The Evaluation of the Efficacy and the Safety of Docetaxel in Korean Breast Cancer Patients: through Post-Authori- zation Survey to Fulfill the Registrative Requirement

Moon, Hanlim; Shim, Jee Yoon; Choi, Yoon Jung; Cheong, Hye Jin; You, Do Ra; Chung, Kab Do; Lee, Yil Seob

Abstract

PURPOSE
Post-authorization survey(PAS) is a useful tool for obtainting wider range of data on the safety and efficacy of new drugs following their approval, as they can detect uncommon, unreported adverse events(AEs), which enables more attention to be directed to the practioners. Especially, the limited number of patients in oncology trial cannot usually give the actual incidence of AEs. METHODS: Since Nov. 1998, when docetaxel gained Korean approval in the treatment of breast cancer, a PAS to investigate its safety profiles has been conducted targeting more than 600 patients over 4 calendar years. RESULTS: Case report forms from 626 out of 646 patients were assessable for safety and 444 for efficacy. The patient characteristics are: mean age, 48.1 years; male/female 4/622; Wt/Ht/BSA 57.9 kg/156.1 cm/1.56 m2 ; stage I-II/III/IV 109 (18.2%)/125 (20.8%)/366(61.0%). In 344 patients, 960 AEs were reported in severity of mild/moderate/severe in 6.7, 40.9 and 51.1 % of cases. From AE results, 36.0% needed dose reduction; 34.3% transient interruption of the cycle; and 1.3% permanent discontinuation of docetaxel. Thirty five serious AEs such as febrile neutropenia, alopecia, diarrhea, abdominal pain and headache were reported in 21 patients. Unexpected AEs such as skin ulcer, discoloration of skin, H. Zoster infection, ulticaria, facial flush, chest pain, hemoptysis, pneumonia, stridor, nasal bleeding, photophobia, haematuria, Cushing's syndrome, hyperglycemia and insomnia were reported regardless of any causal relationship. Factors affecting the development of AEs were age, stage, concomitant medication other than chemotherapeutic agents and the number of cycles treated. The efficacy was evaluable in 444 patients with overall response rate of 36.5% (CR/PR 6.3/30.2%). Factors affecting the efficacy were stage, concommitant medication other than chemotherapeutic agents and the number of treatment cycles. CONCLUSION: This post-authorization survey on the safety and efficacy of docetaxel in breast cancer offers oncology practice in the real world without subject selection as is the case in clinical trials, although it was performed to fulfill the registrative requirement of the Korean health authority with limited data. The efficacy and safety profile of docetaxel in breast cancer was no much different from those reported in clinical trials.