Palliative and Supportive Care

Long-Term Toxicities of Selective Estrogen-Receptor Modulators and Antiaromatase Agents

May 1st 2003

Published literature indicates that the selective estrogen-receptormodulators (SERMs) tamoxifen and raloxifene (Evista) have favorableeffects on bone density, lipid profiles, and the incidence of secondbreast cancers, and unfavorable effects on the incidence of venousthrombosis and hot flushes. Tamoxifen increases the risk of endometrialcancer, but raloxifene does not. The effects of SERMs on sexualfunction and cognition are unclear. Because the selective antiaromataseagents are relatively new, the long-term effects of these agentson normal tissues are less well established. It appears that the nonsteroidalagents (anastrozole [Arimidex], letrozole [Femara]) and steroidal(exemestane [Aromasin]) antiaromatase agents may have differenteffects on normal tissues. Preliminary data demonstrate that anastrozoleincreases the risk of arthralgias and produces a decrease in bonedensity. In contrast, exemestane appears to favorably affect bonedensity and lipid profile, similar to tamoxifen and raloxifene. Theincidence of contralateral breast cancer is decreased in women onadjuvant anastrozole, but data for the other antiaromatase agents arenot yet available. Hot flushes have been reported with the use ofselective aromatase inhibitors, but their incidence seems to be comparableto what is reported with SERMs. Antiaromatase agents do notappear to cause venous thrombosis. More information about the effectsof the antiaromatase agents on normal tissue will become available asdata from ongoing adjuvant and chemoprevention trials are reported.Clinically, we should be conscious of the differences between antiaromataseagents and SERMs and their impact on women’s health.

Myalgias and Arthralgias Associated With Paclitaxel

February 1st 2003

Paclitaxel-induced myalgias and arthralgias occur in a significantfraction of patients receiving therapy with this taxane, potentiallyimpairing physical function and quality of life. Paclitaxel-inducedmyalgias and arthralgias are related to individual doses; associationswith the cumulative dose and infusion duration are less clear. Identificationof risk factors for myalgias and arthralgias could distinguisha group of patients at greater risk, leading to minimization of myalgiasand arthralgias through the use of preventive therapies. Optimalpharmacologic treatment and possibilities for the prevention of myalgiasand arthralgias associated with paclitaxel are unclear, partially dueto the small number of patients treated with any one medication. Theeffectiveness of nonsteroidal anti-inflammatory drugs (NSAIDs) is themost frequently documented pharmacologic intervention, although noclear choice exists for patients who fail to respond to NSAIDs. However,the increasing use of weekly paclitaxel could necessitate daily administrationof NSAIDs for myalgias and arthralgias and leave patients at riskfor adverse effects. This concern may also limit the use of corticosteroidsfor the prevention and treatment of paclitaxel-induced myalgias andarthralgias. Data from case reports suggest that gabapentin (Neurontin),glutamine, and, potentially, antihistamines (eg, fexofenadine [Allegra])could be used to treat and/or prevent myalgias and arthralgias. Giventhe safety profile of these medications, considerable enthusiasm existsfor evaluating their effectiveness in the prevention and treatment ofpaclitaxel myalgias and arthralgias, particularly in the setting ofweekly paclitaxel administration.