Safety and efficacy of concurrent carboplatin during full-dose craniospinal irradiation for high-risk/metastatic medulloblastoma in a resource-limited setting

Pediatr Blood Cancer. 2021 May;68(5):e28925. doi: 10.1002/pbc.28925. Epub 2021 Feb 3.

Abstract

Purpose: To assess the safety and efficacy of concurrent carboplatin during craniospinal irradiation (CSI) in high-risk/metastatic medulloblastoma defined as either residual tumor >1.5 cm2 or leptomeningeal metastases.

Methods: This single-arm combined prospective (2005-2011) and retrospective (2011-2019) study was undertaken at a tertiary care cancer center in India. Following surgery, patients with newly diagnosed high-risk/metastatic medulloblastoma received concurrent carboplatin (35 mg/m2 ) for 15 days (day 1 to day 15) during CSI plus posterior fossa/tumor bed boost, followed by six cycles of standard adjuvant chemotherapy.

Results: All 97 patients completed their planned course of radiotherapy without interruptions, except for two (2.1%) patients who had brief gaps due to treatment-related toxicity. Grade 3-4 anemia, neutropenia, thrombocytopenia, and febrile neutropenia were seen in four (4.1%), 41 (42.2%) 21 (21.6%), and 18 (18.6%) patients, necessitating packed cell transfusion, granulocyte colony-stimulating factor, and platelet support in five (5.1%), 41 (42.2%), and five (5.1%) patients, respectively, during the concurrent phase. Following myelorecovery, 92 (94.9%) patients completed the planned six cycles of standard adjuvant systemic chemotherapy. There were no treatment-related deaths during the concurrent chemo-radiotherapy phase, while three (3.1%) toxic deaths were ascribed to adjuvant chemotherapy-related complications. At a median follow-up of 82 months, the 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 60.2% and 62.1%, respectively. On univariate analysis, leptomeningeal metastases (M0/M1 vs. M2/M3) and histological subtype (large cell/anaplastic vs. others) emerged as significant prognostic factors for survival.

Conclusion: Addition of concurrent carboplatin to RT as radiosensitizing chemotherapy is a simple and effective way of treatment intensification in high-risk/metastatic medulloblastoma.

Keywords: carboplatin; concurrent; craniospinal irradiation; high risk; leptomeningeal metastases; medulloblastoma.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Agents / administration & dosage*
  • Carboplatin / administration & dosage*
  • Cerebellar Neoplasms / therapy*
  • Chemoradiotherapy / methods*
  • Chemotherapy, Adjuvant / methods
  • Child
  • Craniospinal Irradiation / methods
  • Female
  • Humans
  • Male
  • Medulloblastoma / therapy*

Substances

  • Antineoplastic Agents
  • Carboplatin