Abstract
Introduction: Different non-pharmacological interventions have been studied to manage symptoms derived from chemotherapy, but their effectiveness is unknown. Objective: To describe non-pharmacological interventions for managing symptoms secondary to antineoplastic chemotherapy in adults. Materials and Methods: Systematic review of analytical experimental and observational studies (2021 to 2023). The studies were selected, and data was extracted in parallel. Discrepancies were resolved with a third reviewer. The risk of bias was assessed using the Risk of Bias (RoB) tool and The Newcastle-Ottawa Scale (NOS). The literature was synthesized descriptively based on prioritized outcomes. Results: The prioritized outcomes were neutropenia, pain, neuropathy, nausea, vomiting, alopecia, anorexia, and sleep disorders. Out of 7520 references found, 62 were included for analysis. Acupressure showed a possible effect in controlling symptoms such as nausea and vomiting. The intervention with cold on the scalp showed differences in the stages of alopecia severity. Other interventions showed heterogeneity. Discussion: Non-pharmacological interventions have been widely described in observational and experimental studies in the control of side effects of chemotherapy; however, there is homogeneity and a high risk of bias. Conclusion: Acupressure, muscle massage, music therapy, foot baths, and other interventions have been studied for nausea, vomiting, sleep disorders, neutropenia, alopecia, anorexia, pain, and neuropathy as secondary symptoms prioritized by patients. It is necessary to standardize both the interventions and how measure the outcomes.
Keywords: Complementary Therapies; Drug-Related Side Effects and Adverse Reactions; Integrative Oncology; Signs and Symptoms.
Resumen
Introducción: Diferentes intervenciones no farmacológicas se han estudiado para manejar los síntomas derivados de la quimioterapia, pero se desconoce su efectividad. Objetivo: Describir las intervenciones no farmacológicas para el manejo de síntomas secundarios a la quimioterapia antineoplásicaenadultos. Materiales y Métodos:Revisión sistemática deestudios experimentales y observacionales analíticos (2021 a 2023). La selección de estudios y extracción de datos se realizó de forma paralela. Las discrepancias se resolvieron con un tercer revisor. Se evaluó el riesgo de sesgo con las herramientas Risk Of Bias (RoB) y The Newcastle-Ottawa Scale (NOS). La síntesis de la literatura se realizó de forma descriptiva por desenlace priorizado. Resultados: Los desenlaces priorizados fueron neutropenia, dolor, neuropatía, náuseas, vomito, alopecia, anorexia y desordenes del sueño. Se encontraron 7520 referencias, 62 incluidas para el análisis. La acupresión mostró un posible efecto en el control de síntomas como las náuseas y vomito. La intervención con frio en el cuero cabelludo mostro diferencias en los estadios de la severidad de alopecia. Las otras intervenciones mostraron heterogeneidad. Discusión: Las intervenciones no farmacológicas han sido ampliamente descritas en estudios observaciones y experimentales en el control de efecto secundarios a la quimioterapia, sin embargo, existe homogeneidad, y alto riesgo de sesgo. Conclusión: Acupresión, masaje muscular, musicoterapia, baño de pies entre otros son las intervenciones que se han estudiado para náuseas, vomito, desordenes del sueño, neutropenia, alopecia, anorexia, dolor y neuropatía como síntomas secundarios priorizados por pacientes. Se requiere estandarizar tanto las intervenciones como la forma de medición de los desenlaces.
Palabras Clave: Terapias Complementarias; Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos; Oncología integrativa; Signos y Síntomas.
