Tyrosine kinase inhibitors and solid tumours: case report and review of the literature.
Bcr-Abl tyrosine kinase inhibitors (TKIs) such as imatinib or dasatinib produce high cytogenetic response rates in patients with Philadelphia-positive chronic myeloid leukaemia (CML) with a good overall safety profile. Despite a complete molecular response, it is currently recommended to continue these targeted therapies to avoid relapse. The immediate and short-term TKI side effects are well known, but the long-term side effects have not yet been clearly identified. A preclinical study in rats treated with TKI showed a statistically significant increase in benign and malignant renal tumours. The authors report the case of a 61-year-old man with CML treated with imatinib with a good response, and they switched to dasatinib after grade 4 hepatic toxicity. He had received treatment with 400 mg of imatinib per day for 77 days, followed by dasatinib for 133 days. He developed a metastatic carcinoma of unknown origin during TKI therapy. Despite chemotherapy, the patient died 2 months after the diagnosis. Although several cases of solid tumours have been reported during TKI therapy, the link between cancer and TKIs is not yet clear. Imatinib has remarkably improved the prognosis of patients with CML. Monitoring of the long-term safety profile of TKIs is essential due to the prolonged survival of these patients.
Roszkiewicz
F
F
Service d'Hématologie, Centre Hospitalier Universitaire, Amiens, France.
Garidi
R
R
Vaida
I
I
Royer
B
B
Parcelier
A
A
Marolleau
J P
JP
Damaj
G
G
D000284:Administration, Oral; D001549:Benzamides; D002277:Carcinoma / Q000139:chemically induced* / Q000473:pathology; D000069439:Dasatinib; D017809:Fatal Outcome; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D000069439:Dasatinib