Assessment of response and toxicity for recurrent glioblastoma to single-agent Lomustine (CCNU) – A single centre experience


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Chevonne Tan1, Helen Wong2, Helen Flint2, Eswar Chinnamani2, Chloe May2, Aditya Shenoy2, Shaveta Mehta2
1Hull University Teaching Hospitals NHS Trust, 2Clatterbridge Cancer Centre NHS Foundation Trust

Abstract

Background

Lomustine (CCNU) based regimens are frequently used for recurrent glioblastoma multiforme (GBM). Single-agent oral CCNU is widely used as 100-130mg/m2, day 1 x 6-weekly cycle for up to 6 cycles. Efficacy is limited, with median progression free survival of around 1.0-3.0 months with higher haematological toxicities, particularly thrombocytopenia around 13-25% with the standard regimens. The Clatterbridge Cancer Centre, UK, has adopted a regimen of 40mg once a day over 4 days x 4-weekly for up to 6 cycles. This study aims to identify the efficacy and toxicity profile of our regimen in recurrent GBM.

Method

A retrospective analysis on 113 recurrent GBM patients, treated with single-agent CCNU as a second line, between June 2016 and January 2020. SPSS v.27 was used for Kaplan-Meier survival estimates identifying Progression free survival (PFS) and Overall Survival (OS).

Overall Responses were based on imaging or clinical assessment in patients with at least 2 cycles of CCNU. Clinical adverse events were identified through SACT assessments and blood test records, based on the CTCAE v5.0 grading.

Results

We observed an overall response rate of 18.8% with 2.4% partial response and 16.5% stable disease. The CCNU-specific median OS was 8 months, median PFS was 4 months, and PFS6 (percentage of patients who are progression free at 6 months) of 20.4%.

In our experience, the regimen was well tolerated with the commonest toxicity being grade 1 fatigue (38.9%). The rate of Grade 3 or 4 haematological toxicities was low with thrombocytopenia in 12% and neutropenia in 2.7% of patients.

Conclusion

This study shows this regimen is a good alternative to the common regimens, due to better tolerance, lower rates of toxicity and equivalent efficacy. We propose that further prospective studies should be considered to compare differing CCNU regimens in glioma patients to mitigate retrospective studies’ limitations.

Impact statement

This study shows this regimen is a good alternative to the common regimens, due to better tolerance, lower rates of toxicity and equivalent efficacy.