Survival Benefit of Temozolomide Plus Irinotecan as Second-Line Therapy in Small Cell Lung Cancer: A Retrospective...

Background: Small cell lung cancer (SCLC) is an aggressive type of cancer known for its rapid progression and poor prognosis. While several chemotherapeutic agents, including topotecan, are approved for use in the second-line treatment setting, their clinical benefits have been modest and often limited by toxicity. As a result, there is a significant need for more effective treatment strategies. Given the high rate of brain metastases in patients with SCLC and temozolomide's (TMZ) ability to penetrate the central nervous system, combining TMZ with irinotecan (IRI) presents a potentially effective therapeutic approach. This study aimed to evaluate the clinical outcomes of the TMZ and IRI combination compared to other second-line treatment regimens in a real-world patient population. Methods: We conducted a retrospective review of the medical records of 37 patients with relapsed SCLC who underwent second-line therapy at a tertiary oncology center from January 2018 to December 2023. Among these patients, 24 were treated with a combination of TMZ+IRI, while 13 received alternative regimens, which included topotecan, irinotecan, paclitaxel, docetaxel, vinorelbine, or gemcitabine. We collected baseline demographic and clinical data and assessed survival outcomes. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and prognostic factors were analyzed using Cox regression models. Results: A total of 37 patients were included (mean age 59.7 years, 86.5% male). Baseline characteristics were similar between groups, except for body mass index, which was higher in the TMZ+IRI group (27.9 vs. 24.6, p = 0.033). Median OS was significantly longer in patients treated with TMZ+IRI compared to controls (25 vs. 8 months, p = 0.002). One-year OS rates were 58.2% and 25.4%, respectively. In multivariate analysis, brain metastases (HR 0.37, 95% CI 0.14-0.95, p = 0.039) and receipt of non-TMZ+IRI regimens (HR 2.82, 95% CI 1.03-7.72, p = 0.044) were independent predictors of poor OS. Median PFS did not differ significantly between groups (8 vs. 7 months, p = 0.733), and no independent predictors of PFS were identified. Conclusions: The combination of temozolomide and irinotecan was associated with a significant overall survival benefit compared with other second-line regimens in relapsed SCLC, despite similar progression-free survival. These findings suggest that TMZ+IRI may provide a clinically meaningful option for appropriately selected patients, particularly those with preserved performance status. Prospective randomized studies are warranted to confirm these results and better define the role of this regimen in treatment sequencing.