RATIONALE: Drugs used in chemotherapy work in 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 amifostine may protect normal cells from the side effects of chemotherapy. It is not yet known which chemotherapy regimen is most effective for children and young adults with liver cancer.
PURPOSE: This randomized phase III trial is studying giving combination chemotherapy together with amifostine to see how well it works compared to combination chemotherapy alone in treating patients with liver cancer.
* Determine the event-free survival rate in children with stage III or IV unresectable or metastatic hepatoblastoma treated with cisplatin, vincristine, and fluorouracil (stages III and IV closed to accrual as of 11-25-03).
* Evaluate the efficacy of amifostine* in reducing toxicity associated with platinum agents in patients with hepatoblastoma.
* Determine whether amifostine* effects event-free survival in these patients in response to these regimens.
* Evaluate the event-free survival in patients with stage I pure fetal histology treated with surgery alone.
* Evaluate the efficacy of amifostine* in reducing toxicity associated with cisplatin in patients with resected tumors.
* Determine the response in patients treated with amifostine* in combination with these regimens.
NOTE: * Arm II (amifostine) closed to accrual as of 11-25-03; arm IV (amifostine) closed to accrual as of 4-5-02
OUTLINE: This is a randomized study. Patients are stratified according to disease stage (stage I pure fetal histology vs stage I other histology or stage II [stage II closed to accrual as of 11-25-03] vs stage III or IV [stages III and IV closed to accrual as of 11-25-03]). Patients are randomized to one of four treatment arms. (Arms III and IV closed to accrual as of 4-5-02) (Arm II closed to accrual as of 11-25-03)
All patients undergo surgical resection or attempted resection of tumor. Patients with pure fetal histology achieving complete tumor resection receive no further treatment. All other patients receive postoperative chemotherapy.
* Arm I: Patients receive cisplatin IV over 4 hours on day 1, vincristine IV on days 3, 10, and 17, and fluorouracil on day 3.
* Arm II (closed to accrual as of 11-25-03): Patients receive treatment as in arm I with the addition of amifostine IV over 15 minutes prior to cisplatin on day 1.
* Arm III (closed to accrual as of 4-5-02): Patients receive carboplatin IV over 1 hour on day 1 and cisplatin IV over 4 hours on day 15.
* Arm IV (closed to accrual as of 4-5-02): Patients receive treatment as in arm III with the addition of amifostine IV over 15 minutes prior to carboplatin on day 1.
Treatment repeats every 3 weeks for 4 courses in arms I and II (arm II closed to accrual as of 11-25-03) and every 4 weeks for 4 courses in arms III and IV (arms III and IV closed to accrual as of 4-5-02) in the absence of disease progression or unacceptable toxicity. Patients with stage III or IV disease (stages III and IV closed to accrual as of 11-25-03) undergo second look surgery and receive 2 additional courses of chemotherapy if achieving complete response after surgery.
Patients are followed monthly for 6 months, every 2 months for 2 years, every 3 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 356 patients will be accrued for this study within 5. 5 years.
University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama 35294, United States
University of South Alabama Mitchell Cancer Institute, Mobile, Alabama 36604, United States
Alberta Children's Hospital, Calgary, Alberta T3B 6A8, Canada
University of Alberta Hospital, Edmonton, Alberta T6G 1Z2, Canada
Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson, Arizona 85724-5024, United States
Phoenix Children's Hospital, Phoenix, Arizona 85016-7710, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States
Children's & Women's Hospital of British Columbia, Vancouver, British Columbia V6H 3V4, Canada
Children's Hospital and Research Center - Oakland, Oakland, California 94609-1809, United States
Children's Hospital Central California, Madera, California 93638-8762, United States
Childrens Hospital Los Angeles, Los Angeles, California 90027, United States
Children's Hospital of Orange County, Orange, California 92868, United States
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital, Long Beach, California 90801, United States
Kaiser Permanente Medical Center - Oakland, Sacramento, California 95825, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center, Loma Linda, California 92354, United States
Southern California Permanente Medical Group, Downey, California 90242-2814, United States
Stanford Comprehensive Cancer Center at Stanford University Medical Center, Stanford, California 94305, United States
Sutter Cancer Center, Sacramento, California 95816, United States
UCSF Comprehensive Cancer Center, San Francisco, California 94115, United States
University of California Davis Cancer Center, Sacramento, California 95817, United States
Children's Hospital Cancer Center, Denver, Colorado 80218-1088, United States
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center, Farmington, Connecticut 06360-2875, United States
Yale Cancer Center, New Haven, Connecticut 06520-8028, United States
Alfred I. duPont Hospital for Children, Wilmington, Delaware 19899, United States
Children's National Medical Center, Washington, District of Columbia 20010-2970, United States
