Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study

Abstract

PurposeMetastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([123I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate.Materials and MethodsPatients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m2/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m2, and doxorubicin, 45 mg/m2.ResultsSixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%).ConclusionTVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.

Association of PARP1 polymorphisms with response to chemotherapy in patients with high‐risk neuroblastoma

“…No difference in event‐free survival was observed between the two regimens (Advances in Neuroblastoma Research Association Meeting, San Francisco 2018, Abstract 90). Patients were divided into two subgroups: responders and non‐responders to induction chemotherapy, according to the definition recently reported for high‐risk patients enrolled in the SIOPEN high‐risk protocol . Precisely, responders are the patients that can proceed with high‐dose chemotherapy and stem cell transplants, whereas non‐responders are the patients who cannot proceed and are referred to second line therapy.…”

Dual BRD4 and AURKA Inhibition is Synergistic against MYCN-amplified and nonamplified Neuroblastoma

“…Prior data showed the vincristine is synergistic with IBET-151 and alisertib individually 33,34 . Vincristine is used sparingly in upfront neuroblastoma therapy, due to limited single-agent efficacy, but it has improved efficacy in combination with drugs that cause cell cycle disruption [46][47][48] as occurs with BRD4 and AUKRA inhibition. Furthermore, vincristine is not significantly myelosuppressive, avoiding a toxicity associated with alisertib 17 .…”

Therapy intensification in high-risk neuroblastoma patients with poor response to standard induction: experience of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology

“…Описанный подход помог улучшить ответ у части пациентов (6,4% больных достигли ПО), что позволило им перейти к этапу высокодозной ХТ. Однако влияние описанного подхода на долгосрочную выживаемость требует дальнейшего изучения [14].…”

“…Ответ на индукционную терапию, характеризующий in vivo чувствительность опухоли к противоопухолевым препаратам, влияет также на долгосрочную выживаемость [9][10][11][12][13]. Вопрос об интенсификации лечения при плохом ответе на индукционную терапию в настоящее время изучается и требует дальнейшего обсуждения с оценкой отдаленного прогноза в данной группе пациентов [14].…”