Life Extension is a global authority on health, wellness and nutrition

Many studies that evaluated the efficacy of various secondary treatments predated the days of PSA testing. In these studies, responses were evaluated by improvement in symptoms such as bone pain, or by reduction in tumor size on bone scans or CT scans. Based upon the limited sensitivity of scans to assess tumor response, older studies may have missed patient responses that might have been noted if PSA testing were available.

Past studies may have also underestimated the importance of drug absorption, proper drug dosing based on elimination half-life, dose intensity, and altered drug metabolism. Treatments that were labeled as ineffective in the past may conceivably turn out to be more effective when given to patients with less tumor volume and under better pharmacological conditions. In a thorough review of the literature, long-lasting responses to secondary therapies have been documented. What patient or treatment-related variables were present in such responding patients?

Dose Intensity

Dose intensity is a term used to compare relative amounts of a drug administered in a given unit of time. For example, compare the relative dose intensities of Regimens A and B. Regimen A delivers a dose intensity that averages 2000 mg a month. Regimen B delivers a dose intensity that averages 4000 mg a month.

Regimen A, with its lower, more frequently administered dose, may have less toxicity due to lower peak blood levels than Regimen B, with its higher but less frequently administered dosing. For example, Taxotere administered every 3 weeks at 70 mg/m2 has a dose intensity of approximately 93 mg/ m2 a month. Taxotere administered weekly at 25 mg/m2 has a dose intensity of 100 mg/m2 a month. The latter regimen is associated with far less toxicity due to the lower but more frequent drug doses. The efficacies of these regimens have not been reported in a randomized trial. Low weekly doses of Taxotere are, in our experience, without question a more patient and friendly regimen compared to the standard, higher dose Taxotere protocol.

Exposure Time

Most chemotherapy agents kill cancer cells that are actively multiplying. PC cells generally grow slowly, which mandates that they receive a longer exposure time to the chemotherapy or other anticancer agent. Examples of ways to increase exposure time include daily oral therapy; a more frequent schedule of intravenous administration; or use of low-dose, continuous intravenous infusions administered by means of a computerized pump through a venous access device, such as a Port-a-Cath. Such protracted infusion delivery increases exposure time while decreasing the toxicity of chemotherapy. Drugs such as Cytoxan and Adriamycin have a much lower toxicity profile and a higher therapeutic index when given in this manner. We currently have a protocol in progress that employs Cytoxan, an active agent in PC, given as a continuous infusion over 120 hours. This is given in conjunction with another agent, 5-Fluorouracil, during the same period of time. This combination has shown high activity in advanced refractory breast cancer in a pilot trial. Since prostate and breast cancer are strikingly similar in so many ways, we have begun this program in advanced PC to utilize a long exposure time of drugs that are known to be active in PC. Moreover, the use of low-dose continuous chemotherapy has another advantage in lowering the toxicity of the drugs. Therefore, the therapeutic index, a measurement of efficacy and side effects, is greatly enhanced with protracted chemotherapy administration. Unfortunately, many oncologists are not familiar with the use of ambulatory infusion pumps or venous access devices such as the Port-A-Cath.

Bone Marrow Support

One of the essential factors in the successful management of the cancer patient is adequate supportive care. This involves multiple factors in the medical and surgical management of the patient, and includes psychological support as well. With the advent of agents that can stimulate the bone marrow, we now are able to give chemotherapy at higher doses by supporting and/or preventing toxicity such as low white blood cell counts, anemia, and low platelet counts.

A low white blood cell count (also called granulocytopenia or neutropenia) is a major dose-limiting factor with chemotherapy and is the cause for the most serious side effect of chemotherapy- infection. AIPC patients who receive agents that stimulate the bone marrow to produce white blood cells tolerate this chemotherapy side effect remarkably better. Neupogen or Leukine support reduces or eliminates the number of hospitalizations for infection associated with chemotherapy, and it reduces other problems such as mouth and throat sores.

A low red blood cell count, or anemia, can also be a significant source of concern for AIPC patients receiving chemotherapy. Anemia is usually already present to some degree in AIPC patients due to their ADT. Anemia, left untreated, can cause severe weakness, shortness of breath, dizziness, mental status changes, and chest pain. The availability of Procrit to stimulate bone marrow red blood cell production can help minimize the adverse effect severe anemia can have upon the AIPC patient. The use of Procrit has largely replaced the need for blood transfusions.

A low platelet count, also called thrombocytopenia, is another dose-limiting factor with chemotherapy and is the cause for a serious side effect of chemotherapy-bleeding. Until recently, thrombocytopenia could delay chemotherapy, cause dosage reductions, or even cause changes in drug therapy. Neumega has recently become available as a marrow stimulant specific for platelet production, and its use may treat patients for low platelet counts.

Other Supportive Care

A medical oncologist should offer the most effective medications or other approaches to maximize the level of supportive care for the AIPC patient receiving chemotherapy. Other chemotherapy side effects include the following

Unfortunately, there are no medications or approaches available that will prevent loss of hair from chemotherapy. However, hair will grow back in the weeks after therapy is stopped, and may actually begin to grow back during continued chemotherapy treatments.

Certain intravenous chemotherapy drugs, if they accidentally leak out of the vein and into surrounding tissues, can cause a significantly damaging extravasation injury. Drugs that can cause extravasation injuries are known as vesicant chemotherapy agents. To prevent potential extravasation injuries, vesicant chemotherapy should be given with caution to patients with poor-quality veins, or patients who are to receive drugs as a protracted infusion over several days. In most cases, it may be preferable in such patients for them to have a central venous catheter or access device, e.g., Port-A-Cath, placed before therapy is started. This not only avoids a potential extravasation injury, but also preserves access to a patient's veins to draw blood. If chemotherapy extravasation does occur, 70% DMSO applied topically prevents tissue injury and should be administered as soon as possible, and at least 4 to 6 times a day until the site of extravasation is fully healed. If stinging occurs with DMSO application, the patient should wipe off the remaining DMSO and apply aloe vera gel to the skin.

It is very important that a patient promptly report any unusual symptoms or side effects during chemotherapy treatment to his physician to be sure that it is not, or does not become, a major problem. Patients receiving vesicant chemotherapy through a peripheral (hand, arm, or leg) vein should inspect the chemotherapy injection site for several days after each treatment.

Concepts in AIPC Management

Due to our concern for the emergence of androgen independence in PC, the following principles are relevant until we have a better understanding of hormone sensitivity and independence.

Continuation of PROSTATE CANCER: CHEMOTHERAPY