Loprinzi, Charles L.

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.

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.

Although chemotherapy‐induced neuropathy is perceived as a peripheral nervous system problem, data suggest that it may be ameliorated by addressing central nervous system functions. See also pages 1989–97.

253 Background: cPMP is chronic pain in the front thorax, axilla, and/or upper half of the arm beginning after mastectomy or lumpectomy persisting > 3 months after treatment and presents with pain, allodynia and disability. cPMP occurs in half of all patients with breast cancer and is severe in 13% (Gartner R JAMA 2009). Epidural bupivacaine, memantine, gabapentin or venlafaxine may help prevent cPMP, but there are no established proven treatments. (Shen J, Up to Date 2016) Scrambler therapy (ST) is an FDA-cleared treatment for neuropathic pain supported by multiple trials in over 800 patients with cancer pain, chemotherapy induced neuropathic pain, back pain, and post herpetic neuropathy (PHN). (Majithia N JSSC 2016) Methods: We treated 2 women with cPMP with standard ST, with repeated treatment if the pain returned. ST was done with ECG pads above and below the pain for 45 minutes daily, until pain resolved, and repeated if/when pain recurred. Results: Case 1: A 60 year-old woman had bilateral mastectomy 2 years prior with cPMP like “a barbed wire bra”. Before treatment, her pain was 8, which decreased to 0-2 after 5 treatments. Her pain returned 4 months later and was successfully retreated. She resumed a more normal life and was able to taper and eventually stop her opioids. Case 2: A 56 year-old woman had deep aching cPMP for a year following chemo, Mastectomy, and RT. Her pain was 10, decreased to 0-1/10. Her pain returned 1 month later; 3 treatments reduced her pain from 4/10 to 0/10 and improved her quality of life, which lasted for several months until cancer recurrence. Conclusions: Scrambler therapy successfully treated cPMP in 2 patients with improved pain and quality of life, and enabled one patient to stop her opioids in line with new CDC guidelines. Scrambler therapy appears to hold promise, as it does in chemotherapy-induced neuropathy, failed back syndrome, PHN, low back pain and other conditions; prospective trials are indicated to further evaluate this treatment modality. [Table: see text]

220 Background: Paclitaxel is associated with both an acute pain syndrome (P-APS) and chronic chemotherapy-induced peripheral neuropathy (CIPN). Preliminary animal data suggest that minocycline may be effective for the prevention of chemotherapy-induced neurotoxicity. The purpose of this pilot study was to investigate the efficacy of minocycline for the prevention of CIPN and P-APS. Methods: Patients with breast cancer were enrolled prior to initiating neoadjuvant or adjuvant weekly paclitaxel for 12 weeks. They were randomized to receive minocycline 200mg on day 1 followed by 100mg twice daily or a placebo, with the same dosing schedule. Patients completed (1) an acute pain syndrome questionnaire daily during chemotherapy, and (2) the EORTC QLQ-CIPN20 questionnaire at baseline, prior to each dose of paclitaxel, and monthly for 6 months post treatment. The primary goal was to obtain pilot data regarding the possible effect of minocycline on the prevention of paclitaxel-induced CIPN and P-APS, to determine if conducting a larger phase III placebo-controlled trial was indicated. Scores obtained from patient questionnaires were converted to a 0-100 scale, where higher scores = better quality of life. Results: Forty-seven patients were randomized, 45 of which were evaluable, with a mean age of 55. There were no remarkable differences noted between the two groups for the overall sensory score of the EORTC-CIPN 20 or its individual sub-questions, which evaluated tingling, numbness, or shooting burning pain in hands and feet. However, there was a significant difference in the daily average AUC pain score attributed to P-APS, favoring minocycline (median 96.0 vs 84.3; p = 0.02). Correspondingly, patients receiving minocycline used less opioid pain medications for control of P-APS (0% vs 23%, P = 0.05). Not only were no increased toxicities reported with minocycline, but there was an apparent improvement in fatigue (median AUC 76.7 vs 59.0; P = 0.02). Conclusions: Based on the results of this pilot study, minocycline did not appear to be beneficial for the prevention of CIPN, but did look promising for reducing P-APS. Further study of this effect may be warranted. Clinical trial information: NCT02297412.

176 Background: The purpose of the study was to determine the effectiveness of olanzapine (OLN) for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC). Methods: A randomized, double-blind, phase III trial was performed in chemotherapy-naïve patients receiving cisplatin, > 70 mg/m2, or cyclophosphamide-anthracycline-based chemotherapy, comparing OLN to placebo in combination with aprepitant (APR), a 5-HT3 receptor antagonist (5-HT3), and dexamethasone (DEX). The OLN regimen was 10 mg of oral OLN, 125 mg APR, a 5-HT3, and oral DEX 12 mg pre-chemotherapy, day 1, and 10 mg/day of oral OLN and 8 mg DEX on days 2-4 post-chemotherapy plus 80 mg APR on days 2, 3 post-chemotherapy. The placebo (PLA) regimen was oral placebo, pre-chemotherapy, day 1, and on days 2-4 post-chemotherapy; the APR, 5-HT3, and DEX pre- and post-chemotherapy were identical to that used in the OLN regimen. Fosaprepitant (150 mg IV), day 1 was allowed for substitution for the oral aprepitant. Palonosetron, ondansetron, or granisetron were the permitted 5-HT3 options. Nausea was measured on a 0-10 visual analogue scale, with 0 being “no nausea at all” and 10 being “nausea as bad as it can be”. No nausea was the primary endpoint and, complete response (no emesis and no use of rescue medications) was a secondary endpoint. Results: 401 patients (202 OLN, 199 PLA) were enrolled in the study. The proportion of patients who had no nausea was significantly greater for the OLN regimen compared to the PLA regimen for the acute period (24h post-chemotherapy) (74% vs. 45%, p < 0.0006), for the delayed period ( 24-120 h post-chemotherapy) (43% vs. 26%, p < 0.0006), and for the overall period (0-120 h) (39% vs. 22%, p < 0.0006). Complete response was significantly improved for the OLN patients compared to PLA patients for the acute (85% vs. 65%, p < 0.0001), the delayed (67% vs. 53%, p < 0.0078), and the overall periods (64% vs. 41%, p < 0.0001). There were no grade 3 or 4 toxicities. Conclusions: No nausea, the primary endpoint, and complete response, a secondary endpoint, were significantly improved with OLN, compared to PLA. Clinical trial information: NCT02116530.