Prostate cancer was the second cancer shown to be responsive to hormonal manipulation. The treatment of choice for patients with metastatic prostate cancer is elimination of testosterone production by the testes through either surgical or chemical castration. Bilateral orchiectomy or estrogen therapy in the form of diethylstilbestrol was previously used as first-line therapy. Presently, the use of luteinizing hormone-releasing hormone (LHRH) agonists—including leuprolide and goserelin agonists, alone or in combination with an antiandrogen (eg, flutamide, bicalutamide, or nilutamide)— is the preferred approach (see Chapter 40). There appears to be no survival advantage of total androgen blockade using a combination of LHRH agonist and antiandrogen agent compared with single-agent therapy. Abiraterone, an inhibitor of steroid synthesis (see Chapter 39), has recently been approved. Hormonal treatment reduces symptoms—especially bone pain—in 70–80% of patients and may cause a significant reduction in the prostate-specific antigen (PSA) level, which is now widely accepted as a surrogate marker for response to treatment in prostate cancer. Although initial hormonal manipulation is able to control symptoms for up to 2 years, patients usually develop progressive disease. Second-line hormonal therapies include aminoglutethimide plus hydrocortisone, the antifungal agent ketoconazole plus hydrocortisone, or hydrocortisone alone.
Unfortunately, nearly all patients with advanced prostate cancer eventually become refractory to hormone therapy. A regimen of mitoxantrone and prednisone is approved in patients with hormone-refractory prostate cancer because it provides effective palliation in those who experience significant bone pain. Estramustine is an antimicrotubule agent that produces an almost 20% response rate as a single agent. However, when used in combination with either etoposide or a taxane such as docetaxel or paclitaxel, response rates are more than doubled to 40–50%. The combination of docetaxel and prednisone was recently shown to confer survival advantage when compared with the mitoxantroneprednisone regimen, and this combination has now become the standard of care for hormone-refractory prostate cancer.
Colorectal cancer (CRC) is the most common type of gastrointestinal malignancy. Nearly 150,000 new cases are diagnosed each year in the USA; worldwide, nearly 1.2 million cases are diagnosed annually. At the time of initial presentation, only about 40–45% of patients are potentially curable with surgery. Patients presenting with high-risk stage II disease and stage III disease are candidates for adjuvant chemotherapy with an oxaliplatin-based regimen in combination with 5-FU plus leucovorin (FOLFOX) or with oral capecitabine (XELOX) and are generally treated for 6 months following surgical resection. Treatment with this combination regimen reduces the recurrence rate after surgery by 35% and clearly improves overall patient survival compared with surgery alone.