A pilot randomized, placebo-controlled, double-blind study of omega-3 fatty acids to prevent paclitaxel-associated acute pain syndrome in breast cancer patients: Alliance A22_Pilot2.

PURPOSE: Paclitaxel is associated with an acute pain syndrome (P-APS- and chronic chemotherapy-induced peripheral neuropathy (CIPN). P-APS is associated with higher risk of CIPN. Omega-3 fatty acids have well-established anti-inflammatory and neuroprotective properties. The primary purpose of this pilot study was to assess whether omega-3 fatty acids could decrease P-APS and thus CIPN. METHODS: Patients scheduled to receive weekly paclitaxel for breast cancer were randomized to receive 4 g of omega-3 acid ethyl esters (Lovaza) or placebo, beginning 1 week prior and continued until paclitaxel was stopped. Patients completed acute pain questionnaires at baseline, daily after each treatment, and 1 month after completion of therapy. RESULTS: Sixty patients (49 evaluable) were randomized to treatment versus placebo. Seventeen (68.0%) patients receiving the omega-3 fatty acids intervention experienced P-APS, compared to 15 (62.5%) of those receiving placebo during the first week of treatment (p = 0.77). Over the full 12-week study, 21 (84.0%) patients receiving the omega-3 fatty acid intervention experienced P-APS, compared to 21 (87.5%) of those receiving placebo (p = 1.0). Secondary outcomes suggested that those in the intervention arm used more over-the-counter analgesics (OR: 1.65, 95% CI: 0.72-3.78, p = 0.23), used more opiates (OR: 2.06, 95% CI: 0.55-7.75, p = 0.28), and experienced higher levels of CIPN (12.8, 95% CI: 7.6-19.4 vs. 8.4, 95% CI: 4.6-13.2, p = 0.21). CONCLUSIONS: The results of this pilot study do not support further study of the use of omega-3 fatty acids for the prevention of the P-APS and CIPN. TRIAL REGISTRATION: Number: NCT01821833.

Dietary supplement use and recommendations for discontinuation in an integrative oncology clinic.

PURPOSE: This project evaluated the dietary supplement (DS) use of patients referred to an integrative oncology program and documented the frequency and reasons for recommending stopping DS. Many patients with cancer are taking dietary supplements and may not disclose such to their care teams. There is potential for harm in several ways: (1) interactions with their medications that may increase side effects, (2) interactions with their treatment that may lead to decreased efficacy, and 3) direct toxicity from the supplement. METHODS: Patient data (N = 100) were collected prospectively from an Integrative Oncology Clinic. The number and type of DS were documented. Using the Natural Medicines Database, we determined whether supplements interacted with the patient's other medications or cancer therapies. We calculated the percentage of patients in which a recommendation for discontinuation (DC) of DS was provided, along with the supporting reasons. RESULTS: We found that 91% of patients took DS, averaging 5.5 per patient (range 0-20). In 35% of patients, we recommended stopping some of their DS or other therapies, the reasons being: DC antioxidants, vitamin B12/iron while on chemo/RT (unless deficient or part of protocol) 32%; DC due to taking excess amounts (i.e., fat-soluble vitamins, calcium, iron) 13.5%; DC supplements with known toxicity (i.e., laetrile, Miracle mineral solution) 13.5%; DC due to interactions with other medications (i.e., anticoagulants) 13.5%; DC DS with potential to increase cancer growth (i.e., estrogenic potential in those with hormone-sensitive cancers, glutamine) 11%; DC due to potential for increased toxicity with chemotherapy (i.e., increased risk of bleeding, CIPN) 11%; DC probiotics, immune stimulants, and cannabis while on immunotherapy 5.4%. CONCLUSIONS: Patients with cancer referred to an integrative oncology clinic use large numbers of DS with the potential for adverse effects and/or decreasing efficacy of treatments. This study highlights the prevalence of DS usage in cancer patients referred to an integrative oncology clinic and demonstrates the need for counseling about safe supplement use.

