Lang A-S, Mounier M, Roques M, Chretien M L, Boulin M
Pharmacy Department, University Hospital, Dijon, France.
Hematological Malignancies Registry, Burgundy University, Dijon, France.
J Clin Pharm Ther. 2015 Aug;40(4):391-7. doi: 10.1111/jcpt.12273. Epub 2015 Apr 10.
Since their introduction, tyrosine kinase inhibitors (TKIs) have been increasingly used in clinical practice. We describe the prescribing and the clinical and biological consequences of two such inhibitors, imatinib and erlotinib, in patients with chronic myeloid leukaemia (CML) in a practice setting over a period of more than 10 years.
All patients who received at least one TKI for chronic phase CML between 2001 and 2012 in our university hospital were included in the study.
Of the 139 patients, with a median age of 57 years, who were surveyed, imatinib and nilotinib were prescribed as the first TKI in 131 (94%) and 8 (6%) patients, respectively. With a median follow-up of 6 years, 342 treatment modifications were observed: 113 (33%) increased doses, 109 (32%) decreased doses, 89 (26%) TKI changes, 14 (4%) definitive discontinuations, 13 (4%) temporary discontinuations and 4 (1%) additions of IFN-α. The main reasons for the 342 treatment modifications were adverse events (n = 112, 33%), long-term optimal response (n = 58, 17%) and failure (n = 57, 17%). Eighty-five (61%), 31 (22%), 18 (13%) and 5 (4%) patients had no, 1, 2 and 3 TKI changes, respectively. Imatinib was the most prescribed TKI (75%). Adverse events resulting in treatment modifications occurred in 18% of patients for imatinib, 49% for nilotinib and 41% for dasatinib (P < 0·001). Median time to TKI change whatever the reason was >50 months (not achieved) for imatinib, 22 months for nilotinib and 27 months for dasatinib (log-rank test, P < 0·001).
Imatinib was the most prescribed TKI both in the first and in subsequent therapeutic lines for chronic phase CML. Our study showed a very good efficacy-safety profile for imatinib at a median follow-up of 6 years in an unselected French population.
自酪氨酸激酶抑制剂（TKIs）问世以来，其在临床实践中的应用日益广泛。我们描述了在超过10年的实际应用中，两种此类抑制剂伊马替尼和厄洛替尼在慢性髓性白血病（CML）患者中的处方情况以及临床和生物学后果。
纳入2001年至2012年期间在我们大学医院接受至少一种TKI治疗慢性期CML的所有患者。
在接受调查的139例患者中，中位年龄为57岁，分别有131例（94%）和8例（6%）患者将伊马替尼和尼洛替尼作为首个TKI处方。中位随访6年，观察到342次治疗调整：113次（33%）增加剂量，109次（32%）减少剂量，89次（26%）更换TKI，14次（4%）最终停药，13次（'4%）暂时停药，4次（1%）加用干扰素-α。342次治疗调整的主要原因是不良事件（n = 112，33%）、长期最佳反应（n = 58，17%）和治疗失败（n = 57，17%）。分别有85例（61%）、31例（22%）、18例（13%）和5例（4%）患者未更换、更换1次、2次和3次TKI。伊马替尼是处方最多的TKI（75%）。因不良事件导致治疗调整的患者中，伊马替尼为18%，尼洛替尼为49%，达沙替尼为41%（P < 0·001）。无论何种原因，伊马替尼更换TKI的中位时间>50个月（未达到），尼洛替尼为22个月，达沙替尼为27个月（对数秩检验，P < 0·001）。
在慢性期CML的一线及后续治疗中，伊马替尼都是处方最多的TKI。我们的研究表明，在未选择的法国人群中，中位随访6年时，伊马替尼具有非常良好的疗效-安全性。
