Deirdre R. Pachman

Chemotherapy-induced peripheral neuropathy: Prevention and treatment

Chemotherapy‐induced peripheral neuropathy (CIPN) is a common, dose‐limiting side effect of many chemotherapeutic agents. Although many therapies have been investigated for the prevention and/or treatment of CIPN, there is no well‐accepted proven therapy. In addition, there is no universally accepted, well‐validated measure for the assessment of CIPN. The agents for which there are the strongest preliminary data regarding their potential efficacy in preventing CIPN are intravenous calcium and magnesium (Ca/Mg) infusions and glutathione. Agents with the strongest supporting evidence for efficacy in the treatment of CIPN include topical pain relievers, such as baclofen/amitriptyline/ketamine gel, and serotonin and norepinephrine reuptake inhibitors, such as venlafaxine and duloxetine. Other promising therapies are also reviewed in this paper. Cutaneous electrostimulation is a nonpharmacological therapy that appears, from an early pilot trial, to be potentially effective in the treatment of CIPN. Finally, there is a lack of evidence of effective treatments for the paclitaxel acute pain syndrome (P‐APS), which appears to be caused by neurologic injury.

Troublesome Symptoms in Cancer Survivors: Fatigue, Insomnia, Neuropathy, and Pain

Patients with cancer suffer from a variety of symptoms associated with both cancer and its treatment. These symptoms may lead to a decreased quality of life for patients and can affect compliance with cancer therapies. The importance of adequately treating cancer-related symptoms is gaining more attention but, overall, many symptoms remain underdiagnosed and undertreated. Fatigue, insomnia, neuropathy, and pain are among the most common troublesome symptoms experienced by cancer survivors. This article will focus on the management of these symptoms, including an assessment of the current research and proposed best- management practices.

Management of menopause-associated vasomotor symptoms: Current treatment options, challenges and future directions

Hot flashes are one of the most common and distressing symptoms associated with menopause, occurring in more than 75% of postmenopausal women. They are especially problematic in breast cancer patients since some breast cancer therapies can induce hot flashes. For mild hot flashes, it is proposed that behavioral modifications are the first step in management. Hormonal therapies, including estrogens and progestogens, are the most well known effective agents in relieving hot flashes; however, the safety of these agents is controversial. There is an increasing amount of literature on nonhormonal agents for the treatment of hot flashes. The most promising data regard newer antidepressant agents such as venlafaxine, which reduces hot flashes by about 60%. Gabapentin is another nonhormonal agent that is effective in reducing hot flashes. While many complimentary therapies, including phytoestrogens, black cohosh, and dehydroepiandrosterone, have been explored for the treatment of hot flashes; none can be recommended at this time. Furthermore, there is a lack of strong evidence to support exercise, yoga, or relaxation for the treatment of hot flashes. Paced respirations and hypnosis appear to be promising enough to warrant further investigation. Another promising nonpharmacological therapy, currently under investigation, involves a stellate ganglion block.

Clinical Course of Oxaliplatin-Induced Neuropathy: Results From the Randomized Phase III Trial N08CB (Alliance)

PURPOSE Given that the clinical course of oxaliplatin-induced neuropathy is not well defined, the current study was performed to better understand clinical parameters associated with its presentation. METHODS Acute and chronic neuropathy was evaluated in patients receiving adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin) on study N08CB (North Central Cancer Treatment Group, Alliance). Acute neuropathy was assessed by having patients complete daily questionnaires for 6 days with each cycle of FOLFOX. Before each dose of FOLFOX and as long as 18 months after chemotherapy cessation, chronic neurotoxicity was assessed with use of the 20-item, European Organisation for Research and Treatment of Cancer quality-of-life questionnaire for patients with chemotherapy-induced peripheral neuropathy. RESULTS Three hundred eight (89%) of the 346 patients had at least one symptom of acute neuropathy with the first cycle of FOLFOX; these symptoms included sensitivity to touching cold items (71%), sensitivity to swallowing cold items (71%), throat discomfort (63%), or muscle cramps (42%). Acute symptoms peaked at day 3 and improved, although they did not always resolve completely between treatments. These symptoms were about twice as severe in cycles 2 through 12 as they were in cycle 1. For chronic neurotoxicity, tingling was the most severe symptom, followed by numbness and then pain. During chemotherapy, symptoms in the hands were more prominent than they were in the feet; by 18 months, symptoms were more severe in the feet than they were in the hands. Patients with more severe acute neuropathy during the first cycle of therapy experienced more chronic sensory neurotoxicity (P < .0001). CONCLUSION Acute oxaliplatin-induced neuropathy symptoms do not always completely resolve between treatment cycles and are only half as severe on the first cycle as compared with subsequent cycles. There is a correlation between the severities of acute and chronic neuropathies.

