xtandi in advanced prostate cancer: A promising drug for chemorefractory disease

We had one patient -50 year old gentleman diagnosed with hormone refractory prostate cancer. His PSA was 100 ng/ml with multiple bony metastases and iliac and paracaval lymphadenopathy with left ureteric obstruction.

He had locally advanced prostate disease with hematuria.We treated with High Intensity Focussed Ultrasound(HIFU) to control the local disease and left ureteric stenting.We also started him on   docetaxel chemotherapy with prednisolone support.He did not show good response ; his PSA came down only to 90 ng/ml. We started him on Xtandi and were planning for samarium radio-isotope therapy for bony pains but he did show remarkable symptomatic as well as PSA improvement with Xtandi( after 1 1/2 months the PSA was 75 ng/ml).For now we have dropped our plans for samarium therapy.

 Enzalutamide is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. Enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors and inhibit androgen receptor nuclear translocation and interaction with DNA. A major metabolite, N-desmethyl enzalutamide, exhibited similar in vitro activity to enzalutamide. Enzalutamide decreased proliferation and induced cell death of prostate cancer cells in vitro, and decreased tumor volume in a mouse prostate cancer xenograft model.

XTANDI is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel. U.S. FDA Approves XTANDI(R) (enzalutamide) After Priority Review for Patients With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Docetaxel.

 XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. The recommended dose of XTANDI is 160 mg (four 40 mg capsules) administered orally once daily. XTANDI can be taken with or without food.

The most common adverse drug reactions (≥ 5%) reported in patients receiving XTANDI in the randomized clinical trial were asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension.Xtandi is specially contraindicated in epileptogenic patients.

The efficacy and safety of XTANDI in patients with metastatic castration-resistant prostate cancer who had received prior docetaxel-based therapy were assessed in a randomized, placebo-controlled, multicenter phase 3 clinical trial. The primary endpoint was overall survival. A total of 1199 patients were randomized 2:1 to receive either XTANDI orally at a dose of 160 mg once daily (N = 800) or placebo orally once daily (N = 399). All patients continued androgen deprivation therapy. Patients were allowed, but not required to continue or initiate glucocorticoids. The pre-specified interim analysis at the time of 520 events showed a statistically significant improvement in overall survival in patients on the XTANDI arm compared to patients on the placebo arm