Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer

Gary Altwerger, Esther B. Florsheim, Gulden Menderes, Jonathan Black, Carlton Schwab, Gregory M. Gressel, Wendelin K. Nelson, Nina Carusillo, Terri Passante, Gloria Huang, Babak Litkouhi, Masoud Azodi, Dan Arin Silasi, Alessandro Santin, Peter E. Schwartz, Elena S. Ratner

Research output: Contribution to journalArticle

Abstract

Purpose: Hypersensitivity reactions (HSRs) to chemotherapy is an ongoing issue in cancer treatments. Strategies to induce tolerance and maximize chemotherapy efficacy include desensitization protocols. The precise impact of these protocols, however, in the long-term treatments remains unclear. We aim to compare overall survival (OS) in hypersensitive patients treated with carboplatin desensitization to patients without hypersensitivity reactions. We also sought to identify new risk factors for HSRs and reconfirm that the DNA repair enzyme, germline BRCA1/2 (gBRCA1/2), is a risk factor for hypersensitivity. Experimental design: Retrospective study in patients with ovarian cancer tested for gBRCA1/2 mutations who received more than six infusions of carboplatin from August 2005 to November 2016. Two-sided Fisher exact, Student’s t test and Gehan–Breslow–Wilcoxon test were used for statistical analysis. Univariate and multivariate analyses were completed to identify independent predictors of survival. Statistical significance was set with a two-sided p value of 0.05. Results: Ninety-one patients with gBRCA1/2 testing met inclusion. Forty patients (44%) were gBRCA1/2-deficient and 51 (56%) were gBRCA1/2-proficient. Patients with gBRCA1/2 deficiencies had a higher likelihood of developing carboplatin hypersensitivity, HR 6.433 (95% CI: 1.868–22.149). None of the patients with carboplatin hypersensitivity were given PARP inhibitors prior to the development of HSRs. The patients with recurrent advanced stage (III–IV) ovarian cancer had a higher likelihood of developing carboplatin hypersensitivity, HR 4.783 (1.008–22.689). Moreover, we found that hypersensitive patients who underwent carboplatin desensitization had a 48-month longer OS than patients without hypersensitivity to carboplatin not undergoing carboplatin desensitization (p = 0.0094). A subgroup analysis indicated that gBRCA1/2-proficient hypersensitive patients undergoing carboplatin desensitization had a 43-month longer OS than gBRCA1/2-proficient patients without HSRs (p = 0.034). Conclusions: We confirmed that gBRCA1/2 deficiency and advanced stage are independent risk factors for development of carboplatin hypersensitivity in ovarian cancer patients. Our study also shows improved OS in hypersensitive patients receiving CD compared to non-hypersensitive patients, independent of gBRCA1/2.

Original languageEnglish (US)
JournalJournal of Cancer Research and Clinical Oncology
DOIs
StateAccepted/In press - Jan 1 2018

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Carboplatin
Ovarian Neoplasms
Hypersensitivity
Survival
DNA Repair Enzymes
Drug Therapy

Keywords

  • BRCA
  • Carboplatin desensitization
  • Carboplatin hypersensitivity
  • DNA damage
  • Ovarian cancer
  • Overall survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer. / Altwerger, Gary; Florsheim, Esther B.; Menderes, Gulden; Black, Jonathan; Schwab, Carlton; Gressel, Gregory M.; Nelson, Wendelin K.; Carusillo, Nina; Passante, Terri; Huang, Gloria; Litkouhi, Babak; Azodi, Masoud; Silasi, Dan Arin; Santin, Alessandro; Schwartz, Peter E.; Ratner, Elena S.

In: Journal of Cancer Research and Clinical Oncology, 01.01.2018.

