RESUMO
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.
RESUMO
AIMS AND BACKGROUND: Sentinel lymph node (SLN) detection is currently employed in patients with malignant melanoma (MM) to spare them unnecessary lymph node dissection. METHODS AND STUDY DESIGN: We investigated 241 patients (130 men and 111 women, median age, 50 years (range, 14-92) with MM (192 before and 51 after surgical biopsy); two of them had more than one melanoma lesion. In each patient approx. 10 MBq of 99mTc Nanocoll in 0.1 mL (Nycomed Amersham Sorin; particle size range, 3-80 nm) was injected intradermally around the MM lesion or surgical scar. Dynamic acquisition was performed for 20 minutes (20 frames/min) and the study was concluded within four hours of injection. Using an external radioactive marker, the skin over the SLN was marked with China ink. RESULTS: 294 SLNs were scintigraphically identified: 117 in the inguinal region, 147 in the axillae, four in the submandibular region, three in the laterocervical region and 23 at other sites. In two patients no drainage was detected. In 43 patients more than one sentinel node was identified. In 13 patients with lesions located in the trunk the tracer drained towards multiple lymph node stations or unexpected lymph nodes (nine cases). Histology and immunohistochemistry diagnosed MM in 25 SLNs; 19 were positive for metastasis with hematoxylin-eosin staining, five with Hmb45 and one with CD68 immunostaining. All 25 detected lymphatic basins were excised. In nine of these basins there was metastatic involvement of at least one other lymph node besides the SLN. During follow-up which ranged from six to 86 months, metastatic disease was found in only one patient with a histologically negative SLN six months after surgery. CONCLUSIONS: This study confirms the utility of scintigraphic SLN detection in patients with MM. In most of the cases the procedure led the surgeon to evaluate the drainage area, which is unpredictable for lesions in the trunk and may be difficult to delineate using only patent blue dye. Furthermore, in approximately 10% of cases we observed dual drainage from individual lesions, mainly those located on the trunk. We will proceed to compare the results obtained during follow-up with those of an investigational group of patients with melanoma who were not subjected to lymphoscintigraphy for SLN detection in order to obtain well-founded information on the prognostic value of this technique.
