Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach

Allyson J. Ocean, Paul Christos, Joseph A. Sparano, Manish A. Shah, Rhonda K. Yantiss, Jonathan Cheng, Juan Lin, Michael Papetti, Dan Matulich, Felice Schnoll-Sussman, Christen Besanceney-Webler, Jenny Xiang, Maureen Ward, Kaili Temple Dilts, Roger Keresztes, Shannon Holloway, Eric X. Chen, John J. Wright, Maureen E. Lane

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: To determine the effectiveness of bortezomib plus irinotecan and bortezomib alone in patients with advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma. We also sought to explore the effect of these therapeutics on tumor and normal gene expression in vivo. Methods: Forty-one patients with advanced GEJ (89 %) or gastric (11 %) adenocarcinoma received bortezomib (1.3 mg/m2 days 1, 4, 8, 11) plus irinotecan (125 mg/m2 days 1, 8) every 21 days as first line therapy (N=29), or bortezomib alone as second line therapy (N=12). The trial was designed to detect a 40 % response rate for the combination, and 20 % response rate for bortezomib alone. Affymetrix HU133A gene chip arrays were used for gene expression studies. Results: Objective response occurred in 3 of 29 patients (10 %, 95 % confidence intervals [CI] 2 %, 27 %) treated with bortezomib plus irinotecan, and in 1 of 12 patients (8 %, 95 % CI 0 %, 39 %) with bortezomib alone. Due to the limited number of responders, there were no significant correlations with response found in the gene expression profiles of 12 patients whose tumors were sampled before and 24 h after therapy with bortezomib alone (N=2) or the combination (N=10). Conclusions: We conclude that bortezomib is not effective for the treatment of advanced adenocarcinoma of the GEJ or stomach, whether used alone or in combination with irinotecan, in an unselected patient population.

Original languageEnglish (US)
Pages (from-to)542-548
Number of pages7
JournalInvestigational New Drugs
Volume32
Issue number3
DOIs
StatePublished - 2014

Fingerprint

irinotecan
Esophagogastric Junction
Stomach
Adenocarcinoma
Confidence Intervals
Gene Expression
Bortezomib

Keywords

  • Adenocarcinoma
  • Bortezomib
  • Combination therapy
  • Gastroesophageal junction
  • Irinotecan
  • Microarray
  • Proteasome inhibitor

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology
  • Medicine(all)

Cite this

Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach. / Ocean, Allyson J.; Christos, Paul; Sparano, Joseph A.; Shah, Manish A.; Yantiss, Rhonda K.; Cheng, Jonathan; Lin, Juan; Papetti, Michael; Matulich, Dan; Schnoll-Sussman, Felice; Besanceney-Webler, Christen; Xiang, Jenny; Ward, Maureen; Dilts, Kaili Temple; Keresztes, Roger; Holloway, Shannon; Chen, Eric X.; Wright, John J.; Lane, Maureen E.

In: Investigational New Drugs, Vol. 32, No. 3, 2014, p. 542-548.

Research output: Contribution to journalArticle

Ocean, AJ, Christos, P, Sparano, JA, Shah, MA, Yantiss, RK, Cheng, J, Lin, J, Papetti, M, Matulich, D, Schnoll-Sussman, F, Besanceney-Webler, C, Xiang, J, Ward, M, Dilts, KT, Keresztes, R, Holloway, S, Chen, EX, Wright, JJ & Lane, ME 2014, 'Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach', Investigational New Drugs, vol. 32, no. 3, pp. 542-548. https://doi.org/10.1007/s10637-014-0070-0
Ocean, Allyson J. ; Christos, Paul ; Sparano, Joseph A. ; Shah, Manish A. ; Yantiss, Rhonda K. ; Cheng, Jonathan ; Lin, Juan ; Papetti, Michael ; Matulich, Dan ; Schnoll-Sussman, Felice ; Besanceney-Webler, Christen ; Xiang, Jenny ; Ward, Maureen ; Dilts, Kaili Temple ; Keresztes, Roger ; Holloway, Shannon ; Chen, Eric X. ; Wright, John J. ; Lane, Maureen E. / Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach. In: Investigational New Drugs. 2014 ; Vol. 32, No. 3. pp. 542-548.
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abstract = "Purpose: To determine the effectiveness of bortezomib plus irinotecan and bortezomib alone in patients with advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma. We also sought to explore the effect of these therapeutics on tumor and normal gene expression in vivo. Methods: Forty-one patients with advanced GEJ (89 {\%}) or gastric (11 {\%}) adenocarcinoma received bortezomib (1.3 mg/m2 days 1, 4, 8, 11) plus irinotecan (125 mg/m2 days 1, 8) every 21 days as first line therapy (N=29), or bortezomib alone as second line therapy (N=12). The trial was designed to detect a 40 {\%} response rate for the combination, and 20 {\%} response rate for bortezomib alone. Affymetrix HU133A gene chip arrays were used for gene expression studies. Results: Objective response occurred in 3 of 29 patients (10 {\%}, 95 {\%} confidence intervals [CI] 2 {\%}, 27 {\%}) treated with bortezomib plus irinotecan, and in 1 of 12 patients (8 {\%}, 95 {\%} CI 0 {\%}, 39 {\%}) with bortezomib alone. Due to the limited number of responders, there were no significant correlations with response found in the gene expression profiles of 12 patients whose tumors were sampled before and 24 h after therapy with bortezomib alone (N=2) or the combination (N=10). Conclusions: We conclude that bortezomib is not effective for the treatment of advanced adenocarcinoma of the GEJ or stomach, whether used alone or in combination with irinotecan, in an unselected patient population.",
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T1 - Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach

