A retrospective analysis of the effect of platinum hypersensitivity reactions on overall survival in patients with epithelial ovarian cancer
Young, Jonathan Richard
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Objective: Platinum-based compounds are frequently used as chemotherapeutic agents in the treatment of epithelial ovarian cancer. Due to the frequency of platinum hypersensitivity reactions observed among these patients, the important question arises as to how the subset of patients that experience a hypersensitivity reaction fare in terms of overall survival compared to patients that do not. In matching the prognostic factors of those patients that have experienced a platinum hypersensitivity reaction to those patients that have not, this retrospective analysis serves to investigate the relationship between platinum hypersensitivity reactions and overall survival. Methods: This is a retrospective analysis of patient data extracted from Massachusetts General Hospital's LMR patient database. The primary end-point was overall survival for patients who experienced a platinum-induced hypersensitivity reaction. A random sample of patients with the primary diagnosis of epithelial ovarian cancer that died between the years of 2002 and 2011 and were treated with platinum-based regimen (carboplatin, cisplatin, or oxaliplatin) were included in the analysis. Patients were then classified into 2 groups, those that developed platinum hypersensitivity, and those that did not (controls). Subjects were matched on a number of prognostic factors: age ±5 years, tumor grade, tumor histology, volume of residual disease post cytoreductive surgery (optimal or sub-optimal), and number of platinum cycles received. Both the platinum allergy group and the control group were only included in the analysis if they received both primary cytoreductive surgery and a platinum-based first line of chemotherapy. Statistical analysis included matched analysis by stratified Cox's Regression and representation of Overall Survival probability curves. Results: Thirty-one patients diagnosed from February 1992 through October 2008 were included in this analysis. The age range at the time of diagnosis was from 42.0 to 77.0 years of age, with a median age of 55.9 years. Of the thirty-one patients analyzed that had platinum hypersensitivity reactions, the tumor histologies were noted to be either serous (N=29), endometrioid (N=1), or mixed (N=1). Tumor grade ranged from the most differentiated grade 1 (N=1) to grade 3 (poorly differentiated), however the majority of the patients were grade 3 (N=29). Tumor stage ranged from IC to stage IV, with the majority of the patients being Stage IIIC (N=26). The volume of residual disease following primary cytoreductive surgery was deemed as either optimal (less than 1 cm of residual disease) or suboptimal (greater than 1 em of residual disease). Most of the patients were optimally surgically debulked (N=26). The number of total platinum cycles received ranged from 6 cycles to 28 cycles, with the median number of cycles being 15.7 for the platinum allergy patients and 12.3 for the controls. In analyzing the overall survival data, the platinum allergy group had a median overall survival period of 68.7 (95% CI: 52.30-75.47) months from their date of diagnosis. The control group had a median overall survival period of 35.3 (95% CI: 30.77-38.40) months. The Hazards Ratio (Allergic Patients to Controls) by Matched Analysis using Stratified Cox's Regression was 0.24 with (p=0.0017). Conclusions: In this retrospective analysis, there appears to be a strong correlation between the platinum allergy patients experiencing a greater than double period of overall survival than the control group (Median ST; PA: 68.7 months, C: 35.3 months). Although the sample size in this analysis is relatively small, the correlation between a platinum hypersensitivity reaction and a significant increase in overall survival warrants further exploration.
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