Research output: Contribution to journalArticle

Altwerger, G, Florsheim, EB, Menderes, G, Black, J, Schwab, C, Gressel, GM, Nelson, WK, Carusillo, N, Passante, T, Huang, G, Litkouhi, B, Azodi, M, Silasi, DA, Santin, A, Schwartz, PE & Ratner, ES 2018, 'Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer', Journal of Cancer Research and Clinical Oncology. https://doi.org/10.1007/s00432-018-2753-y
Altwerger, Gary ; Florsheim, Esther B. ; Menderes, Gulden ; Black, Jonathan ; Schwab, Carlton ; Gressel, Gregory M. ; Nelson, Wendelin K. ; Carusillo, Nina ; Passante, Terri ; Huang, Gloria ; Litkouhi, Babak ; Azodi, Masoud ; Silasi, Dan Arin ; Santin, Alessandro ; Schwartz, Peter E. ; Ratner, Elena S. / Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer. In: Journal of Cancer Research and Clinical Oncology. 2018.
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abstract = "Purpose: Hypersensitivity reactions (HSRs) to chemotherapy is an ongoing issue in cancer treatments. Strategies to induce tolerance and maximize chemotherapy efficacy include desensitization protocols. The precise impact of these protocols, however, in the long-term treatments remains unclear. We aim to compare overall survival (OS) in hypersensitive patients treated with carboplatin desensitization to patients without hypersensitivity reactions. We also sought to identify new risk factors for HSRs and reconfirm that the DNA repair enzyme, germline BRCA1/2 (gBRCA1/2), is a risk factor for hypersensitivity. Experimental design: Retrospective study in patients with ovarian cancer tested for gBRCA1/2 mutations who received more than six infusions of carboplatin from August 2005 to November 2016. Two-sided Fisher exact, Student’s t test and Gehan–Breslow–Wilcoxon test were used for statistical analysis. Univariate and multivariate analyses were completed to identify independent predictors of survival. Statistical significance was set with a two-sided p value of 0.05. Results: Ninety-one patients with gBRCA1/2 testing met inclusion. Forty patients (44{\%}) were gBRCA1/2-deficient and 51 (56{\%}) were gBRCA1/2-proficient. Patients with gBRCA1/2 deficiencies had a higher likelihood of developing carboplatin hypersensitivity, HR 6.433 (95{\%} CI: 1.868–22.149). None of the patients with carboplatin hypersensitivity were given PARP inhibitors prior to the development of HSRs. The patients with recurrent advanced stage (III–IV) ovarian cancer had a higher likelihood of developing carboplatin hypersensitivity, HR 4.783 (1.008–22.689). Moreover, we found that hypersensitive patients who underwent carboplatin desensitization had a 48-month longer OS than patients without hypersensitivity to carboplatin not undergoing carboplatin desensitization (p = 0.0094). A subgroup analysis indicated that gBRCA1/2-proficient hypersensitive patients undergoing carboplatin desensitization had a 43-month longer OS than gBRCA1/2-proficient patients without HSRs (p = 0.034). Conclusions: We confirmed that gBRCA1/2 deficiency and advanced stage are independent risk factors for development of carboplatin hypersensitivity in ovarian cancer patients. Our study also shows improved OS in hypersensitive patients receiving CD compared to non-hypersensitive patients, independent of gBRCA1/2.",
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author = "Gary Altwerger and Florsheim, {Esther B.} and Gulden Menderes and Jonathan Black and Carlton Schwab and Gressel, {Gregory M.} and Nelson, {Wendelin K.} and Nina Carusillo and Terri Passante and Gloria Huang and Babak Litkouhi and Masoud Azodi and Silasi, {Dan Arin} and Alessandro Santin and Schwartz, {Peter E.} and Ratner, {Elena S.}",
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T1 - Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer

AU - Altwerger, Gary

AU - Florsheim, Esther B.

AU - Menderes, Gulden

AU - Black, Jonathan

AU - Schwab, Carlton

AU - Gressel, Gregory M.

AU - Nelson, Wendelin K.

AU - Carusillo, Nina

AU - Passante, Terri

AU - Huang, Gloria

AU - Litkouhi, Babak

AU - Azodi, Masoud

AU - Silasi, Dan Arin

AU - Santin, Alessandro

AU - Schwartz, Peter E.

