577 Background: Docetaxel formulated inpolysorbate 80 and ethanol (Docetaxel) is among the most active agents in the treatment of breast cancer. The primary rationale for developing nanosomal docetaxel lipid suspension (NDLS) is to improve the drug’s safety profile by eliminating polysorbate 80 and ethanol from docetaxel formulation. Previously, we conducted a clinical study comparing pharmacokinetic parameters of NDLS and docetaxel at 75 mg/m2. The log transformed NDLS/docetaxel ratio for Cmax and AUC0-t was 149.3% and 119.3% respectively. The higher systemic availability of NDLS prompted us to conduct current efficacy study. Methods: 72 locally advanced or metastatic breast cancer patients were enrolled into the study after failure of prior chemotherapy. The mean age for the enrolled patients was 47 years and the racial make-up of the study was 100% Asian. Patients were administered NDLS or docetaxel at 75 mg/m2 as per randomization schedule, by IV infusion for one hour in each cycle of 21 days. Each patient received maximum of 6 cycles of NDLS or docetaxel. No premedication was given to the patients in NDLS treatment group. Results: Safety - The total number of post-dose AEs observed in the study was 510. The breakdown by treatment groups is as follows: AEs were reported in 91.30% and 93.88% patients who received the docetaxel and NDLS respectively. There were 34 SAEs in the study, out of which 04 SAEs resulted in death of the patients (3 in docetaxel and 1 in NDLS). Efficacy - The results showed that 4.2% patients had complete response (CR) in NDLS treatment group while there was no CR in docetaxel treatment group. Further, 31.3% partial response rate (PR) was observed in NDLS treatment group and 26.3% in docetaxel treatment group. Overall response (CR+PR) rate was 35.4% in NDLS treatment group and 26.3% in docetaxel treatment group. Stable disease (SD) was observed in 45.8% patients in NDLS group and 63.2% patients in docetaxel group. Conclusions: Overall, the NDLS was well tolerated in the multiple doses of 75 mg/m2 and found to increase response rate compared to docetaxel in breast cancer patients. Clinical trial information: CTRI/2010/091/000610.
Role of Curcumin in reducing toxicity and adverse effects in locally advanced and metastatic breast cancer patients
