Actual body weight dosing of temozolomide and overall survival in patients with glioblastoma

J Oncol Pharm Pract. 2021 Oct;27(7):1723-1729. doi: 10.1177/1078155220968613. Epub 2020 Oct 29.

Abstract

Background: Adult glioblastoma patients receiving standard radiation therapy and concurrent temozolomide chemotherapy have a median survival of 14.6 months. Based on the pivotal trial data by Stupp et al., temozolomide doses were calculated based on body surface area. However, no details regarding the weight used to calculate body surface area was included in the study. As a result, temozolomide doses have been variable across the province.

Methods: This retrospective chart review was conducted to determine the correlation between dose of first line temozolomide with overall survival. Patients between January 1st, 2009 and December 31st, 2014 who were newly diagnosed, pathology confirmed glioblastoma treated first line with temozolomide within Alberta Health Services were included in the study. Temozolomide doses above and below determined cut points were compared through the Kaplan-Meier method, then assessed using the log-rank test.

Results: A cut point of 97.8% of actual body weight calculated body surface area dosing was determined for concurrent phase temozolomide. At doses above this cut point, there was a statistically significant (p = 0.0158) increase of 0.3 years in median overall survival. As for toxicity concerns, there was a statistically significant increase in the proportion of temozolomide dose reductions due to toxicity in patients dosed above the cut point.

Conclusion: Temozolomide doses at full actual body weight calculated body surface area dosing during the concurrent phase is required to achieve a similar median OS as seen in the pivotal trial by Stupp et al.

Keywords: Glioblastoma; actual body weight; dosing; overall survival; temozolomide.

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Body Weight
  • Brain Neoplasms* / drug therapy
  • Combined Modality Therapy
  • Dacarbazine / therapeutic use
  • Glioblastoma* / drug therapy
  • Humans
  • Retrospective Studies
  • Temozolomide / therapeutic use

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide