Loprinzi, Charles

PURPOSE The primary objective of this randomized, double-blind, placebo-controlled, multicenter phase II study (Alliance A221805) was to screen two doses of duloxetine for preventing sensory oxaliplatin-induced peripheral neuropathy (OIPN). METHODS Participants were randomly assigned 1:1:1 to receive once daily 30 mg duloxetine, 60 mg duloxetine, or placebo. Eligible participants had stage II to III colorectal cancer and no baseline neuropathy, had Eastern Cooperative Oncology Group performance status 0-2, were age 25 years and older, and received oxaliplatin via one of the following doses and schedules: 85 mg/m 2 every 2 weeks (6 or 12 doses) or 130 mg/m 2 every 3 weeks (4 doses). Duloxetine/placebo was taken once daily beginning day 1 of cycle 1 and continued for 17 weeks. The primary end point, a composite response reflecting sensory OIPN symptom severity and onset, was measured in weeks 19-21 using a validated participant-reported outcome survey assessing extremity numbness, tingling, and pain. Response was defined as a participant-reported highest score of ≤2 (ie, 1 = not at all; 2 = a little) on survey items. To be evaluable for the response end point, eligible participants must have initiated oxaliplatin and submitted ≥1 postbaseline OIPN survey. RESULTS Of the 199 participants (n = 66, 30 mg duloxetine; n = 66, 60 mg duloxetine; n = 67, placebo), 46, 47, and 50 (N = 143, 71.8%), respectively, were evaluable for primary end point analysis based on modified intention-to-treat criteria. Participant mean age was 55.1 years (standard deviation = 10.4). Most were White (n = 113, 80.7%) and male (n = 82, 58.6%). The proportion of responders among those receiving placebo (68.0%) was similar to those receiving duloxetine 30 mg (65.2%) or 60 mg (66.0%). Duloxetine adherence rates, measured via pill counts—30 mg (54%), 60 mg (57%), and placebo (59%) groups—were low (<75%). CONCLUSION Duloxetine is not more promising than placebo for preventing sensory OIPN.

Background: Mu opioid receptors (MORs) in peripheral tissues mediate adverse effects of opioids that impair health-related quality of life (HRQoL) and may stimulate cancer progression via mitogenic signaling. Naloxegol, a peripherally acting MOR antagonist (PAMORA), is approved for opioid-induced constipation. Safety and efficacy of naloxegol have not been evaluated concurrently with systemic cancer therapy. Methods: We conducted a randomized, double-blind, placebo-controlled trial of naloxegol in patients with advanced lung adenocarcinoma starting first-line systemic therapy. Results: Only 50 patients were enrolled; the trial was terminated early due to slow accrual. Two of the three components of the feasibility primary endpoint were not met (accrual and PRO completion). At 6 months, FACT-L emotional well-being was better with naloxegol (p = 0.0113). There were trends towards better Trial Outcome Index (p = 0.0505) and physical well-being (p = 0.0628) with naloxegol. Bowel function favored naloxegol for constipation (p = 0.0223), rectal pain during defecation (p = 0.0075), and abdominal pain from constipation (p = 0.0113). Adverse event frequency and severity, PRO-CTCAE, urinary hesitancy, pain scores, and progression-free and overall survival were comparable between naloxegol and placebo. Conclusions: Naloxegol appears to be safe and tolerable, with a signal of improved HRQoL and previously unappreciated benefit for emotional well-being, without adverse clinical outcomes. Our findings should be confirmed in larger studies. ClinicalTrials.gov ID: NCT03087708.

PURPOSE Over 50% of households in the United States have at least one musician—many musicians are also breast cancer survivors. This group has not been well studied, and given the level of fine sensory-motor skill required for musicianship, we hypothesized that musicians experience unique manifestations of breast cancer treatment toxicities. METHODS A nine-item Musical Toxicity Questionnaire (MTQ) was distributed to patients who had consented to participate in the Mayo Clinic Breast Cancer Registry. The MTQ screened participants by asking if they played a musical instrument or sang in the last 10 years: questions populated for those who answered yes. Respondents were asked if they noticed difficulty with their musical endeavor during or after breast cancer treatment, defined as acute musical toxicity (AMT). The questionnaire asked which side effect and cancer-directed therapy most influenced musical ability, what musical attributes were affected, and the timeline of resolution. Multivariable and classification tree analyses assessed relationships between AMT and treatment characteristics. RESULTS Of 1,871 survey respondents, 29% (535/1,871) self-identified as musicians. Over a quarter (27%, 144/535) reported AMT, and for 57% (82/144), AMT had not resolved at the time of survey. Of the treatments each participant received, chemotherapy was most often reported as most negatively impactful (63/89 who received chemotherapy, 71%). Decreased endurance was the most common musical difficulty (64% of those with AMT, 92/144), followed by decreased accuracy, trouble playing/singing quickly, and difficulty using proper technique. Multivariable and classification tree analyses revealed that receipt of chemotherapy was most strongly correlated with AMT. CONCLUSION These results will help oncology care teams counsel musicians, answer questions about impacts on musicality, and provide a timeline for resolution of musical symptoms.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) from oxaliplatin and taxane drugs is a bothersome toxicity. Palmitoylethanolamide (PEA) has been reported to improve myelinated nerve fiber function in patients experiencing painful CIPN. We conducted a double-blind, placebo-controlled, randomized trial of PEA in patients with established CIPN. Methods: Eligible patients were adults who had pain, numbness, tingling, or other symptoms of CIPN for at least three months following completion of paclitaxel, oxaliplatin, or cisplatin-based chemotherapy. Study patients were randomized to one of the two treatment groups (PEA versus placebo, both administered either once or twice daily). The CIPN20 questionnaire was assessed weekly. Results: A total of 17 males and 71 females participated in the study; most had neuropathy from paclitaxel. Most (85%) finished 8 weeks of treatment. There was no suggestion that either of the PEA arms did any better than the combined placebo arms. There was no signal of significant toxicity differences between the three study arms. Quality of life outcome measures were similar between the study arms, as were cognitive function evaluations. Discussion: PEA failed to improve established CIPN. Future trials might explore whether PEA may be effective in preventing CIPN or cognitive changes based on data that suggest it may be helpful in this situation. Conclusions: PEA failed to improve established chemotherapy-induced neuropathy.