Integrative Medicine for Pain Management in Oncology: Society for Integrative Oncology-ASCO Guideline.

PURPOSE: The aim of this joint guideline is to provide evidence-based recommendations to practicing physicians and other health care providers on integrative approaches to managing pain in patients with cancer. METHODS: The Society for Integrative Oncology and ASCO convened an expert panel of integrative oncology, medical oncology, radiation oncology, surgical oncology, palliative oncology, social sciences, mind-body medicine, nursing, and patient advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2021. Outcomes of interest included pain intensity, symptom relief, and adverse events. Expert panel members used this evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 227 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS: Among adult patients, acupuncture should be recommended for aromatase inhibitor-related joint pain. Acupuncture or reflexology or acupressure may be recommended for general cancer pain or musculoskeletal pain. Hypnosis may be recommended to patients who experience procedural pain. Massage may be recommended to patients experiencing pain during palliative or hospice care. These recommendations are based on an intermediate level of evidence, benefit outweighing risk, and with moderate strength of recommendation. The quality of evidence for other mind-body interventions or natural products for pain is either low or inconclusive. There is insufficient or inconclusive evidence to make recommendations for pediatric patients. More research is needed to better characterize the role of integrative medicine interventions in the care of patients with cancer.Additional information is available at https://integrativeonc.org/practice-guidelines/guidelines and www.asco.org/survivorship-guidelines.

Topical Cannabinoids for Treating Chemotherapy-Induced Neuropathy: A Case Series.

BACKGROUND: Chemotherapy-induced peripheral neuropathy is a common and often severe side effect from many chemotherapeutic agents, with limited treatment options. There is no literature on the use of topical cannabinoids for chemotherapy-induced neuropathy. CASE PRESENTATIONS: The current manuscript presents a case series of patients presenting in oncology clinics at Sutter Health, CA and Mayo Clinic, Rochester, MN from April 2019 to December 2020 with chemotherapy-induced peripheral neuropathy who used topical creams containing the cannabinoids delta-nine-tetrahydrocannabinol (THC) and/or cannabidiol (CBD). CONCLUSIONS: This case series suggests that topical cannabinoids may be helpful for patients with chemotherapy-induced peripheral neuropathy. This paper also discusses the potential mechanisms of action by which topical cannabinoids might alleviate established CIPN symptoms. A randomized placebo-controlled trial using a standardized product is planned to study the actual efficacy of such treatment.

Real-World Experiences With Yoga on Cancer-Related Symptoms in Women With Breast Cancer.

PURPOSE: Integrative therapies such as yoga are potential treatments for many psychological and physical symptoms that occur during and/or after treatment for cancer. The purpose of the current study was to evaluate the patient-perceived benefit of yoga for symptoms commonly experienced by breast cancer survivors. METHODS: 1,049 breast cancer survivors who had self-reported use of yoga on a follow up survey, in an ongoing prospective Mayo Clinic Breast Disease Registry (MCBDR), received an additional mailed yoga-focused survey asking about the impact of yoga on a variety of symptoms. Differences between pre- and post- scores were assessed using Wilcoxon Signed Rank Test. RESULTS: 802/1,049 (76%) of women who were approached to participate, consented and returned the survey. 507/802 (63%) reported use of yoga during and/or after their cancer diagnosis. The vast majority of respondents (89.4%) reported some symptomatic benefit from yoga. The most common symptoms that prompted the use of yoga were breast/chest wall pain, lymphedema, and anxiety. Only 9% of patients reported that they had been referred to yoga by a medical professional. While the greatest symptom improvement was reported with breast/chest wall pain and anxiety, significant improvement was also perceived in joint pain, muscle pain, fatigue, headache, quality of life, hot flashes, nausea/vomiting, depression, insomnia, lymphedema, and peripheral neuropathy, (all p-values <0.004). CONCLUSION: Data supporting the use of yoga for symptom management after cancer are limited and typically focus on mental health. In this study, users of yoga often reported physical benefits as well as mental health benefits. Further prospective studies investigating the efficacy of yoga in survivorship are warranted.