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, District of Columbia 20007, United States
All Children's Hospital, St. Petersburg, Florida 33701, United States
Baptist-South Miami Regional Cancer Program, Miami, Florida 33176, United States
Broward General Medical Center Cancer Center, Ft. Lauderdale, Florida 33316, United States
Florida Hospital Cancer Institute at Florida Hospital Orlando, Orlando, Florida 32803-1273, United States
Lee Cancer Care of Lee Memorial Health System, Fort Myers, Florida 33901, United States
Memorial Cancer Institute at Memorial Regional Hospital, Hollywood, Florida 33021, United States
Miami Children's Hospital, Miami, Florida 33155, United States
Nemours Children's Clinic - Orlando, Orlando, Florida 32806, United States
Nemours Children's Clinic, Jacksonville, Florida 32207, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital, Tampa, Florida 33607, United States
University of Florida Shands Cancer Center, Gainesville, Florida 32610-0232, United States
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah, Georgia 31403-3089, United States
Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, United States
University Medical Center Groningen, Groningen 9713 EZ, Netherlands
San Jorge Children's Hospital, Santurce 00912, Puerto Rico
St. Luke's Mountain States Tumor Institute - Boise, Boise, Idaho 83712-6297, United States
Advocate Christ Medical Center, Oak Lawn, Illinois 60453, United States
Cancer Care Center at Advocate Lutheran Hospital, Park Ridge, Illinois 60068-1174, United States
Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States
Southern Illinois University School of Medicine, Springfield, Illinois 62794-9620, United States
University of Chicago Cancer Research Center, Chicago, Illinois 60637-1470, United States
Indiana University Cancer Center, Indianapolis, Indiana 46202-5289, United States
St. Vincent Indianapolis Hospital, Indianapolis, Indiana 46260, United States
Blank Children's Hospital, Des Moines, Iowa 50309, United States
Holden Comprehensive Cancer Center at University of Iowa, Iowa City, Iowa 52242-1083, United States
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States
Via Christi Cancer Center at Via Christi Regional Medical Center, Wichita, Kansas 67214, United States
Kosair Children's Hospital, Louisville, Kentucky 40232, United States
Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0293, United States
Children's Hospital of New Orleans, New Orleans, Louisiana 70118, United States
Ochsner Cancer Institute at Ochsner Clinic Foundation, New Orleans, Louisiana 70121, United States
Tulane Cancer Center, Alexandria, Louisiana 71315-3198, United States
CancerCare of Maine at Eastern Maine Medial Center, Bangor, Maine 04401, United States
Maine Children's Cancer Program, Scarborough, Maine 04074-9308, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital, Baltimore, Maryland 21215, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States
Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States
Breslin Cancer Center at Ingham Regional Medical Center, Lansing, Michigan 48910, United States
C.S. Mott Children's Hospital at University of Michigan, Ann Arbor, Michigan 48109-0238, United States
CCOP - Kalamazoo, Kalamazoo, Michigan 49007-5341, United States
Hurley Medical Center, Flint, Michigan 48503, United States
Spectrum Health Hospital - Butterworth Campus, Grand Rapids, Michigan 49503-2560, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center, Grosse Pointe Woods, Michigan 48236, United States
Children's Hospitals and Clinics of Minneapolis, Minneapolis, Minnesota 55404, United States
Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States
University of Minnesota Medical Center & Children's Hospital - Fairview, Minneapolis, Minnesota 55455, United States
University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States
Cardinal Glennon Children's Hospital, St. Louis, Missouri 63104, United States
Children's Mercy Hospital, Kansas City, Missouri 64108, United States
Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia, Missouri 65203, United States
Siteman Cancer Center at Barnes-Jewish Hospital, St. Louis, Missouri 63110, United States
Children's Hospital of Omaha, Omaha, Nebraska 68114-4113, United States
Sunrise Hospital and Medical Center, Las Vegas, Nevada 89109-2306, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756-0002, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, United States
Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States
Newark Beth Israel Medical Center, Newark, New Jersey 07112, United States
Overlook Hospital, Morristown, New Jersey 07962, United States
St. Barnabas Medical Center Cancer Center, Livingston, New Jersey 07039, United States
St. Joseph's Hospital and Medical Center, Paterson, New Jersey 07503, United States
University of New Mexico Cancer Research and Treatment Center, Albuquerque, New Mexico 87131-5636, United States
Prince of Wales Private Hospital, Randwick, New South Wales 2031, Australia
Herbert Irving Comprehensive Cancer Center at Columbia University, New York, New York 10032, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States
Maimonides Cancer Center at Maimonides Medical Center, Brooklyn, New York 11219, United States
New York Medical College, Valhalla, New York 10595, United States
NYU Cancer Institute at New York University Medical 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 11040, United States