AU - Ratner, Elena S.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: Hypersensitivity reactions (HSRs) to chemotherapy is an ongoing issue in cancer treatments. Strategies to induce tolerance and maximize chemotherapy efficacy include desensitization protocols. The precise impact of these protocols, however, in the long-term treatments remains unclear. We aim to compare overall survival (OS) in hypersensitive patients treated with carboplatin desensitization to patients without hypersensitivity reactions. We also sought to identify new risk factors for HSRs and reconfirm that the DNA repair enzyme, germline BRCA1/2 (gBRCA1/2), is a risk factor for hypersensitivity. Experimental design: Retrospective study in patients with ovarian cancer tested for gBRCA1/2 mutations who received more than six infusions of carboplatin from August 2005 to November 2016. Two-sided Fisher exact, Student’s t test and Gehan–Breslow–Wilcoxon test were used for statistical analysis. Univariate and multivariate analyses were completed to identify independent predictors of survival. Statistical significance was set with a two-sided p value of 0.05. Results: Ninety-one patients with gBRCA1/2 testing met inclusion. Forty patients (44%) were gBRCA1/2-deficient and 51 (56%) were gBRCA1/2-proficient. Patients with gBRCA1/2 deficiencies had a higher likelihood of developing carboplatin hypersensitivity, HR 6.433 (95% CI: 1.868–22.149). None of the patients with carboplatin hypersensitivity were given PARP inhibitors prior to the development of HSRs. The patients with recurrent advanced stage (III–IV) ovarian cancer had a higher likelihood of developing carboplatin hypersensitivity, HR 4.783 (1.008–22.689). Moreover, we found that hypersensitive patients who underwent carboplatin desensitization had a 48-month longer OS than patients without hypersensitivity to carboplatin not undergoing carboplatin desensitization (p = 0.0094). A subgroup analysis indicated that gBRCA1/2-proficient hypersensitive patients undergoing carboplatin desensitization had a 43-month longer OS than gBRCA1/2-proficient patients without HSRs (p = 0.034). Conclusions: We confirmed that gBRCA1/2 deficiency and advanced stage are independent risk factors for development of carboplatin hypersensitivity in ovarian cancer patients. Our study also shows improved OS in hypersensitive patients receiving CD compared to non-hypersensitive patients, independent of gBRCA1/2.

AB - Purpose: Hypersensitivity reactions (HSRs) to chemotherapy is an ongoing issue in cancer treatments. Strategies to induce tolerance and maximize chemotherapy efficacy include desensitization protocols. The precise impact of these protocols, however, in the long-term treatments remains unclear. We aim to compare overall survival (OS) in hypersensitive patients treated with carboplatin desensitization to patients without hypersensitivity reactions. We also sought to identify new risk factors for HSRs and reconfirm that the DNA repair enzyme, germline BRCA1/2 (gBRCA1/2), is a risk factor for hypersensitivity. Experimental design: Retrospective study in patients with ovarian cancer tested for gBRCA1/2 mutations who received more than six infusions of carboplatin from August 2005 to November 2016. Two-sided Fisher exact, Student’s t test and Gehan–Breslow–Wilcoxon test were used for statistical analysis. Univariate and multivariate analyses were completed to identify independent predictors of survival. Statistical significance was set with a two-sided p value of 0.05. Results: Ninety-one patients with gBRCA1/2 testing met inclusion. Forty patients (44%) were gBRCA1/2-deficient and 51 (56%) were gBRCA1/2-proficient. Patients with gBRCA1/2 deficiencies had a higher likelihood of developing carboplatin hypersensitivity, HR 6.433 (95% CI: 1.868–22.149). None of the patients with carboplatin hypersensitivity were given PARP inhibitors prior to the development of HSRs. The patients with recurrent advanced stage (III–IV) ovarian cancer had a higher likelihood of developing carboplatin hypersensitivity, HR 4.783 (1.008–22.689). Moreover, we found that hypersensitive patients who underwent carboplatin desensitization had a 48-month longer OS than patients without hypersensitivity to carboplatin not undergoing carboplatin desensitization (p = 0.0094). A subgroup analysis indicated that gBRCA1/2-proficient hypersensitive patients undergoing carboplatin desensitization had a 43-month longer OS than gBRCA1/2-proficient patients without HSRs (p = 0.034). Conclusions: We confirmed that gBRCA1/2 deficiency and advanced stage are independent risk factors for development of carboplatin hypersensitivity in ovarian cancer patients. Our study also shows improved OS in hypersensitive patients receiving CD compared to non-hypersensitive patients, independent of gBRCA1/2.

KW - BRCA

KW - Carboplatin desensitization

KW - Carboplatin hypersensitivity

KW - DNA damage

KW - Ovarian cancer

KW - Overall survival

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