Doxorubicin paclitaxel in pretreated advanced small-cell lung cancer: a large real-life retrospective study

Small-cell lung cancer (SCLC) is a highly aggressive disease with limited treatment options beyond first-line platinum-based chemotherapy. Although various second-line regimens such as topotecan and cyclophosphamide-adriamycin-vincristine have been evaluated, clinical outcomes remain poor, particularly in patients with platinum-resistant or refractory disease. The combination of paclitaxel and doxorubicin showed encouraging results in early-phase trials, but data on its use in real-world settings are lacking. This study aimed to assess the efficacy and safety of this chemotherapy regimen in patients with previously treated SCLC in a real-world clinical setting.

Data were retrospectively collected from all consecutive patients with previously treated SCLC at a single institution in France between 2000 and 2024.

A total of 149 patients were included, of whom 79.9% had platinum-resistant or refractory disease at the time of paclitaxel-doxorubicin initiation. The median progression-free survival (PFS) was 2.4 months [95% confidence interval (CI): 2.1-3.8], and the median overall survival (OS) was 5.1 months (95% CI: 4.7-6.0). The objective response rate was 22.2% in the overall population and 27.7% when excluding patients not evaluable for response. The disease control rate was 41.6% including all patients and 52.1% when excluding non-evaluable cases. In multivariable analysis, an Eastern Cooperative Oncology Group performance status of 2-4 compared to 0-1 was associated with shorter PFS [hazard ratio (HR) =1.9, 95% CI: 1.22-2.8, P=0.004] and OS (HR =2.73, 95% CI: 1.76-4.2, P<0.001). Adverse events led to dose reductions in 54.9% of patients, primarily due to general deterioration, hematologic toxicity, or neuropathy. No treatment-related deaths were reported.

This real-world study suggests that the paclitaxel-doxorubicin combination provides some clinical activity in previously treated SCLC, including in platinum-resistant/refractory disease. Although toxicities were common, they were generally manageable. These findings support further investigation of this regimen with careful patient selection.