Stony Brook University Cancer Center, Stony Brook, New York 11794-8174, United States
SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States
Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States
Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States
Leo W. Jenkins Cancer Center at ECU Medical School, Greenville, North Carolina 27835-6028, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599-7295, United States
Mission Hospitals - Memorial Campus, Asheville, North Carolina 28801, United States
Wake Forest University Comprehensive Cancer Center, Winston-Salem, North Carolina 27157-1096, United States
CCOP - MeritCare Hospital, Fargo, North Dakota 58122, United States
IWK Health Centre, Halifax, Nova Scotia B3K 6R8, Canada
Children's Hospital Medical Center of Akron, Akron, Ohio 44308-1062, United States
Children's Medical Center - Dayton, Dayton, Ohio 45404-1815, United States
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States
Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195-5217, United States
Medical University of Ohio Cancer Center, Toledo, Ohio 43614, United States
Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106-5000, United States
Tod Children's Hospital - Forum Health, Youngstown, Ohio 44501, United States
Oklahoma University Medical Center, Oklahoma City, Oklahoma 73104, United States
Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, Ontario K7L 3N6, Canada
Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8L1, Canada
McMaster Children's Hospital at Hamilton Health Sciences, Hamilton, Ontario L8N 3Z5, Canada
Legacy Emanuel Hospital and Health Center & Children's Hospital, Portland, Oregon 97227, United States
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-9786, United States
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Geisinger Medical Center, Danville, Pennsylvania 17822-0001, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, United States
St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134-1095, United States
Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada
Montreal Children's Hospital at McGill University Health Center, Montreal, Quebec H3H 1P3, Canada
Rhode Island Hospital Comprehensive Cancer Center, Providence, Rhode Island 02903, United States
Allan Blair Cancer Centre at Pasqua Hospital, Regina, Saskatchewan S4T 7T1, Canada
Saskatoon Cancer Centre at the University of Saskatchewan, Saskatoon, Saskatchewan S7N 4H4, Canada
Greenville Hospital System Cancer Center, Greenville, South Carolina 29605, United States
Hollings Cancer Center at Medical University of South Carolina, Charleston, South Carolina 29425, United States
Sioux Valley Hospital and University of South Dakota Medical Center, Sioux Falls, South Dakota 57117-5039, United States
East Tennessee Children's Hospital, Knoxville, Tennessee 37916, United States
East Tennessee State University Cancer Center at Johnson City Medical Center, Johnson City, Tennessee 37604, United States
St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States
Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-6310, United States
Baylor University Medical Center - Houston, Houston, Texas 77030-2399, United States
CCOP - Scott and White Hospital, Temple, Texas 76508, United States
Children's Hospital of Austin, Austin, Texas 78701, United States
Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104-9958, United States
Covenant Children's Hospital, Lubbock, Texas 79410, United States
M.D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States
Medical City Dallas Hospital, Dallas, Texas 75230, United States
Methodist Children's Hospital of South Texas, San Antonio, Texas 78229-3993, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas, Texas 75390, United States
Texas Tech University Health Sciences Center School of Medicine - Amarillo, Amarillo, Texas 79106, United States
University of Texas Health Science Center at San Antonio, San Antonio, Texas 78207, United States
Fletcher Allen Health Care - University Health Center Campus, Burlington, Vermont 05405, United States
Children's Hospital of The King's Daughters, Norfolk, Virginia 23507-1971, United States
INOVA Fairfax Hospital, Fairfax, Virginia 22031, United States
University of Virginia Cancer Center at UV Health System, Charlottesville, Virginia 22908, United States
Virginia Commonwealth University Massey Cancer Center, Richmond, Virginia 23298-0037, United States
Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States
Mary Bridge Children's Hospital and Health Center - Tacoma, Tacoma, Washington 98405, United States
Edwards Comprehensive Cancer Center at Cabell Huntington Hospital, Huntington, West Virginia 25701, United States
Mary Babb Randolph Cancer Center at West Virginia University Hospitals, Morgantown, West Virginia 26506, United States
Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia
Marshfield Clinic - Marshfield Center, Marshfield, Wisconsin 54449, United States
Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States
University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792-6164, United States
Malogolowkin MH, Katzenstein H, Krailo MD, Chen Z, Bowman L, Reynolds M, Finegold M, Greffe B, Rowland J, Newman K, Womer RB, London WB, Castleberry RP. Intensified platinum therapy is an ineffective strategy for improving outcome in pediatric patients with advanced hepatoblastoma. J Clin Oncol. 2006 Jun 20;24(18):2879-84.
