Tyrosine kinase inhibitor-induced macrocytosis.
BACKGROUND
The tyrosine kinase inhibitors (TKI) sunitinib and imatinib were shown to induce macrocytosis in patients with renal cell cancer (RCC) and gastrointestinal stromal tumors (GIST), presumably through inhibition of the c-KIT dependent signaling pathway of erythroid progenitor cells of the bone marrow.


METHODS
Hematology charts of patients with RCC, breast cancer (BC), GIST, non-small cell lung cancer (NSCLC) and hepatocellular cancer (HCC), receiving single-agent sunitinib, imatinib, sorafenib, erlotinib and BI 2992 (Tovok) at the recommended dose for at least 3 months were reviewed retrospectively for the occurrence of macrocytosis.


RESULTS
Macrocytosis occurred in all patients with RCC and BC treated with sunitinib and in all patients with GIST treated with imatinib. The percentage increase of the mean corpuscular volume (MCV) of peripheral red blood cells (RBC) compared with baseline at 3, 6, 9 and 12 months was 12.4%, 16.8%, 16.6%, 12.7% and 0.7%, 5.6%, 5.9%, 5% with sunitinib and imatinib respectively. The values at 3, 6 and 9 months between both groups were significantly different. Sorafenib, erlotinib and BI 2992 did not induce macrocytosis.


CONCLUSIONS
Sunitinib-induced macrocytosis was not confined to patients with RCC alone but also occurred in patients with BC. Imatinib also induced macrocytosis in patients with GIST but to a significantly lower degree. Because both drugs were used at an effective pharmacodynamic dose inhibiting c-KIT, these data strongly suggest that pathways in addition to c-KIT and not common to both agents are involved in the TKI-induced macrocytosis.
Schallier
D
D
Department of Medical Oncology, Oncologisch Centrum UZ, Brussel, 1090 Brussels, Belgium. denis.schallier@uzbrussel.be
Trullemans
F
F
Fontaine
C
C
Decoster
L
L
De Greve
J
J
D000748:Anemia, Macrocytic / Q000139:chemically induced* / Q000453:epidemiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001549:Benzamides; D001557:Benzenesulfonates / Q000008:administration & dosage; D000069347:Erlotinib Hydrochloride; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000008:administration & dosage; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010879:Piperazines / Q000008:administration & dosage; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D012189:Retrospective Studies; D000077157:Sorafenib; D000077210:Sunitinib; D015996:Survival Rate
D001549:Benzamides; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D011799:Quinazolines; D009536:Niacinamide; D000068877:Imatinib Mesylate; D000077157:Sorafenib; D000069347:Erlotinib Hydrochloride; D019009:Proto-Oncogene Proteins c-kit; D000077210:Sunitinib