Clinical Outcomes and Prognostic Factors to Predict Treatment Response in High Risk Neuroblastoma Patients Receiving Topotecan and Cyclophosphamide Containing Induction Regimen: a Prospective Multicenter Study.

Background Neuroblastoma is the most common extra-cranial solid tumor among children. Despite intensive treatment, patients with advanced disease mostly experience dismal outcomes. Here, we proposed the use of topotecan and cyclophosphamide containing induction regimen as an upfront therapy to high risk neuroblastoma patients. Methods Patients with high risk neuroblastoma undergoing ThaiPOG high risk neuroblastoma protocol from 2016 to 2017 were studied. All patients received 6 cycles of induction regimen consisting of 2 cycles topotecan (1.2 mg/m 2 /day) and cyclophosphamide (400 mg/m 2 /day) for 5 days followed by cisplatin (50 mg/m 2 /day) for 4 days combined with etoposide (200 mg/m 2 /day) for 3 days on the third and fifth cycles and cyclophosphamide (2100 mg/m 2 /day) for 2 days combined with doxorubicin (25 mg/m 2 /day) and vincristine (0.67 mg/m 2 /day) for 3 days on the fourth and sixth cycles. Treatment response after the 5th cycle before surgery and treatment-related toxicities after each topotecan containing induction cycle were evaluated. Relevant prognostic factors were analyzed to measure the treatment response among those patients. Results In all, 107 high risk neuroblastoma patients were enrolled in the study. After the 5th cycle of induction regimen, the patients achieved complete response ( N = 2), very good partial response ( N = 40), partial response ( N = 46) and mixed response ( N = 19). None of the patients experienced stable disease or disease progression. The most significant prognostic factor was type of healthcare system. The most common adverse effect was febrile neutropenia followed by mucositis, diarrhea and elevated renal function. Conclusion The topotecan and cyclophosphamide containing induction regimen effectively provides favorable treatment response. The regimen is well tolerated with minimal toxicity among patients with high risk neuroblastoma in Thailand.