Randomized Trial of Scrambler Therapy for Chemotherapy-Induced Peripheral Neuropathy: Crossover Analysis.

CONTEXT: Preliminary trials report that Scrambler Therapy, a form of electroanalgesia, may improve discomfort from chemotherapy-induced peripheral neuropathy (CIPN). OBJECTIVE: The objective of this phase II, randomized controlled trial was to evaluate the efficacy of Scrambler therapy vs. transcutaneous electrical nerve stimulation (TENS) in treating CIPN. METHODS: Fifty patients were accrued for the first half of this two-part, crossover trial consisting of a 2-week treatment period with either Scrambler or TENS, followed by an 8-week observation period, and then crossover treatment. Twenty-two patients proceeded to the crossover phase. The primary means of assessment was patient-reported outcomes, including symptom severity scales and Global Impression of Change questionnaires. Symptoms were assessed daily during the treatment period and weekly during an 8-week observation period. RESULTS: A 50% or greater reduction in primary symptom (pain or tingling) score on the last day of treatment was achieved by 6 of 10 Scrambler-treated patients (60%) and 3 of 12 TENS-treated patients (25%) after crossover (P = 0.11). By day 4 of treatment, the two arms diverged with respect to mean change in primary symptom score; this effect was largely carried through to the end of the two-week treatment period. Similarly, Scrambler therapy appeared better than TENS when assessed by Global Impression of Change for neuropathy, pain, and overall quality of life. CONCLUSIONS: Similar findings from the initial randomization and crossover phases of this study support further evaluation of the efficacy of Scrambler therapy in alleviating CIPN symptoms. Evaluation in a larger, randomized controlled trial with standardized treatment is warranted.

Real-world experiences with acupuncture among breast cancer survivors: a cross-sectional survey study.

PURPOSE: The purpose of this study was to evaluate acupuncture use among breast cancer survivors, including perceived symptom improvements and referral patterns. METHODS: Breast cancer survivors who had used acupuncture for cancer- or treatment-related symptoms were identified using an ongoing prospective Mayo Clinic Breast Disease Registry (MCBDR). Additionally, Mayo Clinic electronic health records (MCEHR) were queried to identify eligible participants. All received a mailed consent form and survey including acupuncture-related questions about acupuncture referrals, delivery, and costs. Respondents were also asked to recall symptom severity before and after acupuncture treatment and time to benefit on Likert scales. RESULTS: Acupuncture use was reported among 415 participants (12.3%) of the MCBDR. Among MCBDR and MCEHR eligible participants, 241 women returned surveys. A total of 193 (82.1%) participants reported a symptomatic benefit from acupuncture, and 57 (24.1% of participants) reported a "substantial benefit" or "totally resolved my symptoms" (corresponding to 4 and 5 on the 5-point Likert scale). The mean symptom severity decreased by at least 1 point of the 5-point scale for each symptom; the percentage of patients who reported an improvement in symptoms ranged from 56% (lymphedema) to 79% (headache). The majority of patients reported time to benefit as "immediate" (34%) or "after a few treatments" (40.4%). Over half of the participants self-referred for treatment; 24.1% were referred by their oncologist. Acupuncture delivery was more frequent in private offices (61.0%) than in hospital or medical settings (42.3%). Twelve participants (5.1%) reported negative side effects, such as discomfort. CONCLUSIONS: Acupuncture is commonly utilized by patients for a variety of breast cancer-related symptoms. However, patients frequently self-refer for acupuncture treatments, and most acupuncture care is completed at private offices, rather than medical clinic or hospital settings.

A randomized phase II trial evaluating two non-pharmacologic interventions in cancer survivors for the treatment of sleep-wake disturbances: NCCTG N07C4 (Alliance).

