A new schedule of temozolomide as second-line therapy in neuroendocrine carcinomas patients with a poor performance status: a phase II trial

Abstract Background: Second-line treatment for neuroendocrine carcinoma (NEC) has been investigated in retrospective trials, with a few prospective ongoing trials. Therefore, there is no consensus on the second-line regimen for patients with progressive NEC. These patients generally have poor performance status and low tolerance to combination therapy. Metronomic temozolomide showed, in retrospective trials, a good safety and efficacy profile. Patients and methods: TENEC trial is a single-arm, phase II study in platinum-pre-treated recurrent and metastatic NEC patients. Patients were treated with temozolomide 75 mg/m2/day by mouth for seven days followed by seven days of no treatment (one week on/ one week off regime). The primary endpoint was overall response rate analyzed by the Kaplan-Meier method, and the secondary endpoints were median progression-free survival (PFS), median overall survival (OS), safety and tolerability. Results: Thirty-eight patients received TMZ 75 mg/m2/day one week on one week off within the TENEC trial. The overall response rate was 18% (n=7). One complete response and six partial responses were achieved. The median PFS was 6.5 months (95% CI: 5.1–14.5), and the median OS was 12 months (95% CI: 5.6–20.8). The 1-year PFS rate was 37%. No statistically significant difference in median OS (p=0.81, hazard ratio [HR] 95% CI: 0.5–1.9) and median PFS (p=0.85, HR 95% CI: 0.4–2) was observed among patients with Ki67 <55% vs ≥55%. Any grade’s most common adverse events were nausea, diarrhea and abdominal pain. Conclusion: Metronomic temozolomide has an encouraging efficacy and safety profile as a second-line treatment in NEC.