Systemic Therapy

Systemic Therapy


The use of bisphosphonates to reduce skeletal morbidity in patients with bone metastases should be considered.[19] Results of randomized trials of pamidronate and clodronate in patients with bony metastatic disease show decreased skeletal morbidity.[20-22][Level of evidence: 1iC] Zoledronate has been at least as effective as pamidronate.[23] (Refer to the PDQ summary on Pain for more information on bisphosphonates.)

Hormone therapy

Hormone therapy should generally be considered as initial treatment for a postmenopausal patient with newly diagnosed metastatic disease if the patient’s tumor is ER-positive, PR-positive, or ER/PR-unknown. Hormone therapy is especially indicated if the patient’s disease involves only bone and soft tissue and the patient has either not received adjuvant antiestrogen therapy or has been off such therapy for more than 1 year. While tamoxifen has been used in this setting for many years, several randomized trials suggest equivalent or superior response rates and progression-free survival (PFS) for the aromatase inhibitors compared to tamoxifen.[24-26][Level of evidence: 1iiDiii] In a meta-analysis that included randomized trials in patients who were receiving an aromatase inhibitor as either their first or second hormonal therapy for metastatic disease, those who were randomly assigned to a third-generation drug (anastrozole, letrozole, exemestane, or vorozole) lived longer (hazard ratio [HR] for death = 0.87; 95% confidence interval [CI], 0.82–0.93) than those who received standard therapy (tamoxifen or a progestational agent).[27][Level of evidence: 1iA]

Several randomized but underpowered trials have tried to determine if combined hormone therapy (luteinizing hormone-releasing hormone [LHRH] agonists + tamoxifen) is superior to either approach alone in premenopausal women. Results have been inconsistent.[28-30] The best study design compared buserelin (an LHRH agonist) versus tamoxifen versus the combination in 161 premenopausal women with hormone receptor–positive tumors.[31] Patients receiving buserelin and tamoxifen had a significantly improved median survival of 3.7 years compared with those receiving tamoxifen or buserelin who survived 2.9 and 2.5 years, respectively (P = .01).[31][Level of evidence: 1iiA] Very few women in this trial received adjuvant tamoxifen, which makes it difficult to assess whether these results are applicable to women who relapse after adjuvant tamoxifen.

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