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

Authors

Gary Altwerger, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA. gary.altwerger@yale.edu.
Esther B. Florsheim, Department of Immunobiology, Yale University School of Medicine, 333 Cedar Street, FMB307, New Haven, CT, 06520, USA.
Gulden Menderes, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.
Jonathan Black, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.
Carlton Schwab, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.
Gregory M. Gressel, Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Wendelin K. Nelson, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.
Nina Carusillo, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.
Terri Passante, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.
Gloria Huang, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.
Babak Litkouhi, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.
Masoud Azodi, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.
Dan-Arin Silasi, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.
Alessandro Santin, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.
Peter E. Schwartz, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.
Elena S. Ratner, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06520, USA.

Document Type

Article

Publication Title

Journal of cancer research and clinical oncology

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.

First Page

2449

Last Page

2456

DOI

10.1007/s00432-018-2753-y

Publication Date

12-1-2018

Recommended Citation

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.; and Ratner, Elena S., "Impact of carboplatin hypersensitivity and desensitization on patients with recurrent ovarian cancer" (2018). Obstetrics and Gynecology. 128.
https://scholar.bridgeporthospital.org/obgyn/128

Identifier

30255380 (pubmed); PMC11813260 (pmc); 10.1007/s00432-018-2753-y (doi); 10.1007/s00432-018-2753-y (pii)