Approximately 50 percent of all men diagnosed with prostate cancer will someday have metastatic disease. When metastatic prostate cancer progresses after initial hormonal therapy, it is referred to as hormone-refractory. Hormone refractory metastatic prostate cancer is at the present time not curable, and all attempts at therapeutic intervention have been based on palliating the disease and reducing bone pain. Because there is no standard treatment for hormonerefractory disease, new therapeutic strategies are definitely needed. A recent strategy that seems to hold some promise, which is in a phase III clinical trial at the Oregon Health and Science University Cancer Institute in Portland, Oregon, under the leadership of oncologist Tomasz Beer, M.D., is the use of a blend or combination of vitamin D and a chemotherapy drug known as Taxotere (docetaxel).
“It’s becoming increasingly clear that vitamin D has a host of effects in the body, especially on the growth of tumor cells,” said David Feldman, M.D., of Stanford University at a seminar sponsored by the American Institute for Cancer Research in Washington, D.C., in 2002. Dr. Feldman and colleagues concluded that “Vitamin D is anti-proliferative and promotes cellular maturation.” It seems clear, they add, “that vitamin D must be viewed as an important cellular modulator of growth and differentiation. Vitamin D has the potential to have beneficial actions on various malignancies including prostate cancer.”
Taxotere is a drug in the taxane class of chemotherapy agents, which inhibits cancer-cell division by “freezing” the cell’s internal skeleton, which is comprised of microtubules. Microtubules assemble and disassemble during a cell cycle. Taxotere promotes their assembly and blocks their disassembly, thereby preventing cancer cells from dividing and resulting in cancer-cell death. Taxotere can help destroy cancer cells in the body when cancer is discovered, or recurs, after previous therapy.
The following list summarizes what researchers and scientists have concluded from studies of Taxotere and its effects on prostate cancer. Docetaxel is a semisynthetic chemotherapy drug made from an extract of needles of the yew tree. It is used to treat people with some types of early- and late-stage cancer.
Many chemotherapy drugs stop cancer cells from dividing by interfering with the cells’ DNA, but Taxotere acts quite differently. Taxotere changes microtubules, vital structures involved in cell division. Taxotere, one of the most effective anticancer chemotherapy drugs available, is injected into a vein to treat various types of tumors by attacking cancer cells. It is approved by the FDA to treat locally advanced or metastatic breast cancer that returns after any prior chemotherapy and locally advanced or metastatic non-small cell lung cancer that recurs after prior platinum-based chemotherapy.
Taxotere is given intravenously every 3 weeks, with each treatment lasting about an hour. In worldwide phase II clinical trials, Taxotere demonstrated the highest tumor response rates ever reported for a single agent in men with hormone-resistant disease.
Taxotere with Other Drugs
Clinical trials have suggested even more activity for regimens based on Taxotere. This agent is commercially available and is approved in the United States for the treatment of lung and breast cancer. Many oncologists now offer this drug in various combinations as first-line therapy against hormone-refractory prostate cancer. In initial studies as a single agent, Taxotere has demonstrated responses in nearly 50 percent of patients treated.
Although Taxotere has significant side effects, studies with a weekly schedule of therapy have demonstrated significant activity and less toxicity. Taxotere has been combined with estramustine in a number of clinical trials. These combinations have demonstrated the highest activity ever seen from chemotherapy against hormone-refractory prostate cancer. PSA responses have been seen in many patients. As many as 75 percent of patients receiving Taxotere-based combinations have had a 50 percent reduction in PSA, 43 percent have demonstrated a 75 percent reduction, and as many as 20 percent have demonstrated a complete normalization after therapy. In addition, patients receiving Taxotere-based combinations have also had a prolonged period before progression of PSA as well as significantly less pain.
Clinicians today are faced with the dilemma of which regimen to use. A recently concluded clinical trial compared the regimen of Novantrone plus steroids with Taxotere plus estramustine. These results should be available within the next several years. In the meantime, patients and physicians will need to consider the available clinical data and toxicities. From the patient’s perspective, there are at least two effective chemotherapy regimens, both of which have shown the ability to delay disease progression and improve the patient’s pain. Perhaps the sequential use of both regimens will lead to further improvements and perhaps an improvement in duration of survival as well.
Changing Your Mind about Chemotherapy
Developing hormone-refractory disease remains a serious complication for patients with prostate cancer. Recent clinical data do suggest a change in how these patients are treated. Prostate cancer is sensitive to chemotherapy with more than 50 percent of patients responding to newer combinations. Although patients with advanced disease have not been observed to live longer, it is reasonable to believe, based on other disease states, that earlier treatment might affect survival. Based on average survival rates of more than 20 months in hormone-refractory prostate cancer patients (whose average survival has historically been about 12 months), we are cautiously optimistic that a survival benefit will be seen in the randomized controlled trials that are being conducted.
Ongoing trials are evaluating the role of chemotherapy in asymptomatic patients with increasing PSA level as well as earlier in high-risk patients before or after initial local therapy in patients with hormone-sensitive disease. Available clinical trials do show the following: high response rates, prolonged survival in responders, palliation of pain, reduction in analgesic use, and improvements in quality of life. Although the benefits of chemotherapy in advanced hormone-refractory prostate cancer appear modest, the 68% response rate compares favorably to those documented in breast (48%), lung (15.3%), and colon (39%) cancer patients where chemotherapy as part of care is the standard.