Oncology Ny
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Review
The role of bisphosphonates in men with prostate cancer receiving androgen deprivation therapy.
Primary and secondary osteoporosis are prevalent in more than 2 million American men. One of the main causes of this is hypogonadism, in turn brought upon by early androgen deprivation therapy used in prostate cancer treatment. Androgen deprivation therapy produces a host of adverse effects on the skeleton, including an increase in bone turnover, a decrease in bone mineral density, and an increase in fracture risk. ⋯ Loss of bone due to androgen deprivation therapy is an important clinical issue for many men with prostate cancer, but osteoporosis is not an inevitable consequence of androgen deprivation therapy. Because of interpatient variations in peak bone mass as well as differences in rates of treatment-related bone loss, not all men with prostate cancer require treatment for osteoporosis. All men on androgen deprivation therapy should receive calcium and multivitamin supplements and should be considered for bisphosphonate therapy; this is particularly so for men with either a low baseline BMD or observed high rates of bone loss during androgen deprivation therapy.
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Gemcitabine (Gemzar) and paclitaxel show good activity as single agents and combined in metastatic breast cancer, and the combination of paclitaxel/trastuzumab (Herceptin) has been shown to prolong time to disease progression and survival significantly in this setting. Preclinical data indicate additive or synergistic effects of gemcitabine and trastuzumab in HER2-positive human breast cancer cell lines. In a phase II trial, patients with HER2-overexpressing metastatic breast cancer who had received no prior chemotherapy for metastatic disease received gemcitabine at 1,200 mg/m2 on days 1 and 8 and paclitaxel at 175 mg/m2 on day 1 every 21 days for six cycles plus trastuzumab at an initial loading dose of 4 mg/kg followed by 2 mg/kg weekly; patients without progressive disease after six cycles continued to receive trastuzumab until disease progression. ⋯ Median overall survival has not yet been reached, but is estimated at approximately 27 months. Significant toxicities apart from neutropenia were uncommon. The triplet combination of gemcitabine, paclitaxel, and trastuzumab is highly active and well tolerated in patients with HER2-overexpressing metastatic breast cancer.
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Hormonal treatment of advanced prostate cancer should be considered for patients who have stages C and D1 disease, a high risk of recurrence after local therapy, or prostate-specific antigen-measured recurrence after local treatment. This approach is dependent on most prostate cancer cells being androgen-dependent, but androgen-independent cells may arise after several years of hormonal therapy. ⋯ Convincing data do exist for the use of adjuvant/neoadjuvant hormonal therapy with external-beam radiation therapy. Although hormonal therapy is an important treatment modality for advanced prostate cancer, long-term treatment carries significant side effects that need to be considered.
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Published literature indicates that the selective estrogen-receptor modulators (SERMs) tamoxifen and raloxifene (Evista) have favorable effects on bone density, lipid profiles, and the incidence of second breast cancers, and unfavorable effects on the incidence of venous thrombosis and hot flushes. Tamoxifen increases the risk of endometrial cancer, but raloxifene does not. The effects of SERMs on sexual function and cognition are unclear. ⋯ Antiaromatase agents do not appear to cause venous thrombosis. More information about the effects of the antiaromatase agents on normal tissue will become available as data from ongoing adjuvant and chemoprevention trials are reported. Clinically, we should be conscious of the differences between antiaromatase agents and SERMs and their impact on women's health.