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual . The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. See the Appendix for disclaimers and other important information ( Appendix 1 and Appendix 2 , online only).

AbstractIntroductionNasal symptoms are frequently reported by patients undergoing chemotherapy.MethodsEligible patients planning to receive paclitaxel, docetaxel, nab‐paclitaxel, bevacizumab without a concomitant taxane, or “other” (non‐taxane, non‐bevacizumab) chemotherapy regimens were invited to participate in this prospective study. Patients reported nasal symptoms prior to each dose of chemotherapy.ResultsThe percentage of patients (95% CI) who reported nasal symptoms was the same for patients who received bevacizumab or nab‐paclitaxel, 82.6% (61.2%, 95.1%). There were no significant differences among the proportions of patients experiencing nasal symptoms within the paclitaxel, nab‐paclitaxel, and bevacizumab cohorts. Patients in the nab‐paclitaxel cohort were more likely to experience symptoms than those in the non‐taxane non‐bevacizumab cohort or docetaxel cohort (p = 0.001, p = 0.001). Patients in the bevacizumab cohort were more likely to experience nasal symptoms than those in the non‐taxane non‐bevacizumab cohort (p = 0.03).ConclusionNasal vestibulitis symptoms are common in patients receiving chemotherapy, especially those receiving paclitaxel, docetaxel, and bevacizumab. Further investigations into treatments of this symptom complex are warranted.

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 .

While oxaliplatin-induced peripheral neuropathy (OIPN) is more common and severe in patients who receive the previous standard, 6-month oxaliplatin-based treatment, we hypothesized that OIPN was still pervasive in patients who received shorter, 3-month-treatment regimens. Using six EORTC QLQ-CIPN20 questions that quantify numbness (N), tingling (T) and shooting/burning pain (P) in upper/lower distal extremities, our aim is to quantify patient-reported responses over 3 months (6 cycles) of oxaliplatin regarding symptom-specific timing, location and severity. For each question, patients were asked how each of the sensory symptoms had affected them during the preceding week, with 1 = “Not at all”, 2 = “A little”, 3 = “Quite a bit” and 4 = “Very much”. The proportional odds model for the cumulative log odds of response that allowed symptom-specific patient heterogeneity to be obtained was applied to a pooled dataset from the placebo arms of two multisite OIPN prevention trials and fit separately to the upper/lower distal extremities. For each symptom, we report the cycle-specific marginal probabilities for each response. In 141 patients, substantial patient heterogeneity in the likelihood, at a given cycle, of a more severe response for a symptom was present. Distinct patterns in the probabilities for each response over time for N and T were observed between the upper/lower distal extremities, while the probabilities of a response >1 for P was largely negligible in both locations. Despite the decrease in exposure to oxaliplatin from 6 to 3 months, OIPN was still pervasive with patients experiencing considerable N and T in the fingers (or hands) and toes (or feet).

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.

Background Lymphedema is an adverse effect of breast cancer treatment that causes swelling and pain in the arm and hand. We tested 2 lymphedema prevention interventions and their impact on health‐related quality of life (HRQOL) in a group‐randomized trial at 38 cooperative group sites within the United States. Methods Patients were recruited before breast surgery. Sites were randomly assigned to education‐only (EO) lymphedema prevention or education plus exercise and physical therapy (LEAP). Lymphedema was defined as a ≥10% difference in arm volume at any time from baseline to 18 months postsurgery. HRQOL was assessed using the Functional Assessment of Cancer Therapy–Breast plus 4 lymphedema items (FACT‐B+4). Longitudinal mixed model regression analysis, adjusting for key demographic and clinical variables, examined participants' HRQOL by intervention group and lymphedema status. Results A total of 547 patients (56% LEAP) were enrolled and completed HRQOL assessments. The results revealed no differences between the interventions in preventing lymphedema ( P = .37) or HRQOL (FACT‐B+4 total score; P = .8777). At 18 months, the presence of lymphedema was associated with HRQOL at borderline significance ( P = .0825). However, African American patients reported greater lymphedema symptoms ( P = .0002) and better emotional functioning ( P = .0335) than patients of other races or ethnicities. Lower HRQOL during the intervention was associated with younger age ( P ≤ .0001), Eastern Cooperative Oncology Group performance status >0 ( P = .0002), ≥1 positive lymph nodes ( P = .0009), having no education beyond high school ( P < .0001), having undergone chemotherapy ( P = .0242), and having had only axillary node dissection or sentinel node biopsy versus both ( P = .0007). Conclusion The tested interventions did not differ in preventing lymphedema or in HRQOL outcomes. African American women reported greater HRQOL impacts due to lymphedema symptoms than women of other races or ethnicities.