A phase 2 trial of personalized cytotoxic therapy based on tumor immunohistochemistry in previously treated metastatic pancreatic cancer patients

Ramesh K. Ramanathan, Glen J. Weiss, Richard G Posner, N. V. Rajeshkumar, Gayle Jameson, Meraj Aziz, Antje Hoering, Vanessa Bolejack, Anirban Maitra, Monica Fulk, Edward C. Stites, William S. Hlavacek, Zoran Gatalica, Joanne Xiu, Manuel Hidalgo, Daniel D. Von Hoff, Michael T. Barrett

Research output: Contribution to journalArticle

Abstract

Background: The choice of a regimen in metastatic pancreatic cancer patients following progression on 1st line therapy is empiric and outcomes are unsatisfactory. This phase II study was performed to evaluate the efficacy of therapy selected by immunohistochemistry (IHC) in these patients following progression after one or more therapies. Methods: Eligible patients underwent a percutaneous biopsy of a metastatic lesion and treatment selection was determined by IHC. The study required 35 evaluable patients (power of 86%) for detecting a true 1-year survival rate of > 20%. Results: A tumor biopsy was performed in 48 of 49 accrued patients. Study therapy was not given (n=13) either due to insufficient tumor on biopsy (n=8) or due to worsening cancer related symptoms after biopsy (n=5). The demographics of evaluable patients (n=35) are male/female (59%/41%), with age range 34-78 years (median 63 years). Patients had 1-6 prior regimens (median of 2). The most common IHC targets were topoisomerase 1 or 2, thymidylate synthase, excision repair cross-complementation group 1 protein (ERCC1), and osteonectin secreted protein acidic and rich in cysteine (SPARC). Commercially available treatment regimens prescribed included FOLFIRI, FOLFOX, irinotecan, and doxorubicin. The response (RECIST) was 9%, the median survival was 5.6 months (94% CI, 3.8-8.2), and the 1-year survival was 20% (95% CI, 7-33%). Conclusions: In all patients, IHC assays resulted in identification of at least two targets for therapy and a non-cross resistant regimen could be prescribed for therapy with evidence of some benefit. An IHC based treatment strategy is feasible and needs validation in larger studies.

Original languageEnglish (US)
Pages (from-to)925-935
Number of pages11
JournalJournal of Gastrointestinal Oncology
Volume8
Issue number6
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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Pancreatic Neoplasms
Immunohistochemistry
Neoplasms
Biopsy
irinotecan
Therapeutics
Osteonectin
Thymidylate Synthase
Survival
DNA Repair
Doxorubicin
Cysteine
Proteins
Survival Rate
Demography

Keywords

  • Array comparative genomic hybridization (aCGH)
  • Immunohistochemistry (IHC)
  • Molecular profiling (MP)
  • Pancreatic cancer
  • Phase II clinical trial

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

Cite this

A phase 2 trial of personalized cytotoxic therapy based on tumor immunohistochemistry in previously treated metastatic pancreatic cancer patients. / Ramanathan, Ramesh K.; Weiss, Glen J.; Posner, Richard G; Rajeshkumar, N. V.; Jameson, Gayle; Aziz, Meraj; Hoering, Antje; Bolejack, Vanessa; Maitra, Anirban; Fulk, Monica; Stites, Edward C.; Hlavacek, William S.; Gatalica, Zoran; Xiu, Joanne; Hidalgo, Manuel; Von Hoff, Daniel D.; Barrett, Michael T.

In: Journal of Gastrointestinal Oncology, Vol. 8, No. 6, 01.12.2017, p. 925-935.