Resumo
Introdução: Diferentes intervenções não farmacológicas têm sido estudadas para o manejo dos sintomas decorrentes da quimioterapia, mas sua eficácia é desconhecida. Objetivo: Descrever intervencóes náo farmacológicas para o manejo dos sintomas secundários a quimioterapia antineoplásica em adultos. Materiais e Métodos: Revisáo sistemática de estudos analíticos experimentais e observacionais (2021 a 2023). A selecáo dos estudos e a extracáo dos dados foram realizadas paralelamente. As discrepáncias foram resolvidas com um terceiro revisor. O risco de viés foi avaliado por meio das ferramentas Risk Of Bias (RoB) e Newcastle-Ottawa Scale (NOS). A síntese da literatura foi realizada de forma descritiva por desfecho priorizado. Resultados: Os desfechos priorizados foram neutropenia, dor, neuropatia, náuseas, vómitos, alopecia, anorexia e distúrbios do sono. Foram encontradas 7.520 referéncias, 62 incluídas para análise. A acupressáo mostrou possível efeito no controle de sintomas como náuseas e vómitos. A intervencáo fria no couro cabeludo mostrou diferencas nos estágios de gravidade da alopecia. As demais intervencóes apresentaram heterogeneidade. Discussáo: Intervencóes não farmacológicas têm sido amplamente descritas em estudos observacionais e experimentais no controle dos efeitos colaterais da quimioterapia, porém há homogeneidade e alto risco de viés; Conclusáo: Acupressáo, massagem muscular, musicoterapia, escalda-pés, entre outras, sáo as intervencóes que tém sido estudadas para náuseas, vómitos, distúrbios do sono, neutropenia, alopecia, anorexia, dor e neuropatia como sintomas secundários priorizados pelos pacientes. É necessário padronizar tanto as intervencóes quanto a forma de medir os resultados.
Palavras-Chave: Terapias Complementares; Efeitos Colaterais e Reacóes Adversas Relacionados a Medicamentos; Oncologia Integrativa; Sinais e Sintomas.
Introduction
In 2020, Globocan reported 19,292,789 new cancer cases worldwide1. Specific treatment regimens have been studied for each type of disease, with chemotherapy being the main intervention2. The incidence of side effects is reported to be 70-80% due to the involvement of rapidly growing cells3. There is evidence of side effects such as nausea, vomiting, alopecia, mucositis, fatigue, constipation, neutropenia, and mood changes, which affect a person's quality of life4,5. Treatment plans include medications to control these symptoms; however, these medications can trigger other secondary symptoms that further impact the quality of life6.
Integrative oncology, in coordination with evidence-based complementary therapies and conventional cancer care, improves patients' quality of life and clinical outcomes. This orientation empowers patients' participation in their treatment'. It has been reported that approximately 50% of cancer patients use complementary and alternative medicine (CAM), and in patients with advanced disease, the prevalence of CAM use can reach 100%7.
The evidence shows a wide variety ofnon-pharmacological interventions, which presents a challenge to the caregiver when seeking symptom control. This process involves balancing pharmacological treatment, complementation with non-pharmacological interventions, and individual preferences8. This review aims to synthesize the existing evidence on non-pharmacological interventions to control the side effects of chemotherapy, as prioritized by patients and healthcare professionals.
Materials and Methods
The protocol was published in the International Prospective Register of Systematic Reviews (PROSPERO CRD4202017212) and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA, 2009) guidelines; the analysis database was stored in Mendeley Data10. We included randomized clinical trials (RCTs) and longitudinal analytic observational studies conducted in adults with cancer undergoing treatment that described non-pharmacological interventions to control chemotherapy-related side effects. Studies were only included in the review if the nonpharmacological interventions were delivered by trained personnel. Descriptive studies, cost-effectiveness studies, conference proceedings, systematic reviews, meta-analyses, clinical practice guidelines, letters to the editor, or studies with unanalyzable data or without reported measures of effect, animal studies, or studies in pregnant women were excluded.
Outcome selection and prioritization
The outcomes were prioritized according to the preferences of patients and health professionals at the time of making a decision about an intervention, including the list described in the literature3,11. Ten cancer experts and chemotherapy patients from a university hospital oncology department were independently asked to prioritize each side effect on a scale of 1 to 9, with 7 to 9 being critical, 4 to 6 being important, and 1 to 3 being of limited importance (according to the GRADE approach12). For this review, outcomes with scores greater than 8 were included (Figure 1).
Search strategy
The electronic databases PubMed/MEDLINE, Ovid Embase, LILACS/Bireme, The Cochrane Library, and Epistemonikos were searched from March 2021 to May 2023. University repositories and reference lists of included studies were also searched. Authors and clinical experts in cancer were also contacted to inquire about possible published studies in this area. The search algorithm was developed using free search terms and the Medical Subject Headings (MeSH) (Table 1).
