A new schedule of one week on/one week off temozolomide as second-line treatment of advanced neuroendocrine carcinomas (TENEC-TRIAL): a multicenter, open-label, single-arm, phase II trial.

BACKGROUND: There is no consensus on the second-line treatment of patients with progressive high-grade neuroendocrine neoplasms (NENs G3) and large-cell lung neuroendocrine carcinoma. These patients generally have poor performance status and low tolerance to combination therapy. In this trial, we aim to evaluate the efficacy and safety of temozolomide given every other week in patients with advanced platinum-pretreated NENs G3. PATIENTS AND METHODS: This trial is an open-label, non-randomized, phase II trial. Patients with platinum-pretreated metastatic neuroendocrine carcinoma were treated with 75 mg/m2/day of temozolomide for 7 days, followed by 7 days of no treatment (regimen one week on/one week off). The primary endpoint was the overall response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety and tolerability. This study is registered with ClinicalTrials.gov, NCT04122911. RESULTS: From 2017 to 2020, 38 patients were enrolled. Among the patients with determined Ki67, 12 out of 36 (33.3%) had a Ki67 index <55% and the remaining 24 out of 36 (66.6%) had an index ≥55%. Overall response rate was 18% (7/38), including one complete response and six partial responses. The median PFS was 5.86 months [95% confidence interval (CI) 4.8 months-not applicable) and the median OS was 12.1 months (95% CI 5.6-20.4 months). The 1-year PFS rate was 37%. No statistically significant difference in median PFS [hazard ratio 1.3 (95% CI 0.6-2.8); P = 0.44] and median OS [hazard ratio 1.1 (95% CI 0.5-2.4); P = 0.77] was observed among patients with Ki67 <55% versus ≥55%. Only G1-G2 adverse events were registered, the most common being G1 nausea, diarrhea and abdominal pain. CONCLUSION: One week on/one week off temozolomide shows promising activity in patients with poorly differentiated NEN. The good safety profile confirmed the possibility of using this scheme in patients with poor performance status.

First-line chemotherapy with liposomal doxorubicin plus cyclofosfamide in metastatic breast cancer: a case report of early and prolonged response.

The treatment choice for metastatic breast cancer should consider the appropriate balance between efficacy and toxicity of the therapy. We discuss a clinical case with an early response and prolonged to liposomal anthracyclines-based chemotherapy, without cardiotoxicity, enhancing the evidence of safety of liposomal formulation to prevent heart damage. Moreover, the case seems to be of interest for the role of 18F-FDG-PET in clinical response assessment: an early decrease of the standardized uptake value value, even before conventional imaging evaluation, is highly predictive for prolonged clinical response.