Research output: Contribution to journalArticle

Ramanathan, RK, Weiss, GJ, Posner, RG, Rajeshkumar, NV, Jameson, G, Aziz, M, Hoering, A, Bolejack, V, Maitra, A, Fulk, M, Stites, EC, Hlavacek, WS, Gatalica, Z, Xiu, J, Hidalgo, M, Von Hoff, DD & Barrett, MT 2017, 'A phase 2 trial of personalized cytotoxic therapy based on tumor immunohistochemistry in previously treated metastatic pancreatic cancer patients', Journal of Gastrointestinal Oncology, vol. 8, no. 6, pp. 925-935. https://doi.org/10.21037/jgo.2017.09.05
Ramanathan, Ramesh K. ; Weiss, Glen J. ; Posner, Richard G ; Rajeshkumar, N. V. ; Jameson, Gayle ; Aziz, Meraj ; Hoering, Antje ; Bolejack, Vanessa ; Maitra, Anirban ; Fulk, Monica ; Stites, Edward C. ; Hlavacek, William S. ; Gatalica, Zoran ; Xiu, Joanne ; Hidalgo, Manuel ; Von Hoff, Daniel D. ; Barrett, Michael T. / A phase 2 trial of personalized cytotoxic therapy based on tumor immunohistochemistry in previously treated metastatic pancreatic cancer patients. In: Journal of Gastrointestinal Oncology. 2017 ; Vol. 8, No. 6. pp. 925-935.
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abstract = "Background: The choice of a regimen in metastatic pancreatic cancer patients following progression on 1st line therapy is empiric and outcomes are unsatisfactory. This phase II study was performed to evaluate the efficacy of therapy selected by immunohistochemistry (IHC) in these patients following progression after one or more therapies. Methods: Eligible patients underwent a percutaneous biopsy of a metastatic lesion and treatment selection was determined by IHC. The study required 35 evaluable patients (power of 86{\%}) for detecting a true 1-year survival rate of > 20{\%}. Results: A tumor biopsy was performed in 48 of 49 accrued patients. Study therapy was not given (n=13) either due to insufficient tumor on biopsy (n=8) or due to worsening cancer related symptoms after biopsy (n=5). The demographics of evaluable patients (n=35) are male/female (59{\%}/41{\%}), with age range 34-78 years (median 63 years). Patients had 1-6 prior regimens (median of 2). The most common IHC targets were topoisomerase 1 or 2, thymidylate synthase, excision repair cross-complementation group 1 protein (ERCC1), and osteonectin secreted protein acidic and rich in cysteine (SPARC). Commercially available treatment regimens prescribed included FOLFIRI, FOLFOX, irinotecan, and doxorubicin. The response (RECIST) was 9{\%}, the median survival was 5.6 months (94{\%} CI, 3.8-8.2), and the 1-year survival was 20{\%} (95{\%} CI, 7-33{\%}). Conclusions: In all patients, IHC assays resulted in identification of at least two targets for therapy and a non-cross resistant regimen could be prescribed for therapy with evidence of some benefit. An IHC based treatment strategy is feasible and needs validation in larger studies.",
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AU - Weiss, Glen J.

AU - Posner, Richard G

AU - Rajeshkumar, N. V.

AU - Jameson, Gayle

AU - Aziz, Meraj

AU - Hoering, Antje

AU - Bolejack, Vanessa

AU - Maitra, Anirban

AU - Fulk, Monica

AU - Stites, Edward C.

AU - Hlavacek, William S.

AU - Gatalica, Zoran

AU - Xiu, Joanne

AU - Hidalgo, Manuel

AU - Von Hoff, Daniel D.

AU - Barrett, Michael T.

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N2 - Background: The choice of a regimen in metastatic pancreatic cancer patients following progression on 1st line therapy is empiric and outcomes are unsatisfactory. This phase II study was performed to evaluate the efficacy of therapy selected by immunohistochemistry (IHC) in these patients following progression after one or more therapies. Methods: Eligible patients underwent a percutaneous biopsy of a metastatic lesion and treatment selection was determined by IHC. The study required 35 evaluable patients (power of 86%) for detecting a true 1-year survival rate of > 20%. Results: A tumor biopsy was performed in 48 of 49 accrued patients. Study therapy was not given (n=13) either due to insufficient tumor on biopsy (n=8) or due to worsening cancer related symptoms after biopsy (n=5). The demographics of evaluable patients (n=35) are male/female (59%/41%), with age range 34-78 years (median 63 years). Patients had 1-6 prior regimens (median of 2). The most common IHC targets were topoisomerase 1 or 2, thymidylate synthase, excision repair cross-complementation group 1 protein (ERCC1), and osteonectin secreted protein acidic and rich in cysteine (SPARC). Commercially available treatment regimens prescribed included FOLFIRI, FOLFOX, irinotecan, and doxorubicin. The response (RECIST) was 9%, the median survival was 5.6 months (94% CI, 3.8-8.2), and the 1-year survival was 20% (95% CI, 7-33%). Conclusions: In all patients, IHC assays resulted in identification of at least two targets for therapy and a non-cross resistant regimen could be prescribed for therapy with evidence of some benefit. An IHC based treatment strategy is feasible and needs validation in larger studies.

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