Regional Chemotherapy Is a Valuable Second-Line Approach in Metastatic Esophageal Cancer after Failure to First-Line Palliative Treatment.

BACKGROUND: Therapeutic options in metastatic esophageal cancer (EC) are limited with unsatisfactory results. We evaluated the efficacy of regional chemotherapy (RegCTx) approach in diffuse metastatic EC using arterial infusion (AI), upper abdominal perfusion (UAP) and isolated-thoracic perfusion (ITP) in 14 patients (N = 8 adenocarcinoma (AC) and N = 6 squamous cell carcinoma (SQCC)) after failure to first-line palliative treatment. METHODS: All patients had previously failed first-line palliative treatment attempt with systemic chemotherapy (sCTx). In total 51 RegCTx cycles (12 AI, 3 UAP and 36 ITP) were applied using cisplatin, Adriamycin and Mitomycin C. The outcome was evaluated using RECIST criteria with MediasStat 28.5.14 and SPSS-28.0. RESULTS: No grade III or IV hematological complications occurred. The overall response rate was 41% partial response, 27% stable and 32% progressive disease. Median overall survival (OS) was 38 months (95%CI 10.1-65.9). The OS was better in SQCC with 51 months The RegCTx specific survival was 13 months (95%CI 2.9-23.1) in the entire cohort and 25 months in SQCC patients. CONCLUSION: RegCTx is a valuable safe approach and superior to the current proposed therapeutic options in metastatic EC after failure to first-line therapy.

Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines.

Makaluvamines are pyrroloiminoquinones isolated from Zyzzya sponges. Until now, they have been described as topoisomerase II inhibitors with cytotoxic effects in diverse tumor cell lines. In the present work, seven makaluvamines were tested in several antioxidant assays in primary cortical neurons and neuroblastoma cells. Among the alkaloids studied, makaluvamine J was the most active in all the assays. This compound was able to reduce the mitochondrial damage elicited by the well-known stressor H2O2. The antioxidant properties of makaluvamine J are related to an improvement of the endogenous antioxidant defenses of glutathione and catalase. SHSY5Y assays proved that this compound acts as a Nrf2 activator leading to an improvement of antioxidant defenses. A low concentration of 10 nM is able to reduce the reactive oxygen species release and maintain a correct mitochondrial function. Based on these results, non-substituted nitrogen in the pyrrole plus the presence of a p-hydroxystyryl without a double bond seems to be the most active structure with a complete antioxidant effect in neuronal cells.