| Autor: |
Suleiman, Yaman, Mahipal, Amit, Shibata, David, Siegel, Erin, Jump, Helen, Fulp, William, Springett, Gregory, Kim, Richard |
| Předmět: |
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| Zdroj: |
Cancer Chemotherapy & Pharmacology; Sep2015, Vol. 76 Issue 3, p481-487, 7p |
| Abstrakt: |
Purpose: Pasireotide LAR (SOM230 LAR) is a cyclohexapeptide engineered to bind to multiple somatostatin receptor subtypes to mimic the action of naturally occurring somatostatin with higher affinity to these receptors than octreotide and is a potent inhibitor of insulin-like growth factor-1 (IGF-1). Somatostatin receptors and IGF receptors are highly expressed in pancreatic cancer, thereby potentially making it a valuable target. This phase I study evaluated safety, tolerability and preliminary tumor response of pasireotide LAR in combination with gemcitabine in locally advanced or metastatic pancreatic cancer. Methods: Patients with previously untreated metastatic pancreatic cancer were included. A 3 + 3 dose-escalation design was used. Patients received gemcitabine on days 1, 8 and 15 and pasireotide LAR IM monthly in a 28-day cycle. Two dose levels of pasireotide LAR were planned: 40 mg IM and 60 mg. Cohort was expanded by ten more patients at the highest tested dose to further assess the safety and efficacy. Results: Twenty patients were consented on this trial, and 16 patients were evaluable for safety and efficacy. No dose-limiting toxicities were observed. Two out sixteen patients (12 %) had partial response, and nine of sixteen (56 %) had stable disease as best response. Median progression-free survival was 4.1 months (range 1-16 months), and median overall survival was 6.9 months (range 1-25 months). Most common grade 3 or 4 toxicities were hyperglycemia ( n = 5), hyperbilirubinemia ( n = 1) and thrombocytopenia ( n = 2). Median baseline IGF-1 level was lower in patients with stable disease than in those with progressive disease (63 vs 71 ng/ml). Conclusion: Pasireotide in combination with gemcitabine was well tolerated with disease control rate of 68 %. Larger trials are needed in the future to establish its efficacy in the treatment of pancreatic cancer. Clinical trial: NCT01385956. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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