Confusion of Therapeutic Approaches
Schlitt et al. in their review article focused on cardiotoxic oncological treatments (1). Adequate management of adverse effects of cardiotoxic treatments ensures optimal results of oncological treatment. In the article by Schlitt et al., an algorithm was proposed for monitoring, prevention, and treatment in the context of cardiotoxicity, including the VEGFR inhibitors sunitinib and sorafenib.
Schmidinger et al. postulated direct cardiotoxicity for sunitinib and sorafenib on the basis of a retrospective analysis (2). However, prospective clinical studies did not confirm this suspicion (Haas et al, ASCO Annual Meeting Proceedings, J Clin Oncol 2012; 30[suppl 18; abstr 4500]; Michel MS et al., ASCO Genitourinary Cancers Symposium, J Clin Oncol 2014; 32[suppl 4; abstr 393]). Rather, the discussion concerns cardiac events as a consequence of uncontrolled, treatment-associated, arterial hypertension, a class-specific adverse drug effect of the VEGFR inhibitors (3). Accordingly, monitoring and regulation of blood pressure in patients taking VEGFR inhibitors are essential in order to prevent secondary cardiac events (4). For cytotoxic drugs, such as doxorubicin, the monitoring measures for identifying cumulative myocardial injury described by Schlitt et al may be adequate, but this approach is not sufficient for VEGFR inhibitors.
In sum, my main criticism of the proposed algorithm is the confusion of curative and palliative treatments, as well as the lack of discrimination between acute, sporadically occurring, and cumulative cardiotoxicity, which as a rule have different underlying pathomechanisms. A blanket recommendation to monitor cardiac function often does not do justice to the individual therapeutic scenario and requires an understanding of the class of substance administered. At least for the use of VEGFR inhibitors there is hardly any rationale for the proposed algorithm; instead, the priority should be to proactively regulate and monitor blood pressure during treatment.
Dr. med. Philipp Ivanyi
PD Dr. med. Viktor Grünwald
Klinik für Hämatologie, Hämostaseologie,
Onkologie und Stammzelltransplantation, MHH Hannover
PD Dr. med. Sandra Steffens
Klinik für Urologie und urologische Onkologie, MHH
Conflict of interest statement
Dr Ivanyi has received consultancy fees (Advisory Board) from Bayer.
PD Dr Grünwald has received consultancy fees (Advisory Board) from Bayer, Novartis, GSK, Pfizer, and Astellas. Delegate fees and travel expenses were covered on his behalf by Novartis, Pfizer, and GSK. He has received lecture honoraria from Novartis, GSK, Pfizer, and Astellas. He has received study funding (third party funding) from Pfizer, Novartis, and GSK.
PD Dr Steffens has received consultancy fees (Advisory Board) from Bayer Healthcare. He has been reimbursed for conference delegate fees and travel expenses from Pfizer, Bayer Healthcare, and GSK.
|1.||Schlitt A, Jordan K, Vordermark D, Schwamborn J, Langer T, Thomssen C: Cardiotoxicity and oncological treatments. Dtsch Arztebl Int 2014; 111: 161–8. VOLLTEXT|
|2.||Schmidinger M, Zielinski CC, Vogl UM, et al.: Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2008; 26: 5204–12. CrossRef MEDLINE|
|3.||Bamias A, Lainakis G, Manios E, et al.: Could rigorous diagnosis and management of hypertension reduce cardiac events in patients with renal cell carcinoma treated with tyrosine kinase inhibitors? J Clin Oncol 2009; 27: 2567–9; author reply 9–70. CrossRef MEDLINE|
|4.||de Jesus-Gonzalez N, Robinson E, Moslehi J, Humphreys BD: Management of antiangiogenic therapy-induced hypertension. Hypertension 2012; 60: 607–15. CrossRef MEDLINE PubMed Central|