{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T18:48:55Z","timestamp":1773773335870,"version":"3.50.1"},"reference-count":23,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"18","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2006,6,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> The INT-0098 Intergroup Liver Tumor Study demonstrated no statistically significant differences in event-free and overall survival between patients randomized to treatment with either cisplatin + fluorouracil + vincristine (C5V) or cisplatin + doxorubicin. Results from this and other therapeutic trials suggested that cisplatin was the most active agent against hepatoblastoma. To increase the platinum dose-intensity, a novel regimen was developed alternating carboplatin and cisplatin (CC) every 2 weeks. The P9645 study was designed to compare the risk of treatment failure for patients with stage III\/IV hepatoblastoma randomized to either C5V or CC. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> C5V was given according to INT-0098 and CC consisted of carboplatin at 700 mg\/m<jats:sup>2<\/jats:sup> on day 0 (560 mg\/m<jats:sup>2<\/jats:sup> after two cycles) followed by cisplatin 100 mg\/m<jats:sup>2<\/jats:sup> on day 14. Granulocyte colony-stimulating factor was used after each CC cycle. All patients received four to six cycles of chemotherapy. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> From the time the study was opened until the time that random assignment was halted, 56 patients received CC and 53 patients received C5V. The 1-year event-free survival was 37% for patients receiving CC and 57% for those receiving C5V (P = .017). Patients randomly assigned to CC required more blood product support. As a result of a semiannual review by the Children's Oncology Group Data and Safety Monitoring Committee, random assignment was discontinued after 3 years of enrollment because the projected improvement in long-term outcome associated with CC was statistically excluded as a possible outcome of this trial. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Intensification of therapy by alternating platinum analogs increased the risk of adverse outcome in children with unresectable or metastatic hepatoblastoma. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.02.6013","type":"journal-article","created":{"date-parts":[[2006,6,16]],"date-time":"2006-06-16T23:34:12Z","timestamp":1150500852000},"page":"2879-2884","source":"Crossref","is-referenced-by-count":85,"title":["Intensified Platinum Therapy Is an Ineffective Strategy for Improving Outcome in Pediatric Patients With Advanced Hepatoblastoma"],"prefix":"10.1200","volume":"24","author":[{"given":"Marcio H.","family":"Malogolowkin","sequence":"first","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; Children's..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard","family":"Katzenstein","sequence":"additional","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; Children's..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark D.","family":"Krailo","sequence":"additional","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; Children's..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengjia","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; Children's..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Bowman","sequence":"additional","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; Children's..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marleta","family":"Reynolds","sequence":"additional","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; Children's..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milton","family":"Finegold","sequence":"additional","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; Children's..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Greffe","sequence":"additional","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; Children's..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon","family":"Rowland","sequence":"additional","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; Children's..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt","family":"Newman","sequence":"additional","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; Children's..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard B.","family":"Womer","sequence":"additional","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; Children's..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy B.","family":"London","sequence":"additional","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; Children's..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Castleberry","sequence":"additional","affiliation":[{"name":"From the Childrens Hospital Los Angeles; University of Southern California Keck School of Medicine, Los Angeles; Children's Oncology Group Operations Center, Arcadia; Children's Hospital Oakland, Oakland, CA; Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Children's Memorial Medical Center at Chicago, Chicago, IL; Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX; The Children's Hospital, Denver, CO; Children's National Medical Center, Washington, DC; 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