Zytiga
Abiraterone Acetate
FDA approved oral medication for metastatic high-risk castration-sensitive prostate cancer and metastatic, castration resistant prostate cancer
Manufactured by Johnson and Johnson
Zytiga is FDA approved to treat men with both metastatic high-risk castration-sensitive prostate cancer and metastatic, castration resistant prostate cancer.
Initially approved in April of 2011 in the post chemotherapy (Docetaxel) setting for men with metastatic CRPC. Abiraterone and prednisone were compared to placebo and standard therapy.
- Improved survival 15.8 months versus 11.2 months
- Improved time to radiographic progression benefit
- Improved PSA decline
- Improved pain
- Trial stopped early as benefit of Abiraterone significant enough to allow access to drug to all
The FDA expanded the use of Zytiga in 2012 in the pre-docetaxel setting based on the randomized phase 3 trial of abiraterone and prednisone versus prednisone alone in men with asymptomatic or minimally symptomatic, metastatic CRPC.
- Improved radiographic progression-free survival 16.5 months versus 8.3 months
- Improved overall survival 34.7 months versus 30.3 months
- Improvement in time to symptomatic deterioration
- Improvement in time to chemotherapy initiation
- Improvement in time to pain progression
- PSA progression-free survival improved significantly with abiraterone treatment
- PSA declines (62% vs. 24% with >50% decline)
- Radiographic responses (36% vs. 16% RECIST responses) were more common.
Recently(2018) Zytiga received a new indication for the treatment of metastatic, hormone-sensitive prostate cancer. This was based on the LATTITUDE trial. The trial was Abiraterone plus prednisone and ADT versus ADT alone.
- Improved overall survival
- Improved radiographic progression free survival 33.0 months versus 14.8 months
- Improved time until pain progression
- Improved time to subsequent therapy
- Improved time to chemotherapy
- Improved PSA progression
- Improved time to next symptomatic skeletal event
How does Zytiga work?
Zytiga is an androgen synthesis inhibitor which reduces androgen levels to very low levels (undetectable) by blocking an enzyme which is necessary for the production of testosterone. It is believed that the blockade occurs for both testicular and adrenal androgens along with blocking production of testosterone made by the tumor cells themselves (autocrine).
In doing so the irreversible blockade of the enzyme system in controlling androgen production from cholesterol can reduce testosterone of all sources to undetectable levels. Testicular androgens, adrenal androgens and tumor produced androgens are all blocked with the use of Zytiga.
Significant findings included:
Primary endpoints
- Radiographic progression-free survival was improved by treatment from 8.3 to 16.5 months
- Overall survival was improved 34.7 months vs. 30.3 months with median follow up 49.2mo
Secondary endpoints
- Improvement in time to symptomatic deterioration
- Improvement in time to chemotherapy initiation
- Improvement in time to pain progression
- PSA progression-free survival improved significantly with abiraterone treatment
- PSA declines (62% vs. 24% with >50% decline)
- Radiographic responses (36% vs. 16% RECIST responses) were more common.
It is believed that Zytiga also works work by not allowing the tumor itself to make androgens (fuel) that can be used in an autocrine fashion. In doing so the irreversible blockade of the enzyme system in controlling androgen production from cholesterol can reduce testosterone of all sources to undetectable levels. Testicular androgens, adrenal androgens and tumor produced androgens are all blocked with the use of Zytiga.
Dosage
1000 mg (4 250 mg tabs) once daily. No food should be consumed at least 2 hours before or at least 1 hour after. Tablets should be swallowed whole with water. Additionally Prednisone 5 mg is taken twice daily with food.
Advantages
This drug can be used before or after chemotherapy in men with metastatic, CRPC which allows patients to treat their cancer earlier.
Adverse effects
There is an increase in the mineralocorticoid deoxycorticosterone which can lead to the common side effects associated with mineralocorticoid excess.
The most common significant adverse effects are as follows:
- high blood pressure 22% (4% severe)
- low serum potassium levels 17%
- peripheral edema or fluid retention 28%
Other adverse effects with abiraterone/prednisone (>5%) were fatigue, joint pain, nausea, hot flushes, diarrhea, vomiting, upper respiratory infections, cough, headache, changes in lipids, changes in blood sugars.
Adrenal problems may occur if you stop taking Prednisone.
Liver function tests need to be monitored as there may be an increase resulting in drug discontinuation or dose modification.
Zytiga should never be taken with food as it can change absorption significantly and alter efficacy and adverse effects. (www.zytiga.com).
Zytiga should never be taken with food as it can change absorption significantly and alter efficacy and adverse effects.
The most common adverse drug reactions that resulted in drug discontinuation were increased aspartate aminotransferase and/or alanine aminotransferase (11%–12%), or cardiac disorders (19%, serious in 6%). Thus, monitoring of liver function, potassium and Phosphate levels, and blood pressure readings on a monthly basis, at least initially is warranted during abiraterone/prednisone therapy. Symptom-directed assessment for cardiac disease also is warranted, particularly in patients with pre-existing cardiovascular disease.