Background.

Despite recent advances, survival in patients with glioblastoma remains poor. Outside clinical trials,
lomustine is commonly considered standard of care in recurrent disease. However, comparative data between
lomustine and other chemotherapy regimens are limited.

Methods.

We performed a retrospective multicenter cohort study including patients from seven certified
neuro-oncology centers in Germany to compare lomustine monotherapy with combination therapy using lomustine
and procarbazine in first recurrence of glioblastoma. Propensity score matching was applied to obtain comparable
groups based on sex, age, extent of resection at primary diagnosis, Karnofsky performance status at the start of
recurrence therapy, and MGMT promoter methylation status. Post-recurrence survival (PRS) and progression-free
survival (PFS) were analyzed using Kaplan-Meier estimation and multivariable Cox regression analysis.

Results.

Seventy-seven patients were matched in each treatment group. PRS was comparable, with a median of 11.6
months for lomustine monotherapy and 10.0 months for lomustine plus procarbazine (log-rank test, P = .120).
Multivariable Cox regression showed no significant difference (HR 1.33, 95% CI, 0.93-1.90, P = .123). PFS was shorter
in patients receiving combination therapy compared to monotherapy (3.7 vs. 5.1 months, log-rank test, P = .042).
Multivariable Cox regression did not reveal significant differences (HR 1.31, 95% CI, 0.90-1.90, P = .166).

Conclusions.

Our data indicates that potential additive toxicity by intensified combination chemotherapy should be
avoided due to lack of efficacy compared to lomustine monotherapy.