group 1 plus
dexrazoxane and doxorubicin for 6 courses. Pilot 2: Patients receive preoperative therapy
comprised of dexrazoxane, doxorubicin, and methotrexate as in pilot 1. Ifosfamide IV over 4
hours is also administered on days 1-5 of week 1. Patients undergo surgery on week 11, then
begin adjuvant chemotherapy on week 13. Group 1: Patients receive methotrexate, dexrazoxane,
and doxorubicin as in pilot 1, group 1. Ifosfamide is also administered on weeks 14 and 20.
Cisplatin is administered on weeks 17, 23, and 26. Group 2: Patients receive methotrexate,
dexrazoxane, and doxorubicin as in pilot 1, group 2. Ifosfamide is administered on weeks 14,
20, 26, and 31. Cisplatin is administered on weeks 17, 23, and 29. Pilot 3: (Open to accrual
as of 6/2/2000) Patients receive preoperative therapy comprised of methotrexate, dexrazoxane,
doxorubicin, ifosfamide, and cisplatin as in pilot 2. Patients undergo surgery on week 11,
then begin adjuvant chemotherapy on week 13. Group 1: Patients receive methotrexate,
dexrazoxane, doxorubicin, ifosfamide, and cisplatin as in pilot 2, group 1. Group 2: Patients
receive methotrexate on weeks 13, 19, 29, 32, 35, and 36, high dose ifosfamide and etoposide
IV over 4 hours on days 1-5 of weeks 14, 23, and 26, and cisplatin on weeks 20, 30, and 33.
Dexrazoxane and doxorubicin are administered on weeks 17, 20, 30, and 33. Patients are
followed every 3 months for 1 year, every 6 months for 4 years and then annually thereafter.
PROJECTED ACCRUAL: Approximately 180 patients will be accrued for this study within 2 years.
Academisch Ziekenhuis Groningen, Groningen 9713 EZ, Netherlands
San Jorge Childrens Hospital, Santurce 00912, Puerto Rico
Clinique de Pediatrie, Geneva 1211, Switzerland
Swiss Pediatric Oncology Group Bern, Bern CH 3010, Switzerland
MBCCOP - Gulf Coast, Mobile, Alabama 36688, United States
University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama 35294-3300, United States
Alberta Children's Hospital, Calgary, Alberta T2T 5C7, Canada
Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada
Arizona Cancer Center, Tucson, Arizona 85724, United States
University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States
British Columbia Children's Hospital, Vancouver, British Columbia V6H 3V4, Canada
Children's Hospital and Health Center, San Diego, California 92123-4282, United States
Children's Hospital Los Angeles, Los Angeles, California 90027-0700, United States
Children's Hospital of Orange County, Orange, California 92868, United States
David Grant Medical Center, Travis Air Force Base, California 94535, United States
Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095-1781, United States
Kaiser Permanente Medical Center - Santa Clara, Santa Clara, California 95051-5386, United States
Kaiser Permanente-Southern California Permanente Medical Group, San Diego, California 92120, United States
Long Beach Memorial Medical Center, Long Beach, California 90806, United States
Lucile Packard Children's Hospital at Stanford, Palo Alto, California 94304, United States
Sutter Cancer Center, Sacramento, California 95816, United States
UCSF Cancer Center and Cancer Research Institute, San Francisco, California 94143-0128, United States
University of California Davis Medical Center, Sacramento, California 95817, United States
University of California San Diego Cancer Center, La Jolla, California 92093-0658, United States
Children's Hospital of Denver, Denver, Colorado 80218, United States
Yale Comprehensive Cancer Center, New Haven, Connecticut 06520-8028, United States
Children's National Medical Center, Washington, District of Columbia 20010-2970, United States
Walter Reed Army Medical Center, Washington, District of Columbia 20307-5000, United States
All Children's Hospital, St. Petersburg, Florida 33701, United States
Baptist Hospital of Miami, Miami, Florida 33176-2197, United States
CCOP - Florida Pediatric, Tampa, Florida 33682-7757, United States
Miami Children's Hospital, Miami, Florida 33155, United States
Nemours Children's Clinic, Jacksonville, Florida 32207, United States
Shands Hospital and Clinics, University of Florida, Gainesville, Florida 32610-100277, United States
St. Mary's Hospital, West Palm Beach, Florida 33407, United States
Sylvester Cancer Center, University of Miami, Miami, Florida 33136, United States
Walt Disney Memorial Cancer Institute, Orlando, Florida 32803, United States
Emory University Hospital - Atlanta, Atlanta, Georgia 30322, United States
Cancer Research Center of Hawaii, Honolulu, Hawaii 96813, United States
Tripler Army Medical Center, Honolulu, Hawaii 96859-5000, United States
CCOP - Illinois Oncology Research Association, Peoria, Illinois 61602, United States
Children's Memorial Hospital, Chicago, Chicago, Illinois 60614, United States
Hope Children's Hospital, Oak Lawn, Illinois 60453, United States
Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, United States
Saint Jude Midwest Affiliate, Peoria, Illinois 61637, United States
University of Chicago Cancer Research Center, Chicago, Illinois 60637-1470, United States
Indiana University Cancer Center, Indianapolis, Indiana 46202-5289, United States
Holden Comprehensive Cancer Center at The University of Iowa, Iowa City, Iowa 52242-1009, United States
CCOP - Wichita, Wichita, Kansas 67214-3882, United States
University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States
Via Christi Regional Medical Center, Wichita, Kansas 67214, United States
CCOP - Ochsner, New Orleans, Louisiana 70121, United States
MBCCOP - LSU Health Sciences Center, New Orleans, Louisiana 70112, United States
Tulane University School of Medicine, New Orleans, Louisiana 70112, United States
Eastern Maine Medical Center, Bangor, Maine 04401, United States
Maine Children's Cancer Program, Portland, Maine 04101, United States
Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland 21201, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States
Boston Floating Hospital Infants and Children, Boston, Massachusetts 02111, United States
Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States
Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, United States
University of Massachusetts Memorial Medical Center, Worcester, Massachusetts 01655, United States