AU - Ocean, Allyson J.

AU - Christos, Paul

AU - Sparano, Joseph A.

AU - Shah, Manish A.

AU - Yantiss, Rhonda K.

AU - Cheng, Jonathan

AU - Lin, Juan

AU - Papetti, Michael

AU - Matulich, Dan

AU - Schnoll-Sussman, Felice

AU - Besanceney-Webler, Christen

AU - Xiang, Jenny

AU - Ward, Maureen

AU - Dilts, Kaili Temple

AU - Keresztes, Roger

AU - Holloway, Shannon

AU - Chen, Eric X.

AU - Wright, John J.

AU - Lane, Maureen E.

PY - 2014

Y1 - 2014

N2 - Purpose: To determine the effectiveness of bortezomib plus irinotecan and bortezomib alone in patients with advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma. We also sought to explore the effect of these therapeutics on tumor and normal gene expression in vivo. Methods: Forty-one patients with advanced GEJ (89 %) or gastric (11 %) adenocarcinoma received bortezomib (1.3 mg/m2 days 1, 4, 8, 11) plus irinotecan (125 mg/m2 days 1, 8) every 21 days as first line therapy (N=29), or bortezomib alone as second line therapy (N=12). The trial was designed to detect a 40 % response rate for the combination, and 20 % response rate for bortezomib alone. Affymetrix HU133A gene chip arrays were used for gene expression studies. Results: Objective response occurred in 3 of 29 patients (10 %, 95 % confidence intervals [CI] 2 %, 27 %) treated with bortezomib plus irinotecan, and in 1 of 12 patients (8 %, 95 % CI 0 %, 39 %) with bortezomib alone. Due to the limited number of responders, there were no significant correlations with response found in the gene expression profiles of 12 patients whose tumors were sampled before and 24 h after therapy with bortezomib alone (N=2) or the combination (N=10). Conclusions: We conclude that bortezomib is not effective for the treatment of advanced adenocarcinoma of the GEJ or stomach, whether used alone or in combination with irinotecan, in an unselected patient population.

AB - Purpose: To determine the effectiveness of bortezomib plus irinotecan and bortezomib alone in patients with advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma. We also sought to explore the effect of these therapeutics on tumor and normal gene expression in vivo. Methods: Forty-one patients with advanced GEJ (89 %) or gastric (11 %) adenocarcinoma received bortezomib (1.3 mg/m2 days 1, 4, 8, 11) plus irinotecan (125 mg/m2 days 1, 8) every 21 days as first line therapy (N=29), or bortezomib alone as second line therapy (N=12). The trial was designed to detect a 40 % response rate for the combination, and 20 % response rate for bortezomib alone. Affymetrix HU133A gene chip arrays were used for gene expression studies. Results: Objective response occurred in 3 of 29 patients (10 %, 95 % confidence intervals [CI] 2 %, 27 %) treated with bortezomib plus irinotecan, and in 1 of 12 patients (8 %, 95 % CI 0 %, 39 %) with bortezomib alone. Due to the limited number of responders, there were no significant correlations with response found in the gene expression profiles of 12 patients whose tumors were sampled before and 24 h after therapy with bortezomib alone (N=2) or the combination (N=10). Conclusions: We conclude that bortezomib is not effective for the treatment of advanced adenocarcinoma of the GEJ or stomach, whether used alone or in combination with irinotecan, in an unselected patient population.

KW - Adenocarcinoma

KW - Bortezomib

KW - Combination therapy

KW - Gastroesophageal junction

KW - Irinotecan

KW - Microarray

KW - Proteasome inhibitor

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