Phase i study of combination of pasireotide LAR + gemcitabine in locally advanced or metastatic pancreatic cancer

Yaman Suleiman, Amit Mahipal, David Shibata, Erin M. Siegel, Helen Jump, William J. Fulp, Gregory M. Springett, Richard Kim

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)481-487
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume76
Issue number3
DOIs
StatePublished - Sep 21 2015

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gemcitabine
Pancreatic Neoplasms
Somatostatin Receptors
Somatomedins
Toxicity
Safety
Disease control
Gilbert Disease
Octreotide
Somatostatin
pasireotide
Tumors
Hyperglycemia
Disease-Free Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Phase i study of combination of pasireotide LAR + gemcitabine in locally advanced or metastatic pancreatic cancer. / Suleiman, Yaman; Mahipal, Amit; Shibata, David; Siegel, Erin M.; Jump, Helen; Fulp, William J.; Springett, Gregory M.; Kim, Richard.

In: Cancer Chemotherapy and Pharmacology, Vol. 76, No. 3, 21.09.2015, p. 481-487.

Research output: Contribution to journalArticle

Suleiman, Yaman ; Mahipal, Amit ; Shibata, David ; Siegel, Erin M. ; Jump, Helen ; Fulp, William J. ; Springett, Gregory M. ; Kim, Richard. / Phase i study of combination of pasireotide LAR + gemcitabine in locally advanced or metastatic pancreatic cancer. In: Cancer Chemotherapy and Pharmacology. 2015 ; Vol. 76, No. 3. pp. 481-487.
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abstract = "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.",
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T1 - Phase i study of combination of pasireotide LAR + gemcitabine in locally advanced or metastatic pancreatic cancer

AU - Suleiman, Yaman

AU - Mahipal, Amit

AU - Shibata, David

AU - Siegel, Erin M.

AU - Jump, Helen

AU - Fulp, William J.

AU - Springett, Gregory M.

AU - Kim, Richard

PY - 2015/9/21

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AB - 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.

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