PURPOSE: Sleep disturbance is a prevalent problem for cancer survivors and effective behavioral treatments are not widely used for this population. This study evaluated home-based sleep interventions based on cognitive behavioral therapy for insomnia (CBT-I). METHODS: This phase II randomized controlled trial evaluated two manualized interventions over 7 weeks. The intervention group received sleep hygiene information, stimulus control, sleep restriction, and a bedtime imagery audio recording. The control group was similar, but without sleep restriction and used audio recordings of bedtime short stories instead of imagery. Eligibility included adult cancer survivors who had trouble falling asleep or falling back to sleep on 3 of 7 days. Patients with diagnoses of sleep or mental health disorders were excluded. The primary endpoint was change in time to fall asleep or falling back to sleep after awakening, from baseline to week 7. Two-sample T tests evaluated differences between arms for this endpoint. RESULTS: Ninety-three of 168 planned participants were enrolled from 20 institutions. The study closed early for poor accrual. Baseline time to sleep was 45 min and 52 min for the intervention and control group, respectively. At 7 weeks, both groups improved, the intervention group to 26 min and control group to 30 min, a non-significant difference between groups (p = 0.85). Secondary outcomes improved in both groups with no significant differences between arms. CONCLUSIONS: Improvement in sleep outcomes in both arms was consistent with other CBT-I interventions delivered through alternative approaches to provider-delivered therapy. More research on optimal scalable delivery of CBT-I is needed. CLINICAL RELEVANCE: This study supports the effectiveness of CBT-I based behavioral interventions for sleep but also the need for better delivery methods to improve uptake and effect size. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00993928.

Scrambler therapy for chemotherapy neuropathy: a randomized phase II pilot trial.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a prominent clinical problem, with limited effective therapies. Preliminary non-randomized clinical trial data support that Scrambler Therapy is helpful in this situation. METHODS: Patients were eligible if they had CIPN symptoms for at least 3 months and CIPN-related tingling or pain at least 4/10 in severity during the week prior to registration. They were randomized to receive Scrambler Therapy versus transcutaneous electrical nerve stimulation (TENS) for 2 weeks. Patient-reported outcomes (PROs) were utilized to measure efficacy and toxicity daily for 2 weeks during therapy and then weekly for 8 additional weeks. RESULTS: This study accrued 50 patients, 25 to each of the 2 study arms; 46 patients were evaluable. There were twice as many Scrambler-treated patients who had at least a 50% documented improvement during the 2 treatment weeks, from their baseline pain, tingling, and numbness scores, when compared with the TENS-treated patients (from 36 to 56% compared with 16-28% for each symptom). Global Impression of Change scores for "neuropathy symptoms," pain, and quality of life were similarly improved during the treatment weeks. Patients in the Scrambler group were more likely than those in the TENS group to recommend their treatment to other patients, during both the 2-week treatment period and the 8-week follow-up period (p < 0.0001). Minimal toxicity was observed. CONCLUSIONS: The results from this pilot trial were positive, supporting the conduct of further investigations regarding the use of Scrambler Therapy for treating CIPN.

Rose geranium in sesame oil nasal spray: a treatment for nasal vestibulitis?

OBJECTIVES: As a rose geranium in sesame oil spray product has been anecdotally noted to improve nasal vestibulitis symptoms, this study was designed to assess whether patients with nasal vestibulitis associated with cancer-directed therapy experienced symptomatic improvements from it. METHODS: Patients with breast cancer, prescribed rose geranium nasal spray, were identified by looking at pharmacy records and patient diagnosis at Mayo Clinic Rochester. Patient medical information, as well as documentation of symptoms, were gleaned from medical charts. Questionnaires were sent to patients regarding their experiences. RESULTS: Of the 40 patients with breast cancer who were prescribed rose geranium nasal spray, 100% were receiving cancer-directed therapy: 58 % were receiving taxane chemotherapy; others received a variety of cytotoxic and targeted therapy treatments. Twenty patients who had used the spray product returned surveys. Patient-reported nasal symptoms included bleeding (90%), dryness (86%), pain (81%), scabbing (67%) and sores (52%); patients consistently reported symptoms at a higher proportion than did healthcare providers. All patients who used the rose geranium nasal spray reported symptomatic benefit; one reported a little benefit, 11 (55%) reported moderate benefit and eight (40%) reported dramatic or complete resolution of symptoms. The therapy was well tolerated in most patients. CONCLUSIONS: Rose geranium in sesame oil nasal spray appears to improve patient-reported nasal symptoms associated with cancer-directed therapy.

