- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00161174
Cardiovascular Morbidity in Testicular Cancer Survivors: Study of Risk Factors and Assessment of Pharmacogenomic Determinants of Toxicity
Cardiovascular Morbidity in Testicular Cancer Survivors: Study of Risk Factors and Assessment of Pharmacogenomic Determinants of Toxicity. (KWF RUG 2004-3157)
BACKGROUND:
Evidence has emerged that patients cured with cisplatin-bleomycin chemotherapy from disseminated testicular cancer (TC) develop a large number of cardiovascular risk factors (CRF) several years later. Recently, we observed an increased incidence of cardiac events 10-20 years after chemotherapy, possibly as a result of increased occurrence of CRF. Additional cardiovascular damage was observed after treatment: disturbed diastolic function of the left ventricle, microalbuminuria and increased endothelial damage parameters. Furthermore, a metabolic syndrome (syndrome X) with insulin-resistance, dyslipidemia, hypertension and endothelial damage was found in about one third of our cured patients. The investigators hypothesize that endothelial damage and metabolic changes caused by the bleomycin and cisplatin chemotherapy are the main causes for the observed increase in cardiovascular disease in these young cancer survivors. Genetic susceptibility may be an important determinant of individual risk of toxicity in individual patients.
PURPOSE:
- To identify risk factors for cardiovascular disease (CVD) following testicular cancer.
- To obtain insight into the pathway(s) of CVD development, by examining whether clinical CVD following testicular cancer is associated with a preceding unfavorable cardiovascular risk factor profile and/or with treatment-related factors.
- To investigate genetic polymorphisms in pathogenetically important pathways that are potentially involved in the development of treatment related cardiovascular morbidity following testicular cancer.
PATIENTS AND METHODS:
Patients with non-seminomatous testicular cancer who have been uniformly treated with orchidectomy and cisplatin-bleomycin combination chemotherapy at the University Hospital Groningen, The Netherlands, since 1977 but before 2000 are eligible. 380 patients with non-seminomatous testicular cancer fulfill these criteria. A close routine follow-up of these patients after treatment has been done at the University Hospital Groningen. Clinical characteristics of these patients, treatment details including outcome and long-term follow-up are being registered systematically. From all patients who agree to participate assessment of their cardiovascular risk factors and the presence of subclinical cardiovascular damage will be performed by means of several measurement techniques. Also genomic DNA will be collected for studies on polymorphisms in pathogenetically important pathways. For the total cohort of patients several different late effects phenotypes of cardiovascular damage and cardiovascular risk factor patterns will be derived from the available data. These toxicity phenotypes will be used to select cases and controls from the total cohort to test candidate genetic polymorphisms on their association with occurrence of toxicity. The association of the different genetic polymorphisms with the toxicity phenotype will be estimated by comparing cases with different toxicity phenotypes with controls without that phenotype.
POSSIBLE RESULTS This research will provide insight into the pathogenesis of cardiovascular disease after treatment for testicular cancer. The main outcome will be the possibility to select individually those patients who are likely to have an increased risk to encounter specific cardiovascular toxicity during or after chemotherapy treatment for TC. This will provide opportunities for the tailoring of potential toxic treatment and/or guide primary and secondary prevention strategies for serious side effects of chemotherapy treatment.
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Groningen, Netherlands, 9713 GZ
- University Medical Centre Groningen
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Patients with non-seminomatous testicular cancer
- Have been uniformly treated with orchidectomy and cisplatin-bleomycin combination chemotherapy at the University Hospital Groningen, The Netherlands, since 1977 but before 01-01-2000 are eligible.
Exclusion Criteria:
- N/A
Study Plan
How is the study designed?
Design Details
Collaborators and Investigators
Collaborators
Investigators
- Study Director: Elisabeth G.E. de Vries, MD, PhD, University Medical Center Groningen
Publications and helpful links
General Publications
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- Gietema JA, de Vries EG, Sleijfer DT. Increased incidence of cardiovascular risk factors in cured testicular cancer patients. J Clin Oncol. 1992 Oct;10(10):1652. No abstract available.
- Boyer M, Raghavan D. Toxicity of treatment of germ cell tumors. Semin Oncol. 1992 Apr;19(2):128-42.
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- Berger CC, Bokemeyer C, Schneider M, Kuczyk MA, Schmoll HJ. Secondary Raynaud's phenomenon and other late vascular complications following chemotherapy for testicular cancer. Eur J Cancer. 1995 Dec;31A(13-14):2229-38. doi: 10.1016/0959-8049(95)00460-2.
- Meinardi MT, Gietema JA, van der Graaf WT, van Veldhuisen DJ, Runne MA, Sluiter WJ, de Vries EG, Willemse PB, Mulder NH, van den Berg MP, Koops HS, Sleijfer DT. Cardiovascular morbidity in long-term survivors of metastatic testicular cancer. J Clin Oncol. 2000 Apr;18(8):1725-32. doi: 10.1200/JCO.2000.18.8.1725.
- Meinardi MT, Gietema JA, Van der Graaf WTA et al. Long-term vascular and metabolic sequelae of chemotherapy for metastatic testicular cancer. A comparison with long-term survivors of stage I disease. PROC ASCO 2000; 19: 331a.
- Huddart RA, Norman A, Shahidi M, Horwich A, Coward D, Nicholls J, Dearnaley DP. Cardiovascular disease as a long-term complication of treatment for testicular cancer. J Clin Oncol. 2003 Apr 15;21(8):1513-23. doi: 10.1200/JCO.2003.04.173.
- Travis LB, Curtis RE, Storm H, Hall P, Holowaty E, Van Leeuwen FE, Kohler BA, Pukkala E, Lynch CF, Andersson M, Bergfeldt K, Clarke EA, Wiklund T, Stoter G, Gospodarowicz M, Sturgeon J, Fraumeni JF Jr, Boice JD Jr. Risk of second malignant neoplasms among long-term survivors of testicular cancer. J Natl Cancer Inst. 1997 Oct 1;89(19):1429-39. doi: 10.1093/jnci/89.19.1429.
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Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- KWF RUG 2004-3157
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