Development of Chronic Myeloid Leukaemia in Patients Treated with Anti-VEGF Therapies for Clear Cell Renal Cell Cancer

ABSTRACT

Tyrosine kinase inhibitors are novel therapies targeting specific cellular signalling pathways. Sunitinib and sorafenib primarily block tyrosine kinase receptors involved in the progression of many tumours, including clear cell renal cell cancer (ccRCC). Although developed to target selected receptors, it is becoming apparent that they inhibit other kinases; this may result in the development of unexpected side effects. This is potentially dangerous as kinases on noncancerous cells are also inhibited. TKI off-target effects contributing to cardiotoxicity, hypothyroidism, hypertension, fatigue, hair depigmentation, hand–foot syndrome and gastrointestinal perforation have been described. We report three patients (3/412) treated with sunitinib and sorafenib who developed chronic myeloid leukaemia (CML) during treatment for ccRCC, proposing a molecular mechanism of tyrosine kinase inhibitors action on bone marrow cells that might be co-responsible for CML development.

KEYWORDS:

• clear cell renal cell
• CML
• RCC
• renal cell cancer
• sorafenib
• sunitinib
• tyrosine kinase carcinoma

Financial & competing interests disclosure

C Szczylik received consulting and lecture honoraria from Pfizer, Bayer HealthCare, Astellas, GlaxoSmithKline and Novartis. AM Czarnecka received lecture honoraria from Pfizer, GlaxoSmithKline, Novartis, Merck, Roche, Vipharm and Hospira. S Oborska and P Rzepecki indicate no potential conflict of interest. All authors declare no other potential conflict of interests. This work was supported by the Military Institute of Medicine statutory founding. Treatment cost was covered by Polish National Health Fund. In development of molecular model CS and AMC have been supported by the Foundation for Polish Science (FNP) TEAM grant no. TEAM/2010–6/8. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Ethical & informed consent disclosure

The manuscript has been prepared after obtaining OS from all patients. All patients have died prior to manuscript preparation. No sensitive personal data of the patient has been used in the manuscript. The authors state that they have obtained verbal and written informed consent from the patient/patients’ relatives for the inclusion of their medical and treatment history within this case report.