Browsing by Subject "Cisplatin-based chemotherapy"

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    Clinical and Genome-Wide Analysis of Serum Platinum Levels after Cisplatin-Based Chemotherapy
    (American Association for Cancer Research, 2019-10-01) Trendowski, Matthew R.; El Charif, Omar; Ratain, Mark J.; Monahan, Patrick; Mu, Zepeng; Wheeler, Heather E.; Dinh, Paul C., Jr.; Feldman, Darren R.; Ardeshir-Rouhani-Fard, Shirin; Hamilton, Robert J.; Vaughn, David J.; Fung, Chunkit; Kollmannsberger, Christian; Mushiroda, Taisei; Kubo, Michiaki; Hannigan, Robyn; Strathmann, Frederick; Einhorn, Lawrence H.; Fossa, Sophie D.; Travis, Lois B.; Dolan, M. Eileen; Medicine, School of Medicine
    Purpose: Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1-35 years after CBC and evaluate genetic contributions to these levels. Experimental Design: Eligible TCS given 300 or 400 (±15) mg/m2 cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires and had crude serum platinum levels measured. Associations between serum platinum and various risk factors and toxicities were assessed after fitting a bi-exponential model adjusted for follow-up time and cumulative cisplatin dose. A genome-wide association study (GWAS) was performed using the serum platinum residuals of the dose and time-adjusted model. Results: Serum platinum levels exceeded the reference range for approximately 31 years, with a strong inverse relationship with creatinine clearance at follow-up (age-adjusted p = 2.13×10−3). We observed a significant, positive association between residual platinum values and luteinizing hormone (age-adjusted p=6.58×10−3). Patients with high residual platinum levels experienced greater Raynaud’s phenomenon than those with medium or low levels (age-adjusted ORhigh/low = 1.46; p = 0.04), as well as a higher likelihood of developing tinnitus (age-adjusted ORhigh/low = 1.68, p = 0.07). GWAS identified one single nucleotide polymorphism (SNP) meeting genome-wide significance rs1377817 (p=4.6×10−8, a SNP intronic to MYH14). Conclusions: This study indicates that residual platinum values are correlated with several cisplatin-related toxicities. One genetic variant is associated with these levels.
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    Multi-Institutional Assessment of Adverse Health Outcomes Among North American Testicular Cancer Survivors After Modern Cisplatin-Based Chemotherapy
    (American Society of Clinical Oncology, 2017-04) Fung, Chunkit; Sesso, Howard D.; Williams, Annalynn M.; Kerns, Sarah L.; Monahan, Patrick; Abu Zaid, Mohammad; Feldman, Darren R.; Hamilton, Robert J.; Vaughn, David J.; Beard, Clair J.; Kollmannsberger, Christian K.; Cook, Ryan; Althouse, Sandra; Ardeshir-Rouhani-Fard, Shirin; Lipshultz, Steve E.; Einhorn, Lawrence H.; Fossa, Sophie D.; Travis, Lois B.; Department of Medicine, IU School of Medicine
    Purpose To provide new information on adverse health outcomes (AHOs) in testicular cancer survivors (TCSs) after four cycles of etoposide and cisplatin (EPX4) or three or four cycles of bleomycin, etoposide, cisplatin (BEPX3/BEPX4). Methods Nine hundred fifty-two TCSs > 1 year postchemotherapy underwent physical examination and completed a questionnaire. Multinomial logistic regression estimated AHOs odds ratios (ORs) in relation to age, cumulative cisplatin and/or bleomycin dose, time since chemotherapy, sociodemographic factors, and health behaviors. Results Median age at evaluation was 37 years; median time since chemotherapy was 4.3 years. Chemotherapy consisted largely of BEPX3 (38.2%), EPX4 (30.9%), and BEPX4 (17.9%). None, one to two, three to four, or five or more AHOs were reported by 20.4%, 42.0%, 25.1%, and 12.5% of TCSs, respectively. Median number after EPX4 or BEPX3 was two (range, zero to nine and zero to 11, respectively; P > .05) and two (range, zero to 10) after BEPX4. When comparing individual AHOs for EPX4 versus BEPX3, Raynaud phenomenon (11.6% v 21.4%; P < .01), peripheral neuropathy (29.2% v 21.4%; P = .02), and obesity (25.5% v 33.0%; P = .04) differed. Larger cumulative bleomycin doses (OR, 1.44 per 90,000 IU) were significantly associated with five or more AHOs. Increasing age was a significant risk factor for one to two, three to four, or five or more AHOs versus zero AHOs (OR, 1.22, 1.50, and 1.87 per 5 years, respectively; P < .01); vigorous physical activity was protective (OR, 0.62, 0.51, and 0.41, respectively; P < .05). Significant risk factors for three to four and five or more AHOs included current (OR, 3.05 and 3.73) or former (OR, 1.61 and 1.76) smoking (P < .05). Self-reported health was excellent/very good in 59.9% of TCSs but decreased as AHOs increased (P < .001). Conclusion Numbers of AHOs after EPX4 or BEPX3 appear similar, with median follow-up of 4.3 years. A healthy lifestyle was associated with reduced number of AHOs.