Docetaxel Chemotherapy for Prostate Cancer: How Does it Work?

Docetaxel is a chemotherapy drug typically given intravenously (IV), and usually combined with prednisone, an anti-inflammatory steroid medication, to treat castration resistant metastatic prostate cancer. It may also be used in combination with hormone therapy as initial therapy for castration sensitive metastatic prostate cancer. Its origins lie in the rare yew tree, Taxus baccata, from which it is extracted and chemically modified.

The main way that docetaxel works is by inhibiting cancer cell growth. It achieves this by interrupting microtubule development, an essential structural component of cells – thus stopping the cancer in its tracks.

Microtubules generally help to determine cell shape, movement and division, which are critical to helping cancer cells navigate and spread through the body’s tissues. In order to do this, microtubules go through continuous cycles of breakdown and renewal to direct the cells where they need to go.

This process is facilitated by rearranging smaller building blocks, tubulin, over and over again to build up the microtubules, and then disassembling them. Once a microtubule has been built, docetaxel interferes by binding to these smaller building blocks, preventing further disassembly. With no more free building blocks, new microtubules can no longer form and cell division is halted, achieving docetaxel’s goal of inhibiting cancer cell growth.

Under laboratory testing, docetaxel was found to have double the affinity of paclitaxel (a chemotherapeutic drug from the same taxane family), to bind to tubulin and block cell division. However, this has yet to be compared in prostate cancer specifically.

Interestingly, docetaxel has also managed to target prostate cancer cells through another method: inhibiting the anti-apoptotic protein Bcl-2. This then triggers programmed cell death, sending a cascade of signals to direct the cell to break down other parts of the cell structure as well.

Why is IV delivery preferred for docetaxel?

Delivering docetaxel by IV drip is preferred as it ensures higher bioavailability, which increases the chances of it reaching and acting on your tumor cells.

This direct entry into your bloodstream allows the drug to avoid going through the oral route by the digestive tract. Your digestive tract works hard to eliminate toxic materials from your body through the liver and kidneys, and this includes drugs as well. While this usually works in your favor, when it comes to your treatment, this works against you, increasing the risk of the drug being eliminated from your body before it even reaches the tumor cells. By bypassing the digestive tract, a higher concentration of your drug will be guaranteed to reach your cancer cells as soon as possible.

However, this also comes with additional caveats — while much better at reaching tumor cells, the IV route means that high amounts of the drug will run through your bloodstream, exposing your organs to a high concentration of the cell-killing drug.

Why is docetaxel combined with prednisone?

Docetaxel is often combined with prednisone for treating castration resistant metastatic prostate cancer. The rationale for this combination is to mitigate treatment side effects, rather than to improve treatment responses. For example, as a corticosteroid, prednisone has anti-inflammatory properties that help to relieve the pain and swelling that comes with metastases (e.g. bone pain).

Furthermore, during the original clinical trials of docetaxel for prostate cancer, the drug was not tested by itself, and so its utility has never been truly demonstrated alone.

How long is docetaxel treatment?

The recommended treatment schedule is an hour-long IV drip every three weeks, known as one cycle of treatment. Research suggests that eight docetaxel cycles may be optimal, assuming that it continues to work effectively against your cancer. However, this may vary based on your body’s tolerance to the side-effects of the drug.

All patients’ bodies are different, and you may face only a few, or more of side effects like those listed here. If your reaction is too severe, your doctor may consider reducing your dose in order to mitigate some of these effects. Some commonly reported side effects include:

Based on the known side effects of docetaxel, the following symptoms may indicate a more serious reaction, and should be immediately reported to your doctor for further review:

• Vision changes
• Neurologic reactions (e.g. tingling, numbness, burning in hands or feet, or weakness in your limbs)
• Irregular and/or rapid heartbeat, severe shortness of breath or fainting
• Fluid retention or swelling

Some key features you should know about docetaxel treatment:

• A recurring check of your blood count will likely be recommended to watch for any issues with blood cell production and resultant low blood counts, a common side effect.
• Due to the risk of fetal toxicity, if your partner is of reproductive potential, effective contraception (e.g. condoms or female birth control pills) should be used when needed, up to three months after the final injection.
• If you intend to conceive after, you should note that there is a risk of infertility for you. Unfortunately, this risk is commonly associated with prostate cancer treatments, as most target the reduction of the sex hormones or the removal of the prostate in order to limit cancer spread.

Ultimately, docetaxel currently provides a second chance to prolong survival for advanced prostate cancer patients who have already developed resistance to hormone therapies. Unfortunately, resistance against docetaxel tends to arise eventually. Researchers are working to address this weakness, and combination therapies may finally provide an answer in the future. Furthermore, advances in nanoparticle delivery may eventually discover a more efficient and safe delivery of this chemotherapeutic drug, and succeed in minimizing its associated side effects.