Chemotherapy & Targeted Therapy
Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs, and can be administered through a vein, injected into a body cavity, or delivered orally in the form of a pill. Chemotherapy is different from surgery or radiation therapy in that the cancer-fighting drugs circulate in the blood to parts of the body where the cancer may have spread and can kill or eliminate cancers cells at sites great distances from the original cancer. As a result, chemotherapy is considered a systemic treatment.
Chemotherapy is currently used mainly in men with advanced prostate cancer. The chemotherapy drug docetaxel was demonstrated to improve survival of men with metastatic prostate cancer in 2004 and has remained the mainstay of chemotherapy often utilized in combination with other chemotherapy drugs. For people who have cancers that respond well to chemotherapy, this approach helps treat their cancer effectively, enabling them to enjoy full, productive lives. Importantly, many side effects once associated with chemotherapy are now easily prevented, controlled, or avoided altogether by using targeted therapies allowing many people to work, travel, and participate in many of their other normal activities while receiving treatment. In a study conducted by researchers at the Dana-Farber Cancer Institute, Taxotere® (docetaxel) administered with androgen-deprivation therapy to metastatic prostate cancer patients was found to extend overall survival by more than 13 months. The results were reported at the 2014 American Society of Clinical Oncology (ASCO) meeting held in Chicago. The study included 790 men with hormone-sensitive metastatic prostate cancer. Patients were randomized to standard ADT or to ADT plus Taxotere, a chemotherapy drug. The primary endpoint of the study was overall survival. Due to a statistically significant survival difference observed between the two cohorts at an interim analysis, the trial was ended prematurely. After 29 months, 136 patients in the control arm had died, while 101 patients in the ADT plus Taxotere group had died. Men in the ADT/Taxotere arm had a median overall survival rate of 57.6 months; those in the ADT-only arm had a median overall survival of 44 months. Other markers of the disease—prostate-specific antigen (PSA) response, time to castration resistance, and time to progression prostate were also improved in the ADT/Taxotere cohort. For men with a high disease burden at the beginning of the study, the survival difference was even greater: a median overall survival of 49.2 months versus 32.2 months.1, 2
A Targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Treatments that “target” cancer cells may offer the advantage of reduced treatment-related side effects and improved outcomes. Advances in science and technology have led to the development of several different drugs for the treatment of prostate cancer over the past few years and doctors are working to determine the best sequence, combinations, and timing of utilization.
- Abiraterone (Zytiga®)
- Enzalutamide (Xtandi®)
- sipuleucel-T (Provenge®)
- Cabazitaxel (Jevtana®)
- Treatment of Bone Complications
- Zoledronic acid (Zometa®)
- Denosumab (Xgeva™)
- Radium Ra 223 dichloride (Xofigo®)
Cabazitaxel is administered intravenously and has been demonstrated to improve time to cancer progression and overall survival in men with HRPC previously treated with docetaxel. Cabazitaxel’s primary side effect is neutropenia, and it is recommended that patients receive a white blood cell growth factor if they are at high risk of this complication.3
Sipuleucel-T is actually an immunotherapy that prompts the body’s immune system to respond against the cancer. A Phase III clinical trial that contributed to the FDA approval of sipuleucel-T was a study known as IMPACT (Immunotherapy for Prostate AdenoCarcinoma Treatment) which demonstrated an improvement in overall survival for men treated with sipuleucel-T. The main side effects reported were chills, fever, and headache.4
Treatment of Bone Complications
Patients with advanced prostate cancer can have cancer cells that have spread to their bones, called bone metastases. Bone metastases commonly cause pain, increase the risk of fractures, and can lead to a life-threatening condition characterized by an increased amount of calcium in the blood called hypercalcemia. Treatments for bone complications may include drug therapy or radiation therapy.
Zoledronic acid (Zometa®)
Zoledronic acid is a bisphosphonate drug and this class of drugs can effectively prevent loss of bone that occurs from cancer that has spread to the bones thereby reducing the risk of fractures, and decreasing pain. Bisphosphonate drugs work by inhibiting bone resorption, or breakdown. Zoledronic acid may be used to reduce the risk of complications from bone metastases or to treat cancer-related hypercalcemia,
Denosumab targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Studies have suggested that Denosumab may be more effective than Zoledronic acid at delaying bone complications in prostate cancer patients with bone metastases. Denosumab is associated with side effects including hypocalcemia (low levels of calcium in the blood) and osteonecrosis of the jaw (death of bone in the jaw).5
Xofigo® (radium Ra 223 dichloride)
Radium 223 is a targeted radiopharmaceutical agent that binds with minerals in the bone to deliver radiation directly to bone tumors, thereby limiting the damage to the surrounding normal tissues. The U.S. Food and Drug Administration (FDA) approved the drug in May 2013 after a trial known as Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) was stopped early after an interim analysis showed that treatment with significantly improved survival.6
Additional Information About Chemotherapy & Targeted Therapy
Tannock I, de Wit R, Berry W, et al.Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. New England Journal of Medicine. 2004; 351:1502-1512.
2 Petrylak D, Tangen C, Hussain M, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. New England Journal of Medicine. 2004; 351:1513-1520.
3 de Bono JS, Oudard S, Ozguroglu M et al: Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomized open-label trial. Lancet 2010; 376: 1147.
4 Kantoff PW, Higano CS, Shore ND et al: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363: 411.
5 Smith MR, Saad F, Coleman R et al. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. Early online publication November 16, 2011.
6 Michalski J, Sartor O, Parker C, et al. Radium-223 dichloride (Ra-223) impact on skeletal-related events, external-beam radiotherapy (EBRT), and pain in patients with castration-resistant prostate cancer (CRPC) with bone metastases: Updated results from the phase III ALSYMPCA trial. Proceedings of the 55th Annual Meeting of the American Society of Radiation Oncology. International Journal of Radiation Oncology Biology Physics. 2013; 87(2): S108-S109. Abstract 265.