Impaired Postural Control and Altered Sensory Organization During Quiet Stance Following Neurotoxic Chemotherapy: A Preliminary Study.

Individuals diagnosed with chemotherapy-induced peripheral neuropathy (CIPN) demonstrate impaired balance and carry an increased risk of falling. However, prior investigations of postural instability have only compared these individuals against healthy controls, limiting the understanding of impairments associated with CIPN. Therefore, the purpose of this study was to better isolate postural control impairments that are associated with CIPN. Twenty cancer survivors previously diagnosed with breast or colorectal cancer participated. Participants were separated into 3 groups: no prior chemotherapy exposure (CON, n = 6), and recent treatment with taxane- or oxaliplatin-based chemotherapy with no/mild symptoms of CIPN (-CIPN, n = 8) or moderate/severe symptoms of CIPN (+CIPN, n = 6). Postural control was assessed by measuring center of pressure during standing balance conditions that systematically interfered with somatosensory, visual, and/or vestibular information. The presence of CIPN sensory symptoms was associated with impaired postural control, particularly during eyes-closed balance conditions ( P < .05). Additionally, medial-lateral postural instability was more pronounced in the +CIPN group compared with the -CIPN group and CON participants ( P < .05). Greater postural instability during eyes-closed balance in individuals with CIPN is consistent with impaired peripheral sensation. Balance impairments in cancer survivors with CIPN demonstrate the unique challenges in this population and motivate the need for targeted efforts to mitigate postural control deficits that have previously been associated with fall risk.

Randomized placebo-controlled pilot trial of omega 3 fatty acids for prevention of aromatase inhibitor-induced musculoskeletal pain.

PURPOSE: Aromatase inhibitor (AI)-induced joint symptoms negatively impact drug adherence and quality of life in breast cancer survivors. Mechanisms underlying symptoms may include inflammation. It is hypothesized that n - 3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and may reduce symptoms. METHODS: We conducted a randomized, double-blind, placebo-controlled study comparing 4.3 g/day n - 3 PUFA supplements vs placebo for 24 weeks in postmenopausal breast cancer patients starting adjuvant AIs. Primary endpoints were adherence and tolerability; secondary outcomes included inflammatory cytokines and symptoms assessed by the Brief Pain Inventory short form (BPI-SF) and Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) at 0, 12, and 24 weeks. RESULTS: Forty-four women were randomized, of which 35 completed the study. Adherence was ≥ 88% based on these 35 patients with pill counts as well as change in red blood cell (RBC) n - 3 PUFAs. Common toxicities included grade 1 flatulence (55% of both groups) and belching (45% of n - 3 group). Mean pain severity scores (BPI-SF) did not change significantly by time or treatment arm. Quality of life, based on FACT-ES scores, significantly decreased within placebo (p = 0.04), but not the n - 3 group (p = 0.58), with a trend toward between-group differences (p = 0.06) at 12 weeks, but no significant differences at 24 weeks. RBC n - 3 levels were strongly positively correlated with FACT-ES at 12 weeks, but attenuated at 24 weeks. CONCLUSION: High-dose n - 3 PUFA supplementation is feasible and well tolerated when administered with AIs. Additional studies are needed to evaluate efficacy in prevention of joint symptoms.

Scrambler Therapy for the management of chronic pain.