Study selection and data extraction
Two groups of reviewers (Group 1 - MEG-N and ABP; Group 2 - LI/EP and OC) independently screened references found by title and abstract according to the RAYYAN eligibility criteria for systematic reviews13. Two reviewers read full texts for final inclusion. Disagreements were resolved with the assistance of a third reviewer (AB-L). A matrix was created in Microsoft Excel® in which two independent reviewers entered data including authors, year of publication, study's country of origin, sex, cancer diagnosis, comorbidities, sample size, study population, non-pharmacological intervention used, and measure of the effect in both the experimental and control groups. The authors were contacted to request information on missing data.
Risk of bias assessment
Figures 2A, B, C, D, E, and E show the graphical visualization of the risk of bias for experimental studies assessed with the RoB-2 tool. Figure 2G shows the risk of bias assessment for analytic observational cohort studies assessed with the Newcastle-Ottawa Scale (NOS) (Figure 2).
Synthesis of evidence
Study characteristics were described narratively by outcome. The heterogeneity of the studies was assessed by clinical observation of the population, outcomes and their measurement, and description of the intervention performed10.
Results
A total of 7,520 references were found, of which 237 were selected for full-text reading. Sixty-two references were included between 1988 and 2023 (Figure 3). Nineteen interventions evaluating 6,613 participants were identified across all studies in the United States, and 4,577 women participated.
Nausea and vomiting
Twenty-nine references were included; 25(89.21%) are RCTs and 4(13.73%) are quasi-experiments with participants between 16 and 96 years of age. We reviewed 4(12.91%) care and counseling programs, 5(16.14%) muscle relaxation techniques, 4(12.95%) guided relaxation with music therapy and imagery, 2(6.44%) natural drinks, 2(6.43%) therapeutic touch and reflexology, 12(38.70%) acupressure at P6 point, and 2(6.41%) hologram bracelets. Studies on interventions such as acupressure were consistent in affirming that there was improvement before and after the intervention; however, they showed high heterogeneity regarding the types of interventions and scales used to measure nausea and vomiting (Table 2).
Anorexia
One RCT conducted in Turkey16 involving women aged 29 to 69 years with stage Il or Ill gynecological cancer was included. The intervention involved a nursing program based on Jean Watson's theory. Nursing professionals visited and followed up with the participants via telephone for 60 to 120 minutes once a week. Information on symptom management was provided and compared with standard hospital management. The authors assessed changes in appetite using the Chemotherapy Symptom Assessment Scale (C-SAS). They found that the intervention group had a lower mean change in appetite of 1.00 SD (0.61) than the control group of 2.00 SD (1.08). This study had a high risk of bias due to the lack of randomization and blinding.
Alopecia
Eight studies evaluated non-pharmacological interventions to control alopecia, such as scalp cooling with hypothermic caps, and one study used videos on makeup and wigs. Five studies used WHO criteria to evaluate the effect of scalp cooling on reducing alopecia. The other studies used instruments such as the Dean scale, the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and the breast cancer stem cells (BC SCs) to assess the efficacy of the intervention on hair loss. In general, these studies have a high risk of bias, and scalp cooling shows a possible effect on reducing alopecia compared to placebo (Table 3).
Pain and neuropathy
A total of 1,403 patients, aged 15 to 86 years, were observed in 14 studies. Interventions included educational programs, acupuncture, physical activity, psychological therapies, natural substance applications, massages, and foot baths. Pain and neuropathy were measured using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC), Numerical Pain Scale (NPS), the Dutch Language Version of the McGill Pain Questionnaire (MPQ-DLV), and Symptom Experience Scale. Of the total, 6 (42.81%) studies evaluated disease-related pain, and 8 (57.20%) studies evaluated platinum or taxane chemotherapy-related neuropathy (Table 4). These studies have a high risk of bias due to selective reporting of outcomes, lack of concealment, and lack of blinding. Interventions such as home-based care nursing programs and acupuncture were demonstrated to reduce mean pain and neuropathy when comparing pre- and post-intervention measurements.
Sleep disorders
Nine studies evaluated non-pharmacological interventions to control sleep disorders. Acupressure, telephone follow-up programs, home exercises, relaxation therapies such as foot baths, mindfulness therapies, back massages, and Chinese practices like Chan-Chuang qigong have been studied for their effectiveness in improving sleep quality. However, it is observed that interventions such as acupressure and physical exercise improve sleep quality when comparing intervention groups with post-intervention control groups (Table 5).
