BLOGGERS: MARK SCHOLZ, MD & RALPH H. BLUM

The co-authors of Invasion of the Prostate Snatchers, blog alternate posts weekly. We invite you to post your comments.

Tuesday, March 8, 2016

Modern Taxotere Chemotherapy for Prostate Cancer

BY MARK SCHOLZ, MD


In prostate cancer, the word “chemotherapy” is essentially synonymous with Taxotere (docetaxel). Taxotere is by far the most common chemotherapy medicine for prostate cancer. Taxotere is an active agent that is also employed for the treatment of breast cancer and lung cancer.  Jevtana, which has many similarities to Taxotere, more than any differences, is the second most commonly used type of chemotherapy. Taxotere (and Jevtana) are administered intravenously every three weeks in a cyclical fashion.

These agents are typically used to treat advanced metastatic prostate cancer. Men with preexisting bone pain usually notice significant improvement within a week or two of starting therapy.  Another sign that the Taxotere is working is PSA levels decline.  If the PSA does not decline immediately, Taxotere should still be continued for at least two or three cycles before concluding the treatment is not working. An initial increase in PSA for 30-60 days is not an indication to stop Taxotere because on occasion men have a bump upward in the PSA, a “flare” from the dying cancer cells.  However, if the PSA continues to rise after three cycles, it indicates that the Taxotere is not working.

Cancer response rates can be further improved by using Taxotere in combination with Carboplatin.  Carboplatin is also administered intravenously and can be conveniently administered at the same time as the Taxotere. In patients who have normally functioning bone marrow and normal kidney function, a small dose of Carboplatin, say 200 mg, can be safely administered along with full-dose Taxotere.  Carboplatin is well-tolerated though occasional side effects include low-grade nausea, numbness in the hands or feet and tiredness.

Taxotere administered in combination is with Avastin and Revlimid is another very active combination that will induce a cancer response in most men. Avastin, which is FDA-approved for colon cancer but not prostate cancer, is an angiogenesis inhibitor given intravenously every two weeks.  It is generally well-tolerated but requires concomitant blood thinners due to a higher risk of blood clots.  Avastin can also cause slow wound healing and can't be used before or after surgery. Revlimid oral agent that is FDA-approved for a type of bone cancer called myeloma.  Like Avastin, it also functions by blocking new blood vessel growth. When using Revlimid in combination with Taxotere and Avastin we typically limit the Revlimid dosage to 5 mg daily.  Side effects at this dose range are rare though occasionally platelet counts can be suppressed.

A study using these three agents in combination that showed very high response rates was published by Dr. Figg from the National Cancer Institute.  This same study also reported a high frequency of fairly notable side effects including numbness of the hands and feet as well occasional cases of jaw damage, a condition called osteonecrosis.  Despite these significant problem, Dr. Figg reported that the vast majority of the men achieved significant remissions and that the remissions tended to be quite long lasting.  

Aggressive combination protocols like these require various supportive measures to be successful.  Defending against low white blood cell counts with an immune stimulator such as Neulasta should be considered routine. Neulasta is a powerful medicine that stimulates the bone marrow to manufacture white blood cells more quickly and in greater numbers. Side effects are rare but occasionally, serious but transient episodes of lower back pain can occur.

Another bone marrow stimulator, Aranesp, can defend against the development of progressive anemia. Anemia is a common in men with prostate cancer and can be due to hormone therapy, chemotherapy, or even from the prostate cancer invading the bone marrow. Symptoms of anemia are shortness of breath and fatigue. Timely and appropriate use of Aranesp helps to maintain normal red blood cell counts and can reduce the need for blood transfusions.

Taxotere usage has been greatly postponed in men with metastatic prostate cancer ever since the FDA approval of Xtandi and Zytiga. These agents induce meaningful remissions with far fewer side effect than Taxotere.  However, patient tend to have a rapid and virulent progression of the cancer after Zytiga and Xtandi stop working.  Taxotere, possibly in combination with Carboplatin should probably be implemented quickly in most cases. 

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