Phase I dose escalation trial of docetaxel plus Curcumin in patients with advanced and metastatic breast cancer

 

Cancer Biol Ther. 2010; 9(1):8-14.

 

Breast cancer is one of the most common types of cancer in women across any race or ethnicity and is one of the leading causes of death from cancer in women. In the US 220,097 women were diagnosed with breast cancer in 2011, the death alone with this cancer numbered more than 40,000 as per the data from Center for Disease Control (CDC). Depending on the kind of breast cancer and how far it is spread, different treatments are recommended including hormonal therapy, chemotherapy, surgery or radiation therapy.

One of the current drugs used in the treatment regimen is Docetaxel, which is a mitotic inhibitor promoting microtubule assembly, prevents depolymerization and results in failed cell division and cytotoxicity due to arresting cells at G2/M transition.

The anticancer benefits of Curcumin arise from its anti-inflammatory, antiproliferative and apoptotic effects. In previous studies on various cancers, Curcuminoids have shown to increase the sensitivity of cancer cells towards the existing drug therapies such as Doxorubicin, Tamoxifen, Cisplatin etc.

 

Objective:

To evaluate the role of Curcumin supplementation on breast cancer patients, who were on Docetaxel (100 mg/m2) regimen.

 

Study Design:

In this open-label, Phase I trial, 14 eligible subjects were enrolled who had metastatic or advanced breast cancer and were administered Docetaxel at a dose of  100 mg/m2 1 h perfusion, every 3 weeks for 6 cycles with total 63 cycles. These patients received Curcumin 500 mg/day for seven consecutive days at each cycle from day -4 to day +2 days of therapy.

As a primary end-point, maximum tolerable dosage of Curcumin was determined. In the Phase I trial, 6 dose levels of Curcumin were evaluated (500 mg, 1000 mg, 2000 mg, 4000 mg, 6000 mg and 8000 mg) for dose-related toxicities. The Maximum tolerable dose was found to be 8000 mg/day in patients suffering from breast cancer.

The parameters evaluated during the trial (i.e. at baseline and at the end of the study) included fasting glucose level and lipid profile (total cholesterol, LDL-C, HDL-C and Triglycerides) along with liver and kidney function tests.

 

Results:

  • No incidence of toxicity was observed on this tested combination, which included monotherapy of Docetaxel. 
  • The antiangiogenic activity of the combination was evaluated with the vascular endothelial growth factor (VEGF) expression and it was found that Curcumin/Docetaxel combination reduced the expression of VEGF after three cycles of treatment.
  • Curcumin potentially reduced the tumor cell resistance towards Docetaxel which might be by improving systemic bioavailability of the drug due to its effect on P-glycoprotein in the gut lining

 

Conclusion:

The study concluded with positive results on the safety and efficacy of Curcumin C3 Complex® combination with Docetaxel drug therapy regimen in advanced and metastatic breast cancer patients.

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