CCOP - Kalamazoo, Kalamazoo, Michigan 49007-3731, United States
Children's Hospital of Michigan, Detroit, Michigan 48201, United States
Hurley Medical Center, Flint, Michigan 48503, United States
St. John's Hospital and Medical Center, Detroit, Michigan 48236, United States
University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0752, United States
Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States
University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, United States
Keesler Medical Center - Keesler AFB, Keesler AFB, Mississippi 39534-2576, United States
University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States
Cardinal Glennon Children's Hospital, Saint Louis, Missouri 63104, United States
Children's Mercy Hospital, Kansas City, Missouri 64108, United States
University of Missouri-Columbia Hospital and Clinics, Columbia, Missouri 65212, United States
Washington University School of Medicine, Saint Louis, Missouri 63110, United States
University of Nebraska Medical Center, Omaha, Nebraska 68198-3330, United States
Norris Cotton Cancer Center, Lebanon, New Hampshire 03756-0002, United States
Cancer Institute of New Jersey, New Brunswick, New Jersey 08901, United States
CCOP - Northern New Jersey, Hackensack, New Jersey 07601, United States
Hackensack University Medical Center, Hackensack, New Jersey 07601, United States
University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, United States
Herbert Irving Comprehensive Cancer Center, New York, New York 10032, United States
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States
Mount Sinai School of Medicine, New York, New York 10029, United States
NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York, New York 10016, United States
Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States
Schneider Children's Hospital, New Hyde Park, New York 11042, United States
State University of New York - Upstate Medical University, Syracuse, New York 13210, United States
State University of New York Health Sciences Center - Stony Brook, Stony Brook, New York 11790-7775, United States
University of Rochester Cancer Center, Rochester, New York 14642, United States
Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States
Comprehensive Cancer Center at Wake Forest University, Winston-Salem, North Carolina 27157-1082, United States
Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States
East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, United States
Lineberger Comprehensive Cancer Center, UNC, Chapel Hill, North Carolina 27599-7295, United States
Mission Saint Joseph's Health System, Asheville, North Carolina 28801, United States
Presbyterian Healthcare, Charlotte, North Carolina 28233-3549, United States
CCOP - Merit Care Hospital, Fargo, North Dakota 58122, United States
Veterans Affairs Medical Center - Fargo, Fargo, North Dakota 58102, United States
IWK Health Centre, Halifax, Nova Scotia B3J 3G9, Canada
Children's Hospital Medical Center - Cincinnati, Cincinnati, Ohio 45229-3039, United States
Children's Hospital of Columbus, Columbus, Ohio 43205-2696, United States
Ireland Cancer Center, Cleveland, Ohio 44106-5065, United States
Natalie Warren Bryant Cancer Center, Tulsa, Oklahoma 74136, United States
Oklahoma Memorial Hospital, Oklahoma City, Oklahoma 73126-0307, United States
Children's Hospital, Hamilton, Ontario L8N 3Z5, Canada
Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
CCOP - Columbia River Program, Portland, Oregon 97213, United States
Doernbecher Children's Hospital, Portland, Oregon 97201-3098, United States
Legacy Emanuel Hospital and Health Center, Portland, Oregon 97227, United States
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134-1095, United States
Centre Hospitalier de L'Universite Laval, Sainte Foy, Quebec GIV 4G2, Canada
Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada
McGill University Health Center - Montreal Children's Hospital, Montreal, Quebec H3H 1P3, Canada
Children's Hospital of Greenville Hospital System, Greenville, South Carolina 29605, United States
Medical University of South Carolina, Charleston, South Carolina 29425-0721, United States
James H. Quillen College of Medicine, Johnson City, Tennessee 37614-0622, United States
Saint Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, United States
Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-6838, United States
Baylor College of Medicine, Houston, Texas 77030, United States
MBCCOP - South Texas Pediatric, San Antonio, Texas 78229-3900, United States
Medical City Dallas Hospital, Dallas, Texas 75230, United States
San Antonio Military Pediatric Cancer and Blood Disorders Center, Lackland Air Force Base, Texas 78236-5300, United States
Scott and White Clinic, Temple, Texas 76508, United States
Simmons Cancer Center - Dallas, Dallas, Texas 75235-9154, United States
Texas Oncology P.A., Dallas, Texas 75230-2503, United States
University of Texas - MD Anderson Cancer Center, Houston, Texas 77030-4009, United States
University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7811, United States
University of Texas Medical Branch, Galveston, Texas 77555-0209, United States
Vermont Cancer Center, Burlington, Vermont 05401-3498, United States
Royal Children's Hospital, Parkville, Victoria 3052, Australia
Cancer Center at the University of Virginia, Charlottesville, Virginia 22908, United States
Carilion Roanoke Community Hospital, Roanoke, Virginia 24029, United States
Inova Fairfax Hospital, Falls Church, Virginia 22042-3300, United States
Massey Cancer Center, Richmond, Virginia 23298-0037, United States
Naval Medical Center, Portsmouth, Portsmouth, Virginia 23708-2197, United States
Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, United States
Madigan Army Medical Center, Tacoma, Washington 98431-5000, United States
West Virginia University Hospitals, Morgantown, West Virginia 26506-9300, United States
West Virginia University Medical School-Charleston, Charleston, West Virginia 25304, United States
Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia
Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States
St. Vincent Hospital, Green Bay, Wisconsin 54307-3508, United States
University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792-6164, United States