PURPOSE: Chronic pain is a widespread and debilitating condition, encountered by physicians in a variety of practice settings. Although many pharmacologic and behavioral strategies exist for the management of this condition, treatment is often unsatisfactory. Scrambler Therapy is a novel, non-invasive pain modifying technique that utilizes trans-cutaneous electrical stimulation of pain fibers with the intent of re-organizing maladaptive signaling pathways. This review was conducted to further evaluate what is known regarding the mechanisms and mechanics of Scrambler Therapy and to investigate the preliminary data pertaining to the efficacy of this treatment modality. METHODS: The PubMed/Medline, SCOPUS, EMBASE, and Google Scholar databases were searched for all articles published on Scrambler Therapy prior to November 2015. All case studies and clinical trials were evaluated and reported in a descriptive manner. RESULTS: To date, 20 reports, of varying scientific quality, have been published regarding this device; all but one small study, published only as an abstract, provided results that appear positive. CONCLUSION: The positive findings from preliminary studies with Scrambler Therapy support that this device provides benefit for patients with refractory pain syndromes. Larger, randomized studies are required to further evaluate the efficacy of this approach.

Longitudinal adverse event assessment in oncology clinical trials: the Toxicity over Time (ToxT) analysis of Alliance trials NCCTG N9741 and 979254.

BACKGROUND: Traditional methods of reporting adverse events in clinical trials are inadequate for modern cancer treatments with chronic administration. Conventional analysis and display of maximum grade adverse events do not capture toxicity profiles that evolve over time or longer lasting, lower grade toxic effects; we aimed to address this shortcoming in this study. METHODS: We developed an analytic approach and standardised, comprehensive format, the Toxicity over Time (ToxT) approach, which combines graphs and adverse event tabular displays with multiple longitudinal statistical techniques into a readily applicable method to study toxic effects. Plots visualising summary statistics or individual patient data over discrete timepoints were combined with statistical methods including the following longitudinal techniques: repeated measures models that describe the changes in adverse events across all cycles of treatment; time-to-event analyses of first and worst grade toxicity; and area under the curve (AUC) analyses summarising adverse event profiles over the entire course of a study, including chronic low-grade events. We applied ToxT analysis to adverse event data from two completed North Central Cancer Treatment Group (NCCTG/Alliance) trials: N9741 (NCT00003594), in which different combinations of oxaliplatin, 5-fluorouracil, and irinotecan were investigated for metastatic colorectal cancer, and 979254, in which survivors of breast cancer were given venlafaxine or placebo for control of hot flashes. FINDINGS: In trial NCCTG 979254 there was a higher incidence of late-occurring dry mouth in patients who were given venlafaxine than in those given placebo (week 1 [baseline]: 13% [six incidence in 48 patients, SD 5] vs 22% [11/49, SD 6]; p=0·20; week 5: 49% [24/49, 7] vs 2% [1/46, 2]; p<0·0001). In trial NCCTG N9741 there was an increased incidence of early nausea for patients given irinotecan plus oxaliplatin (IROX) compared with those given 5-fluorouracil plus oxaliplatin (FOLFOX; cycle 1 mean grade nausea 1·1 [SD 1·0] vs 0·6 [0·7]; p<0·0001). Event charts showed earlier occurrences of higher grades of diarrhoea for patients given IROX compared with those given FOLFOX, and the AUC analysis shows a higher magnitude of diarrhoea consistently over time throughout the study in patients given IROX versus those given FOLFOX (mean AUC 4·2 [SD 5·2] vs 2·9 [4·2]; p<0·0001). INTERPRETATION: The ToxT analytical approach incorporates the dimension of time into adverse event assessment and offers a more comprehensive depiction of toxic effects than present methods. With new, continuously administered targeted agents, immunotherapy, and maintenance regimens, these improved longitudinal analyses are directly relevant to patients and are crucial in cancer clinical trials. FUNDING: National Cancer Institute of the National Institutes of Health and the Mayo Comprehensive Cancer Center.

Efficacy and Safety of Rivaroxaban in Patients with Venous Thromboembolism and Active Malignancy: A Single-Center Registry.

