Reduced and Compressed Cisplatin-Based Chemotherapy in Children and Adolescents With Intermediate-Risk Extracranial Malignant Germ Cell Tumors: A Report From the Children's Oncology Group

• Authors: Furqan Shaikh, University of Toronto; John W. Cullen, Rocky Mountain Hospital for Children-Presbyterian Saint Luke’s Medical Center; Thomas Olson, Emory University; Farzana Pashankar, Yale University; Marcio H. Malogolowkin, University of California Davis; James F. Amatruda, University of Texas Southwestern Medical Center; Doojduen Villaluna, Children’s Oncology Group; Mark Krailo, Children’s Oncology Group; Deborah F. Billmire, Riley Hospital for Children; Frederick J. Rescorla, Riley Hospital for Children; Rachel A. Egler, Rainbow Babies and Children’s Hospital; Bryan J. Dicken, Stollery Children’s Hospital; Jonathan H. Ross, Rainbow Babies and Children’s Hospital; Marc Schlatter, Spectrum Health; Carlos Rodriguez-Galindo, St Jude Children’s Research Hospital; A. Lindsay Frazier, Dana-Farber Cancer Institute
• Journal Title: Journal of Clinical Oncology
• Volume: Volume 35, Number 11
• Publisher: American Society of Clinical Oncology | 2017-04-10, Pages 1203-1210
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1200/JCO.2016.67.6544
• Subjects: Health Sciences, Oncology; Health Sciences, General
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; TESTICULAR CANCER; STAGE-I; COMBINATION CHEMOTHERAPY; PEDIATRIC INTERGROUP; RANDOMIZED-TRIAL; INITIAL SURGERY; UNITED-KINGDOM; BLEOMYCIN; ETOPOSIDE; RECOMMENDATIONS

Abstract

Purpose To investigate whether event-free survival (EFS) can be maintained among children and adolescents with intermediate-risk (IR) malignant germ cell tumors (MGCT) if the administration of cisplatin, etoposide, and bleomycin (PEb) is reduced from four to three cycles and compressed from 5 to 3 days per cycle. Patients and Methods In a phase 3, single-arm trial, patients with IR MGCT (stage II-IV testicular, II-III ovarian, I-II extragonadal, or stage I gonadal tumors with subsequent recurrence) received three cycles of PEb. A parametric comparator model specified that the observed EFS rate should not be significantly < 92%. As recommended for trials that test a reduction of therapy, a one-sided P value ≤ .10 was used to indicate statistical significance. In a post hoc analysis, we also compared results to the EFS rate of comparable patients treated with four cycles of PEb in two prior studies. Results Among 210 eligible patients enrolled from 2003 to 2011, 4-year EFS (EFS 4 ) rate was 89% (95% confidence interval, 83% to 92%), which was significantly lower than the 92% threshold of the comparison model (P = .08). Among 181 newly diagnosed patients, the EFS 4 rate was 87%, compared with 92% for 92 comparable children in the historical cohort (P = .15). The EFS 4 rate was significantly associated with stage (stage I, 100%; stage II, 92%; stage III, 85%; and stage IV, 54%; P < .001). Conclusion The EFS rate for children with IR MGCT observed after three cycles of PEb was less than that of a prespecified parametric model, particularly for patients with higher-stage tumors. These data do not support a reduction in the number of cycles of PEb from four to three. However, further investigation of a reduction in the number of cycles for patients with lower-stage tumors is warranted.