Curcumin's effect in advanced and metastatic breast cancer patients treated with first or second-line docetaxel: A randomized trial

Abstract

Background: In this study, we investigated whether the association of curcumin and docetaxel among advanced and metastatic breast cancer patients in first or second-line treatment potentiated the objective response rate.

Patients/methods: A multicentre, randomized, open label, phase-II study was conducted and included 42 patients from July 2009 to January 2017. The primary endpoint was the objective response rate of the docetaxel-curcumin combination in comparison with docetaxel alone. The secondary endpoints were the assessment of clinical benefit, overall survival, time-to-progression, progression-free survival, compliance, and safety. An interim analysis was planned to evaluate safety and efficacy.

Results: In this interim analysis conducted on 37 patients (19 in the control group vs. 18 in the experimental group), no difference was observed for the objective response rate (p = 0.25, control 73.7% vs. experimental 55.6%). Concerning clinical benefit, overall survival and time-to-progression, we also failed to show any difference between the two arms. A slight tendency towards longer progression-free survival at 12 months after randomization was observed in the curcumin group (65.5% vs. 41.4%) but this difference did not reach significance (p = 0.14).

Conclusion: In this study, we showed for the first time that adding oral curcumin for advanced and metastatic breast cancer patients treated with first or second-line docetaxel was not efficacious, although safe. Consequently, this study was stopped for reasons of futility. Further studies with a larger number of patients, a different curcumin preparation, a longer treatment period and a pharmacokinetic evaluation of curcumin are needed to explore the real efficacy of this compound.

Keywords: advanced and metastatic breast cancer; chemotherapy; curcumin; docetaxel; phytotherapy.

Figure 1

Study design. At enrollment and after patients' written informed consent pretreatment data were collected, including medical history, previous treatments, physical examination (weight, height, body mass index, and ECOG performance status), breast examination and scans (CT scan and bone scan), and a complete biological exploration. Breast examination, CT scan and bone scan were repeated after cycle 3 and cycle 6. C, chemotherapy cycle; CT scan, computerized tomography.

Figure 2

Participant flowchart. A total of 42 patients were enrolled according to the inclusion criteria. A 1:1 randomization was conducted with stratification on the centre and the number of chemotherapy lines; 22 patients were assigned to arm A (docetaxel alone) and 20 patients to arm B (docetaxel + curcumin). The interim analysis was conducted on the modified ITT population, that is, patients who were given at least one dose of docetaxel + curcumin. Among them, five patients (three in arm A and two in arm B) were excluded from the analysis: one patient was wrongly included and did not meet the inclusion criteria, three other patients withdrew their consent and one patient stopped the study on the investigator's decision. ECOG, Eastern Cooperative Oncology Group; ITT, Intention‐to‐treat.

Figure 3

Objective response rate (ORR) in the mITT population.

Figure 4

Overall survival in the mITT population.

Figure 5

Time‐to‐progression in the mITT population.