RESUMEN
BACKGROUND: The purpose of this study was to evaluate the clinical, biological and radiological responses to, and tolerability of, conventional transarterial chemoembolization (cTACE) using streptozocin for unresectable neuroendocrine liver metastases. PATIENTS AND METHODS: A total of 52 patients with predominant liver disease were treated with cTACE using an emulsion of streptozocin, Lipiodol and embolization particles. A sequential approach was favored in patients with high liver tumor burden. Clinical, biological and radiological responses were evaluated using carcinoid symptoms, biomarkers and mRecist criteria, respectively. RESULTS: A total of 127 procedures were performed with a sequential approach in 65% of patients. All patients received streptozocin and Lipiodol. Carcinoid syndrome was improved in 69% of patients after treatment (p = 0.01). Post-embolization syndrome was reported in 78% of patients. At the end of all cTACE, objective response and non-progressive disease were 32% and 70%, respectively. Progression-free survival was 18.3 ± 13.3 months (median 14.9) and median overall survival (OS) from start of treatment was 74 months. The OS at 1 year, 2 years, 3 years and 5 years was 91% (IC = 84-99%), 84% (CI = 72-95%), 69% (CI = 53-84%) and 63% (C = 46-81%), respectively. CONCLUSIONS: cTACE using streptozocin is an effective and well-tolerated palliative option for patients with neuroendocrine liver metastases, associated with prolonged survival and delayed time to progression.
RESUMEN
Androgen-dependent and castration-resistant prostate cancer (PC) is usually sensitive to docetaxel chemotherapy. Nevertheless, docetaxel resistance frequently appears after several cycles of treatment, raising the problem of salvage treatment for docetaxel-resistant PC patients. Although the combination of docetaxel and estramustine prolongs metastasis-free and overall survival of patients with androgen-independent PC, the use of this modality remains limited in elderly patients or patients with several comorbidities, especially vascular disease or gastrointestinal toxicity, because of unacceptable toxicity including venous thrombosis. The aims of this study were therefore (i) to evaluate the in-vivo efficacy of estramustine combined with docetaxel since initial tumor growth and following the appearance of docetaxel resistance in the androgen-dependent human PC xenograft PAC120, and (ii) to evaluate the efficacy of estramustine in six human androgen-independent PC models derived from PAC120. In docetaxel-resistant tumor-bearing mice, estramustine alone induced a TGD2 of 18 days, whereas the combination of docetaxel and estramustine induced a TGD2 of 50 days (P<0.05) with no significantly different overall survival of mice treated by docetaxel and estramustine since day 1 or since the onset of resistance to docetaxel. Among the six human androgen-independent tumors treated with estramustine alone, two highly sensitive models, two intermediate responding tumors, and two resistant models were observed. Altogether, these results suggest that estramustine should be combined with docetaxel in PC patients, but the use of this treatment could be limited, particularly in elderly patients, to docetaxel-resistant cases.