#castrate-resistant

There has been historical evidence showing that in men with metastatic castration-resistant prostate cancer (mCRPC) when Taxane based chemotherapy like docetaxel or cabazitaxel is given along with a platinum chemotherapy drug, there is increased positive activity. This activity has not been evaluated in any randomized trial. 

A study, reported in the Lancet, evaluated whether adding Carboplatin (a platinum drug) to cabazitaxel would improve outcomes.

The study involved a phase 1–2, open-label, randomized study in men with progressing metastatic castration-resistant prostate cancer. 

In the phase 1 part of the study, the subject men were given intravenous cabazitaxel and intravenous Carboplatin. All of the participating men received growth factor support and oral prednisone 10 mg daily. The primary endpoints of this phase 1 study were to determine the maximum tolerated dose of the combination. The phase 2 involved evaluating investigator-assessed progression-free survival. This trial is registered at ClinicalTrials.gov, number NCT01505868.

The study period ran between Aug 17, 2012, and May 11, 2015. In the phase 1 study, nine men completed as planned. In the phase 2 trial, one hundred and sixty (160) men were randomly assigned to receive either cabazitaxel (n=79) or cabazitaxel plus Carboplatin (n=81). 

During phase I, grade 3 adverse events were anemia (n=2), fatigue (n=1), thrombocytopenia (n=1), hypomagnesaemia (n=1), diarrhea (n=1), hypokalemia (n=1), anorexia (n=1), and dehydration (n=1), and no grade 4 adverse events occurred. 

No dose-limiting toxicities were observed.  

In the phase 2 study, the most common grade 3–5 adverse events were fatigue (7 [9%] of 79 in the cabazitaxel group vs 16 [20%] of 81 in the combination group), anemia (3 [4%] vs 19 [23%]), neutropenia (3 [4%] vs 13 [16%]), and thrombocytopenia (1 [1%] vs 11 [14%]). There were no treatment-related deaths.

A maximum tolerated dose of cabazitaxel of 25 mg/m 2 and Carboplatin of AUC 4 mg/mL per min was selected for phase 2. At a median follow-up of 31 months, the combination improved the median progression-free survival (PFS) from 4.5 months to 7.3 months. 

The study concluded that adding Carboplatin to cabazitaxel showed improved clinical efficacy compared with cabazitaxel alone for men with metastatic castration-resistant prostate cancer. Although adverse events were more common with the combination, the treatment was safe and generally well-tolerated.