METHODS AND MATERIALS: Patients with GCTs and treated with at least two cycles of BEP chemotherapy between January 2003 and Oct 2009 were eligible for this study. Patients received 4-6 cycles of bleomycin 30,000IU IV D1, D8 and D15 and either etoposide 100mg/m2 IV D1- D5 and cisplatin 20mg/m2 IV D1- D5 (5 day BEP regimen) or etoposide 165 mg/m2 D1- D3 and cisplatin 50mg/m2 D1-3 (3 day BEP regimen) every three weeks per cycle. All patients received prophylactic granulocyte colony-stimulating factor (GCSF) from days 6 to 10 of each cycle. The overall response rates, 2 year progression-free survival and overall survival of the whole cohort were assessed.
RESULTS: Thirty patients fulfilled the inclusion criteria. Non-seminomatous GCTs comprised 93.3% of cases and gonadal and mediastinal primary sites were the most common. Sixty percent were classified as IGCCCG poor risk disease. Median follow-up was 26.6 months. The overall response rate (CR+PR) was 70%. The two year PFS and OS were 70% and 66%. There was a significant difference in terms of the overall response rate (85% vs 40%, p = 0.03) and in PFS (94.7% vs 50%, p = 0.003) between gonadal and extragonadal primary sites.
CONCLUSION: It is possible to achieve outcomes similar to those in international clinical trials with close monitoring and good supportive care of patients undergoing BEP chemotherapy. There is a strong argument for patients with IGCCCG poor prognosis disease to be treated in specialist tertiary centres to optimize treatment outcomes.
PATIENTS AND METHODS: FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129).
RESULTS: Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; P < .0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; P < .0001) and 0.02 (95% CI, < 0.01 to 0.05; P = .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively.
CONCLUSION: Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.