Cancers (Jun 2021)

An Evaluation of the Tolerability and Feasibility of Combining 5-Amino-Levulinic Acid (5-ALA) with BCNU Wafers in the Surgical Management of Primary Glioblastoma

  • Colin Watts,
  • Keyoumars Ashkan,
  • Michael D. Jenkinson,
  • Stephen J. Price,
  • Thomas Santarius,
  • Tomasz Matys,
  • Ting Ting Zhang,
  • Alina Finch,
  • Peter Collins,
  • Kieren Allinson,
  • Sarah J. Jefferies,
  • Daniel J. Scoffings,
  • Athanasios Zisakis,
  • Mark Phillips,
  • Katharina Wanek,
  • Paul Smith,
  • Laura Clifton-Hadley,
  • Nicholas Counsell

DOI
https://doi.org/10.3390/cancers13133241
Journal volume & issue
Vol. 13, no. 13
p. 3241

Abstract

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Background Glioblastoma (GBM) is the commonest primary malignant brain tumour in adults and effective treatment options are limited. Combining local chemotherapy with enhanced surgical resection using 5-aminolevulinic acid (5-ALA) could improve outcomes. Here we assess the safety and feasibility of combining BCNU wafers with 5-ALA-guided surgery. Methods We conducted a multicentre feasibility study of 5-ALA with BCNU wafers followed by standard-of-care chemoradiotherapy (chemoRT) in patients with suspected GBM. Patients judged suitable for radical resection were administered 5-ALA pre-operatively and BCNU wafers at the end resection. Post-operative treatment continued as per routine clinical practice. The primary objective was to establish if combining 5-ALA and BCNU wafers is safe without compromising patients from receiving standard chemoRT. Results Seventy-two patients were recruited, sixty-four (88.9%) received BCNU wafer implants, and fifty-nine (81.9%) patients remained eligible following formal histological diagnosis. Seven (11.9%) eligible patients suffered surgical complications but only two (3.4%) were not able to begin chemoRT, four (6.8%) additional patients did not begin chemoRT within 6 weeks of surgery due to surgical complications. Eleven (18.6%) patients did not begin chemoRT for other reasons (other toxicity (n = 3), death (n = 3), lost to follow-up/withdrew (n = 3), clinical decision (n = 1), poor performance status (n = 1)). Median progression-free survival was 8.7 months (95% CI: 6.4–9.8) and median overall survival was 14.7 months (95% CI: 11.7–16.8). Conclusions Combining BCNU wafers with 5-ALA-guided surgery in newly diagnosed GBM patients is both feasible and tolerable in terms of surgical morbidity and overall toxicity. Any potential therapeutic benefit for the sequential use of 5-ALA and BCNU with chemoRT requires further investigation with improved local delivery technologies.

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