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In Reply:

Departments of Medical Oncology, Vascular Medicine, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands

Recent reports on the health status of testicular cancer survivors indicate that approximately 20% to 50% will develop hypertension as late adverse effect some time after cisplatin combination chemotherapy.^1,2 The mechanism of this increase in blood pressure is not well understood but probably related to the damaging effect of cisplatin on endothelial cells. Since it is conceivable that the chemotherapy-induced damage finds its origin during the 12 weeks of standard bleomycin, etoposide, and cisplatin chemotherapy, we investigated acute changes in cardiovascular risk factors and cardiovascular structure and function. Results demonstrated increased plasma levels of von Willebrand factor and increased intima-media thickness of the carotid artery. As noted by Kohli and Kohli, this was accompanied by a significant decrease in 24-hour blood pressure. Blood pressure was measured at median 36 days (range, 11 days to 100 days) after completion of chemotherapy. The median drop in 24-hour blood pressure was 5 to 6 mmHg for both systolic and diastolic blood pressure. None of the patients had signs or symptoms indicating hypotension.

The mechanism of this decrease in 24-hour blood pressure is unclear. It may be normalization of a blood pressure, initially elevated before start of chemotherapy due to disease and treatment related physical and psychological stress as suggested by Sagstuen et al.¹

The suggestion of Kohli and Kohli that the observed decrease in 24-hour blood pressure is a sign of neurotoxicity with impaired autonomic function is an interesting one. We measured Baroreflex sensibility (BRS) at the same time points as the measurement of 24-hour blood pressure. However, the BRS, which can be considered as indicator of autonomic function, did not significantly decrease as a result of cisplatin combination chemotherapy. Furthermore, no relation was found between the change in BRS and the change in 24-hour blood pressure. Most data on the development of hypertension as late adverse effect of cisplatin combination chemotherapy suggest endothelial activation and damage as important contributing factor. Nevertheless a neurotoxic effect of cisplatin may also contribute to this effect.

Recent preclinical data in a rat model of cisplatin-induced neurotoxicity suggest that this neurotoxicity is associated with cisplatin induced damage of endothelial cells of the vasa nervorum. This observed damage of the vasa nervorum caused by cisplatin could be reversed or prevented by administering vascular endothelial growth factor.³ Therefore, the vascular endothelial growth factor pathway may also be involved in development of blood pressure changes after cisplatin combination chemotherapy, such as bleomycin, etoposide, and cisplatin for testicular cancer.

As we know that a substantial part of the patients will develop hypertension with prolonged follow-up, additional follow-up will show whether patients with initial decrease in blood pressure will be prone to the development of hypertension. More research is needed to determine the underlying mechanism(s) of decrease in blood pressure and the possible association with the long-term development of hypertension and other cardiovascular risk factors.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Sagstuen H, Aass N, Fossa SD, et al: Blood pressure and body mass index in long-term survivors of testicular cancer. J Clin Oncol 23:4980-4990, 2005[Abstract/Free Full Text]

2. Nuver J, Smit AJ, Wolffenbuttel BH, et al: The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer. J Clin Oncol 23:3718-3725, 2005[Abstract/Free Full Text]

3. Kirchmair R, Walter DH, Masaaki I, et al: Antiangiogenesis mediates cisplatin-induced peripheral neuropathy: Attenuation or reversal by local vascular endothelial growth factor gene therapy without augmenting tumor growth. Circulation 111:2662-2670, 2005[Abstract/Free Full Text]

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Related Correspondence

• Acute Chemotherapy-Induced Cardiovascular Changes in Patients With Testicular Cancer: Are There Implications for Blood Pressure Management in Patients Receiving Chemotherapy?
  Sadhna Kohli and Manish Kohli
  JCO 2006 24: 2399 [Full Text]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by de Haas, E. C. Articles by Gietema, J. A. Search for Related Content PubMed Articles by de Haas, E. C. Articles by Gietema, J. A. Related Articles Related Correspondence Social Bookmarking                            What's this?