Outcome of temozolomide in relapsed small cell lung cancer: A retrospective single center analysis

Extensive-stage small cell lung cancer (SCLC) has a dismal prognosis. Despite initial responsiveness to first-line platinum-etoposide chemotherapy, most patients relapse within six months. Managing disease progression, particularly in platinum-resistant or refractory cases, remains challenging. Topotecan is the only drug approved in the European Union for the second-line treatment of SCLC but is associated with modest clinical activity and high rates of hematological toxicities. Temozolomide, an oral alkylating agent, has been investigated as a viable alternative for treating relapsed SCLC. This study presents the largest real-world cohort of SCLC-patients treated with temozolomide.

We performed a retrospective analysis of patients with relapsed SCLC treated with temozolomide at a single academic hospital in Belgium. Temozolomide was administered at a fixed dose of 250 mg orally once daily on days 1-5 of each 28-day cycle. Data on activity (overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS) and median overall survival (mOS)) and safety (treatment related adverse events (TRAE)) were collected.

Between February 2011 and May 2023, a total of 48 patients with relapsed SCLC were treated with temozolomide of which 47 patients, median age 61 years, were included in this real-world analysis. The majority of the patients were heavily pretreated with 57.4 % having received two or more prior systemic therapies. An objective response was observed in 14.9 % and the DCR was 23.4 %. The median PFS was 1.7 months (95 % CI 1.5-1.9) and the median OS was 3.2 months (95 % CI 2.3-4.1). Grade 3-4 TRAEs occurred in 34 % of the patients.

Temozolomide demonstrated modest clinical activity in this real-world effectiveness analysis of patients with relapsed SCLC. Nevertheless, given its comparable response rate and milder toxicity profile compared to topotecan, temozolomide should be considered as a viable alternative to topotecan for treating relapsed SCLC.