Hot flashes are very common in women in menopause and can have a detrimental effect on quality of life. Women on risk reduction therapy are particularly prone because treatments, such as tamoxifen, raloxifene, or oophorectomy, have the potential to exacerbate these symptoms. Hormonal treatments, despite the fact that they represent the most effective therapies, are not used for the treatment of hot flashes in these women because of concerns that they may increase the risk for breast cancer. As a result, several nonhormonal therapies have been tested in randomized placebo-controlled trials and shown to be effective, such as paroxetine, venlafaxine, desvenlafaxine, fluoxetine, citalopram, gabapentin, and pregabalin. In addition, several nonpharmacologic therapies have been tested with various successes. An additional consideration is how some of those drugs, especially fluoxetine and paroxetine, interact with the metabolism of tamoxifen. This article discusses these issues, and provides some recommendations regarding use of nonhormonal therapies for treating hot flashes in women on risk reduction therapy, with an emphasis on pharmacogenomic considerations.
Kostandinos Sideras and Charles L. Loprinzi
Charles L. Loprinzi and Peter M. Ravdin
Decisions regarding the use of adjuvant cytotoxic and hormonal therapies for women with breast cancer ideally should be made jointly by the patient and oncologist. For patients to be adequately involved in this decision-making process, they must be provided with appropriate education regarding the potential benefits and risks of adjuvant therapies. The recommended steps for doing this are: 1) understand baseline prognosis with locoregional therapy (surgery, radiation, or both) alone for the individual patient at hand; 2) determine the estimated benefit afforded by adjuvant therapy options for the individual patient; 3) estimate the risk of side effects of adjuvant therapy options; 4) convey the above information to the individual patient; 5) facilitate the individual patient's decision regarding adjuvant systemic therapy; and 6) support the patient's decision. Two computer-based tools (Numeracy and Adjuvant!) are available to facilitate this process.
Deirdre R. Pachman, Kathryn Ruddy, Lindsey R. Sangaralingham, Axel Grothey, Nilay D. Shah, Andreas S. Beutler, Joleen M. Hubbard, and Charles L. Loprinzi
Substantial research efforts have focused on methods of treating and preventing oxaliplatin-associated neuropathy, the dose-limiting toxicity associated with this drug. Administration of intravenous calcium and magnesium (CaMg) before and after oxaliplatin has been the most studied approach to preventing oxaliplatin-induced neuropathy. Although early reports demonstrated potential benefit, subsequent larger trials failed to confirm the efficacy of CaMg in preventing this adverse effect. This article explores how accumulating evidence for and against the use of CaMg for preventing oxaliplatin-induced neuropathy has impacted clinical practice.
Ciara C. O'Sullivan, Holly K. Van Houten, Lindsey R. Sangaralingham, Alexis D. Leal, Shivani Shinde, Hongfang Liu, David Ettinger, Charles L. Loprinzi, and Kathryn J. Ruddy
Purpose: Prevention of chemotherapy-induced nausea and vomiting is essential to preserve quality of life in patients with cancer receiving highly emetogenic chemotherapy (HEC). Recently, new drugs (eg, fosaprepitant, and the newer neurokinin-1 receptor antagonists [NK1RAs] rolapitant and netupitant) and updated antiemetic guidelines have emerged. However, trends in real-world antiemetic use are understudied. Methods: We identified patients treated with an initial dose of HEC (either cisplatin or doxorubicin/cyclophosphamide) from January 2006 to June 2016 using administrative claims data from a US commercial insurance database (OptumLabs). Antiemetic use was determined by identifying intravenous/oral/transdermal administration within ±1 day of the chemotherapy dose and/or prescription fill from 14 days before to 7 days after chemotherapy. We used descriptive statistics to present patient demographics, chemotherapy drugs administered, presence/absence of a central intravenous access device, and antiemetics used. Results: A total of 23,030 patients (67.3%) received doxorubicin/cyclophosphamide and 11,206 (32.7%) received cisplatin. Dexamethasone and 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs) were consistently used by 85% to 95% of patients, consistent with guideline recommendations. NK1RAs were underused early on, but use increased to approximately 80% in the most recently evaluated year. Fosaprepitant use increased precipitously starting in 2009, preceding a sharp decrease in aprepitant use beginning in 2011. Receipt of olanzapine, rolapitant, and netupitant was minimal throughout the study period. Conclusions: Dexamethasone and 5-HT3RAs were used by most patients receiving HEC, in accordance with guideline recommendations. NK1RA use was less adherent with guidelines.
Robert W. Carlson, Elizabeth Brown, Harold J. Burstein, William J. Gradishar, Clifford A. Hudis, Charles Loprinzi, Eleftherios Paul Mamounas, Edith A. Perez, Kathleen Pritchard, Peter Ravdin, Abram Recht, George Somlo, Richard L. Theriault, Eric P. Winer, Antonio C. Wolff, and for the NCCN Adjuvant Therapy for Breast Cancer Task Force
The National Comprehensive Cancer Network (NCCN) first published the NCCN Breast Cancer Treatment Guidelines in 1996. The Guidelines address the treatment of all stages of breast cancer across the spectrum of patient care and have been updated yearly. Adjuvant therapy for breast cancer has undergone an especially rapid evolution over the past few years. Therefore, the NCCN Breast Cancer Guidelines Panel was supplemented by additional experts to form the Adjuvant Therapy Task Force to provide a forum for an extended discussion and expanded input to the adjuvant therapy recommendations for the Breast Cancer Treatment Guidelines. Issues discussed included methods of risk-stratification for recurrence; how biologic markers such as HER2 status, quantitative estrogen receptor, or genetic markers can be incorporated as prognostic or predictive factors; and how age, menopausal status, and estrogen receptor levels impact benefits from chemotherapy and endocrine therapy. Additionally, the task force discussed the strategies for use of aromatase inhibitors in postmenopausal women and the potential incorporation of trastuzumab into adjuvant therapy of women with HER2/neu positive breast cancer. This supplement summarizes the background data and ensuing discussion from the Adjvuant Task Force meeting. (JNCCN 2006;4[suppl 1]:S-1–S-26)