Phase I dose-escalation study of pasireotide LAR in patients with advanced neuroendocrine tumors
| Autor: | Jennifer A. Chan, Alexandria T. Phan, Guoxiang Shen, Jonathan R. Strosberg, Edward M. Wolin, Gareth Hughes, Jerry M. Huang, Michelle Hudson |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty business.industry Somatostatin receptor Octreotide Neuroendocrine tumors medicine.disease Lanreotide Primary tumor Pasireotide chemistry.chemical_compound Tolerability chemistry Pharmacokinetics Internal medicine medicine business Nuclear medicine medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 31:e15126-e15126 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2013.31.15_suppl.e15126 |
| Popis: | e15126 Background: Somastatin analogs (SSA), including octreotide and lanreotide, bind predominantly to somatostatin receptor (SSTR) 2 and form the foundation of treatment for symptomatic neuroendocrine tumors (NET). Pasireotide, a novel SSA with a broad binding affinity (SSTR 1-3 and 5), is being explored for treatment of NET. A phase 1 dose-escalation study (NCT01364415) of pasireotide long-acting release (LAR; starting dose of 80 mg) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and to characterize safety, tolerability, pharmacokinetics, and efficacy in pts with advanced NET. Methods: Pts with advanced, well- or moderately differentiated NET received pasireotide LAR beginning at a dose of 80 mg q28d. Successive cohorts will receive doses (up to 220 mg) guided by a Bayesian logistic regression model until MTD/RP2D is reached. Results: To date, 15 pts have been treated at 80 mg (n=6) and 120 mg (n=9). Median age is 59 (44-76) years. Primary tumor sites include small intestine (40%), pancreas (20%), and lung (13.3%). All pts received prior antineoplastic therapy; 93% received prior SSA. Median number of cycles of pasireotide was 6.68 (2-14) (1 cycle=28 days). 10 (67%) pts remain on treatment: 3 on 80 mg and 7 on 120 mg. 5 (33%) have discontinued (disease progression, 2 pts; withdrew consent, 2 pts; adverse event [AE], 1 pt). Median plasma concentrations of pasireotide increased with dose. No dose-limiting toxicities have been reported. Most frequent AEs were similar in both dose groups and included hyperglycemia (87%), diarrhea (53%), abdominal pain (47%), nausea (40%), anemia (33%), and fatigue (33%). Most AEs were mild/moderate. 2 pts (1 in each group) had grade 3 hyperglycemia. 4 (27%) and 2 (13%) pts had HbA1C increase from |
| Databáze: | OpenAIRE |
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