Can You Take Zytiga after Provenge?

Can you take Zytiga after Provenge? This question is important for patients with castration-resistant prostate cancer. Combining or sequencing treatments is becoming much more standard in oncology, but we often do not have a lot of data to know what is a best practice.

While great strides have been made in the treatment of prostate cancer, significant challenges remain in the treatment of castration-resistant prostate cancer. In oncology, physicians often combine multiple therapies with a different mechanism of action in order to more effectively treat cancer. The hope is that improved survival may be possible when cancer is attacked from more than one avenue.

Because Provenge and Zytiga each have a different mechanism of action, there is interest in combining the two agents. However, key questions remain. What is the best sequence of these drugs? How can these different drugs be optimally combined to minimize toxicity and maximize survival?

What is Zytiga?

Zytiga (abiraterone) is an oral pill that decreases levels of testosterone, the hormone that stimulates the growth and spread of prostate cancer. In 2012 the FDA expanded the use of Zytiga for the treatment of castration-resistant prostate cancer in men prior to receiving chemotherapy.

What is Provenge?

Provenge (sipuleucel-T) is an immunotherapy that helps your body attack prostate cancer by stimulating your own immune cells. It is normally used in men who have not responded to hormone treatment, but it can be used before chemotherapy.

Zytiga side effects

Common side effects reported in patients receiving Zytiga include:

  • fatigue
  • joint swelling
  • joint pain
  • swelling and fluid retention
  • hot flush
  • diarrhea
  • vomiting
  • cough
  • high blood pressure
  • shortness of breath
  • urinary tract infection
  • bruising

Additionally, Zytiga is associated with some lab abnormalities including:

  • low blood counts
  • abnormal liver function tests
  • abnormal electrolytes like potassium or phosphorus

Provenge side effects

The Provenge treatment is well tolerated by most patients. Common side effects include:

  • chills
  • fatigue
  • fever
  • joint pain
  • headache
  • muscle aches
  • nausea

How should Provenge and Zytiga be combined?

Provenge is an FDA-approved treatment for castration-resistant prostate cancer with a demonstrated survival benefit that can be given before chemotherapy. Many physicians feel that because immunotherapy takes more time to demonstrate a therapeutic effect, it is the initial choice when a man develops castration-resistant prostate cancer. Additionally, it may make more sense to take Zytiga after Provenge because Provenge is indicated for men who are relatively asymptomatic. Further, because Zytiga is given in an oral form and has minimal side effects, it may be better tolerated by men who are sicker.

There is some data that suggest that men treated with Provenge before receiving chemotherapy had a longer survival. This would indicate that immunotherapy before chemotherapy is the most appropriate sequence of therapies. Also, it is not known how long a patient should wait before receiving Zytiga after Provenge treatment. A 2011 Journal of Clinical Oncology article stated:

“The practical dilemma of the appropriate sequence of use of the two new noncytotoxic agents (sipuleucel-T and abiraterone) is being addressed by trials that are under development. For now, given the broader window of applicability of abiraterone and the longer time required to develop an immune response with sipuleucel-T, if both agents are to be used, it seems reasonable to administer sipuleucel-T first with Abiraterone after additional disease progression.”

However, in 2012 an Independent Data Monitoring Committee stopped a Phase 3 study of Zytiga plus prednisone for the treatment of asymptomatic castration-resistant prostate cancer in patients who had not received chemotherapy when there appeared to be a clear treatment benefit. This led to FDA approval for the use of Zytiga in men before chemotherapy.

Given the current evidence, it seems the answer to our initial question is that it depends. It may be preferred that you take Zytiga after Provenge for some of the previously stated reasons, however, this is by no means a definitive recommendation. Current clinical trials are examining this hypothesis and will have preliminary results soon.

Read more in our Prostate Cancer Health Center.

References

Liu JJ, Zhang J. Sequencing systemic therapies in metastatic castration-resistant prostate cancer. Cancer Control 2013 Jul; 20(3)

Small EJ, de Bono JS. Prostate cancer: Evolution or revolution? The Journal of Clinical Oncology 2011 Sep; 29(27): 3595-98


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