Management options for established chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a variety of chemotherapeutic agents. Clinicians are cognizant of the negative impact of CIPN on cancer treatment outcomes and patients’ psychosocial functioning and quality of life. In an attempt to alleviate this problem, clinicians and patients try various therapeutic interventions, despite limited evidence to support efficacy of these treatments. The rationale for such use is mostly based on the evidence for the treatment options in non-CIPN peripheral neuropathy syndromes, as this area is more robustly studied than is CIPN treatment. In this manuscript, we examine the existing evidence for both CIPN and non-CIPN treatments and develop a summary of the best available evidence with the aim of developing a practical approach to the treatment of CIPN, based on available literature and clinical practice experience.

Randomized clinical trial of imiquimod: An adjunct to treating cervical dysplasia

OBJECTIVES Human papillomavirus (HPV) infection is a major risk factor for cervical cancer. Imiquimod is a topical medication that enhances the immune response to HPV-induced genital warts. This study evaluated cervical application of imiquimod as an adjunct to standard treatment for cervical dysplasia. STUDY DESIGN Fifty-six patients were randomized to standard excisional/ablative treatment vs applications of imiquimod followed by standard treatment. The primary endpoint was dysplasia recurrence within 2 years. RESULTS There were no differences in dysplasia recurrence between the 2 groups. Treatment was well tolerated, with side effects being mild but significantly worse in women receiving imiquimod for, chills, fatigue, fever, headache, myalgias, and vaginal discharge. CONCLUSION This trial does not support the hypothesis that imiquimod, as used in this trial, has an impact on recurrence of cervical dysplasia, but the adequacy of findings are limited by sample size. The trial does support the feasibility and acceptability of the use of imiquimod on the cervix.

Therapeutic Strategies for Cancer Treatment Related Peripheral Neuropathies

Opinion statementChemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity associated with multiple chemotherapeutic agents. CIPN may have a detrimental impact on patients’ quality of life and functional ability, as well as result in chemotherapy dose reductions. Although symptoms of CIPN can improve with treatment completion, symptoms may persist. Currently, the treatment options for CIPN are quite limited. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, has the most evidence supporting its use in the treatment of CIPN. Other agents with potential benefit for the treatment of established CIPN include gabapentinoids, venlafaxine, tricyclic antidepressants, and a topical gel consisting of the combination of amitriptyline, ketamine, and baclofen; none of these, however, has been proven to be helpful and ongoing/future studies may well show that they are not beneficial. The use of these agents is often based on their efficacy in the treatment of non-CIPN neuropathic pain, but this does not necessarily mean that they will be helpful for CIPN-related symptoms. Other nonpharmacologic interventions including acupuncture and Scrambler therapy are supported by positive preliminary data; however, further larger, placebo-controlled trial data are needed to confirm or refute their effectiveness.

Scrambler Therapy for the management of chronic pain

PurposeChronic 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.MethodsThe 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.ResultsTo 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.ConclusionThe 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.

Clinical Trials in Integrative Therapies

OBJECTIVES To review clinical trials in natural products and mind-body therapies for oncology symptom management, to discuss issues related to developing clinical trials in this area, and outline examples of rigorous and innovative study design. DATA SOURCES Peer reviewed literature. CONCLUSION Most of the evidence for the integrative therapies reviewed is derived from phase II trials, and is considered preliminary. More research is needed in these therapies to clearly articulate their role in the management of oncology symptoms. Innovative strategies and methodologies for studying integrative therapies have been demonstrated. IMPLICATIONS FOR NURSING PRACTICE It is necessary to critically evaluate the literature to be able to educate patients about integrative therapies. Investigators should expand on well-designed studies that demonstrate clinically important effects. Dissemination trials may be a good strategy, once data exists, to move integrative therapies into the care of patients.

Sternal skin conductance: a reasonable surrogate for hot flash measurement?

Objective This study aims to examine the accuracy of a new sternal skin conductance (SSC) device in measuring hot flashes and to assess the acceptability of the device by women. Methods Three small descriptive pilot studies were performed using two sequential prototypes of the SSC device developed by an engineering device company in the Midwest. The devices were worn either in a monitored setting for 24 hours or in an ambulatory setting for 5 weeks. During the study period, women recorded hot flashes in a prospective hot flash diary and answered questions about the acceptability of wearing the SSC device. Results The first prototype was not able to collect any analyzable skin conductance data owing to various malfunction issues, including poor conductance and battery failure. However, 16 women wore the device for 5 weeks and reported that wearing the device was acceptable, although 31% stated that it interfered with daily activities. Hot flash data from the second prototype revealed a 24% concordance rate between self-reported and device-recorded hot flashes. Conclusions Findings from these studies support discordance between device-recorded and self-reported hot flashes. In addition, the studies reveal further limitations of SSC monitoring, including difficulties with data collection and lack of consistency in interpretation. Based on these results and other recent trials identifying issues with SSC methodology, it is time to find a better physiologic surrogate measure for hot flashes.