Glossary
Chemotherapy
Taxotere is the mainstay of chemotherapy treatment for prostate cancer. However, since its FDA approval, improved response rates have been achieved by combining it with additional agents such as Carboplatin, Xeloda, Revlimid, Thalidomide, and Avastin. Other forms of chemotherapy that can be effective if Taxotere in combination stops working are Jevtana, Mitoxantrone, Adriamycin, Ixempra, Alimpta and Emcyt in combination with either Velban or Taxol.
Taxotere
Taxotere is presently the most active chemotherapeutic agent in prostate cancer. Two large randomized studies showed longer survival with Taxotere compared to mitoxantrone, another FDA approved medicine. Taxotere has two basic roles to play in men with prostate cancer. The first is treating men with advanced metastatic disease. In this role Taxotere can be used as a single agent or combined with other medications such as Carboplatin, Avastin, Xeloda and Revlimid to further enhance the anti-cancer effect. Taxotere's other use is as a preventative agent for early stage prostate cancer - where the cancer profile suggests a high risk of relapse or a high risk for the early development of hormone resistance.
Taxotere is administered intravenously. There are two popular administration schedules, a larger dose administered every three weeks and a lower dosage administered weekly. In more advanced cases, studies seem to indicate that the every three week protocol is more effective. However, the larger doses cause a higher incidence of low white blood cell counts and a greater degree of fatigue. Low white counts can be counteracted with other medications such as Neulasta or Leukine. Also for some individuals, weekly infusions may be considered less convenient as they require a greater number of doctor visits. So there are advantages and disadvantages to the two different schedules. Typically younger men are started on the every three week protocol. If tiredness is excessive the program can be changed to weekly administrations. Men who are weaker or more elderly are often given weekly treatment at the outset.
Side-effects of Taxotere vary between the two treatment schedules. Reversible hair loss tends to be more severe using the three week schedule. Nausea is not very common with either schedule because anti-nausea medicines are quite effective. Taxotere can affect the taste buds making food taste funny. "Icing the tongue" by keeping ice chips in the mouth during the infusion is advisable during treatment and continuing afterward for an additional hour.
Weakening of fingernails is much more commonly associated with once-a-week Taxotere. For this reason the finger tips should be "iced" during and immediately after the infusion for the men who are on weekly therapy. Irritation of the tear ducts is another side-effect that occurs more commonly with weekly Taxotere. This effect is usually noticed when men have increased tear formation because the ducts are not draining properly. We recommend the use of artificial tears during and after each treatment to flush the Taxotere from the surface of the eye to prevent this problem. However, if improper draining persists it may be necessary to place a temporary spacer in the tear ducts to avoid long-term scarring.
Another side effect that can develop over time is a condition called neuropathy. Neuropathy is numbness in the fingers and toes. Generally these symptoms are mild and slowly reverse over time after the Taxotere is stopped. High doses of Glutamine, an amino acid, can minimize the severity of the neuropathy. Other rare side-effects that can occur with either protocol include: rash, liver inflammation or diarrhea. These problems are reversible with treatment adjustments.
Overall Taxotere is well-tolerated. We published a pilot trial in 2001 evaluating the tolerability of Taxotere in elderly men. The average age of the group was 78. The oldest man was 87. Using the weekly protocol we found that Taxotere could be tolerated by almost anyone. In that study 17 out of 20 men completed a full course of therapy. The three men who decided to stop the treatment before finishing the full course did so because they felt excessively tired. A copy of this published report is posted on this web site.
So in summary, Taxotere has proven to prolong survival in men with prostate cancer. Questions still exist about its exact role for the early-stage, high-risk, prostate cancer patient. Until more information becomes available the optimal way to use Taxotere can only be decided through a partnership between an informed patient and a doctor who is an expert in the treatment of prostate cancer.
Taxotere Combinations
Taxotere benefits about two-thirds of men with prostate cancer. Higher response rates are achievable by combining Taxotere with other active agents. Carboplatin is an injectable agent that can be conveniently administered at the same time as the Taxotere. Dose is dependent on kidney function. Typically we administer 100-200 mg weekly and follow the platelet count closely. If the platelet count falls below 100 we temporarily hold the Carboplatin until they recover above a 100 after which therapy can be resumed. Carboplatin in these doses is well-tolerated though occasional side effects include low-grade nausea, numbness in the hands or feet and tiredness.
Another very active Taxotere combination is Avastin and Revlimid. Avastin is an angiogenesis inhibitor given intravenously every two weeks that is FDA approved for colon cancer. It is well-tolerated but requires blood thinners to avert blood clots. Avastin can also cause slow wound healing and can't be used before or after surgery. Revlimid is an oral agent related to Thalidomide that also inhibits angiogenesis. When using Revlimid in combination with Taxotere and Avastin we typically use a small dose of only 5 mg daily. Side effects at this dose are rare though occasionally the platelet count can be suppressed.
Another medication that can increase the effectiveness of Taxotere is Xeloda. Xeloda is an oral medication that is FDA approved for breast cancer and colon cancer. We have seen good responses in men resistant to Taxotere when treating them with the combination of Taxotere and Xeloda. Possible dose-related side effects of Xeloda are pain in the hands and feet and diarrhea.
Jevtana & Other Chemotherapy
Jevtana was FDA approved for the treatment of Taxotere resistant prostate cancer in 2010. Its chemical structure is similar to Taxotere except that it has been slightly modified to enhance its anticancer efficacy. We have witnessed some dramatic clinical improvement in men with Taxotere resistant disease confined to wheelchairs who have become ambulatory when treated with Jevtana. The side effects of Jevtana are similar to Taxotere though there is a slightly higher incidence of diarrhea. The treatment protocol consists of intravenous injection every three weeks.
We have also had good results treating Taxotere resistant patients with Taxol, another drug that is chemically related to Taxotere, in combination with an oral medication called Emcyt. Emcyt is a combination of two medicines mixed in one pill, estrogen and an old chemotherapeutic agent called Mustergen derived from of all things, World War I era mustard gas. Emcyt was originally used as a single agent to treat prostate cancer in the 1970s and 80s. Side effects from the estrogen portion of the pill are blood clots, nausea and breast enlargement. The Mustergen portion of the pill can cause low blood counts though these effects are usually mild.
Other agents to consider are mitoxantrone, a very mild type of chemo that is well-tolerate and can help ameliorate bone pain, adriamycin, which is a somewhat stronger version of mitoxantrone and Ixempra or Alimpta, two medications that are FDA approved to treat lung cancer but have also shown benefit in men with prostate cancer.