OBJECTIVE: The purpose of this study is to evaluate the efficacy and safety of rivaroxaban in patients with venous thromboembolism and active malignancy, given the paucity of clinical data with the use of direct Xa inhibitors in this high-risk population. PATIENTS AND METHODS: Consecutive patients treated with rivaroxaban for deep vein thrombosis or pulmonary embolism, enrolled into Mayo Thrombophilia Clinic Direct Oral Anticoagulants Registry between March 1, 2013, and April 30, 2015, were followed prospectively to evaluate the efficacy and safety of this therapy. RESULTS: Of the 404 venous thromboembolism patients in the registry, 296 received rivaroxaban and had at least 3 months of follow-up. Of these, 118 (40%) had active malignancy (51% female, mean age 66 ± 10 years) and 178 had no cancer (47% female, mean age 55 ± 15 years). The 3 most common cancer locations were genitourinary (23.6%), gastrointestinal (20.3%), and lung (13.5%). There was no difference in venous thromboembolism recurrence between the malignant (3.3%) and the nonmalignant (2.8%) venous thromboembolism groups (P = .533). Borderline higher rates for major bleeding (P = .06) and nonmajor clinically relevant bleeding (P = .08) were observed in patients with cancer. CONCLUSIONS: The "real world" effectiveness and safety of rivaroxaban is similar for venous thromboembolism patients with and without active malignancy.

Phase II evaluation of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes.

PURPOSE: Hot flashes are a significant source of symptom burden that negatively impacts quality of life (QOL). For women who have contraindications to, or are unwilling to consider, estrogens or antidepressants for bothersome hot flashes, there are limited effective pharmacologic or complementary and alternative medicines. METHODS: This single-arm phase II trial studied the efficacy of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes. Eligible women were required to have reported ≥14 hot flashes per week for ≥1 month. The patients were treated with SAMe at a dose of 400 mg twice daily to evaluate whether a reduction in hot flash score appeared to be better than the historical placebo response of approximately 25%. The women kept a daily hot flash diary during a baseline week and then daily during weeks 2-7. The primary endpoint was the change from baseline to week 7 in hot flash score and hot flash frequency. Secondary endpoints included toxicity analyses and the effect of SAMe on QOL. RESULTS: From October 28, 2010 to January 30, 2012, 43 women were treated with SAMe. The decrease in mean percent of baseline hot flash score and frequency was 35.4 and 32.6%, respectively. When compared to the historical placebo response of 25%, the effect of SAMe on hot flash score was not statistically significant (p = 0.09). Treatment was well tolerated with expected grade 1/2 gastrointestinal toxicity and no negative effect on QOL. CONCLUSIONS: The use of SAMe does not appear to significantly reduce hot flashes more than would be expected with a placebo.

Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy: a 5-year follow-up.

PURPOSE: This study was designed to explore whether zoledronic acid could prevent expected loss of bone mineral density (BMD) in postmenopausal women with pre-existing osteopenia or osteoporosis who were initiating adjuvant letrozole therapy for primary breast cancer. METHODS: Between June 2006 and July 2007, 60 postmenopausal women with estrogen and/or progesterone receptor-positive breast cancer and a BMD T-score ≤-2.0 were enrolled. Participants received letrozole 2.5 mg and vitamin D 400 IU daily, calcium 500 mg twice daily, and zoledronic acid 4 mg every 6 months for a maximum of 5 years or until disease progression. BMD at the lumbar spine and femoral neck was recorded at the start of the study and annually for 5 years. Patients were evaluated for fractures every 6 months for the duration of the trial. RESULTS: After 5 years, mean BMD increased significantly by 11.6% (p = 0.01) at the lumbar spine and by 8.8% (p = 0.01) at combined sites. Femoral neck BMD increased by 4.2%, although this was not significant (p = 0.23). At the end of the trial, BMDs were consistent with osteoporosis in 7 % and osteopenia in 36% of the patients. A total of six fractures were reported after 417 individual assessments. CONCLUSIONS: Zoledronic acid appears to prevent further bone loss in postmenopausal breast cancer patients with osteopenia and osteoporosis starting treatment with letrozole. These findings were maintained at 5 years and support concurrent initiation of bisphosphonate and aromatase inhibitor therapy in this high-risk population.