Neutropenia
Two studies analyzed 167 participants diagnosed with neutropenia, defined as a decrease in neutrophils following chemotherapy treatment, and administered Chan-Chuang qigong therapy for 21 minutes over 21 days. This technique includes mind and body relaxation, with white blood cell counts measured before and after the procedure. The studies have a high risk of bias due to the nonrandomization of participants, but the intervention showed an increase in white blood cell counts after the intervention (Table 6).
Discussion
This review described non-pharmacological interventions for controlling the primary side effects of chemotherapy with a high degree of heterogeneity and internal validity among the studies. This is consistent with some studies stating that non-pharmacological interventions are complementary to medical treatments; however, they emphasize the lack of valid evidence to present the effect of these interventions as complementary to pharmacological treatments73,74.
The review described several types of non-pharmacological interventions to address the side effects of chemotherapy. These interventions include education and exercise programs, hypothermia devices, acupressure techniques, music therapy, traditional Chinese medicine techniques, relaxation techniques, foot baths, and transcutaneous electrical nerve stimulation75,76.
Nurse-led home-based patient education programs are designed to manage symptoms. These nonpharmacological interventions have shown measurable differences in pain levels before and after the intervention54,59. A need was identified to standardize educational programs and to know the content and indicators for pain assessment26,27,29, However, for patients with multiple symptoms, these processes should be accompanied by psychological support and strengthening of mental health to ensure beneficial application and results in the control of the symptoms.
Holistic medical systems such as acupressure have been studied extensively. This review found that acupressure consistently reduced nausea and vomiting compared to standard care in all measurements30. This result is consistent with the study by Lee A et al.78 who conducted a review and found that acupressure at the P6 point has a moderate effect compared to placebo, although the studies have limitations in terms of variation in effects and methodological quality. However, when comparing acupressure with antiemetics, no difference in the incidence of nausea and vomiting was observed. Therefore, it can be concluded that the available evidence may support a combined therapy of P6 point stimulation and antiemetic drugs rather than drug prophylaxis alone and that further high-quality trials are needed76,79
Manipulative and body-based practices, such as muscle relaxation therapies, reflexology, and therapeutic touch, along with sensory intervention techniques like music therapy and guided imagery, have been described and evaluated with positive effects80,81 however, the reported studies record wide variability of populations, techniques, and study periods regarding outcomes such as pain, nausea and vomiting78,81. The main limitation of these studies was the lack of control for confounding factors, such as the use of medications and other therapies and individual perception of the symptom.
It is important to consider that these types of studies are valuable in building the body of evidence that will later support evidence-based recommendations82. The literature consistently states that acupressure is a complementary technique and does not replace traditional treatment79. The reported studies agree that environmental factors and the use of patients' unreported therapies limit the evaluation of interventions; hence, there is a need to identify what type of interventions patients are conducting.
The immune system's vulnerability to opportunistic infections and the extended duration of treatment make neutropenia a priority in evaluating non-pharmacological interventions. Chan-Chuang qigong therapy has been evaluated in people diagnosed with cancer69,72 and showed an increase in white blood cell count before and after the intervention. However, variables such as time, comorbidities, and treatments must be controlled to estimate the true effect of this intervention.
Alopecia is one of the secondary symptoms that compromise biological, psychological, emotional, and social aspects, affecting the health status of people who suffer from it and is increasingly becoming a priority outcome for the well-being of patients83,84. Video tutorials for makeup, wig styling, and scalp cooling are techniques that have been increasingly reported in recent years to mitigate these effects and improve the quality of life for patients. There is a need to further clarify alopecia measurement strategies with validated scales for different populations.
This review included observational and experimental studies, giving a broad overview of the interventions reviewed. These results suggest some implications for clinical practice and future research. First, each of these interventions and their results should be considered with caution since the representativeness of the populations and the standardization of the techniques used can only be generalized to patients with characteristics similar to those studied in the included studies. Secondly, for research purposes, it is highly recommended that future reviews focus on interventions by symptom clusters". The search strategies used in this review enabled us to capture the broadest selection of relevant literature according to the side effects of chemotherapy using distinct search terms. The included studies showed low methodological quality and evidence that interventions could have a real effect on controlling various symptoms, as evidenced by acupressure on symptoms such as nausea and vomiting, sleep disorders, pain, and neuropathy. The findings of this review highlight the gaps in the available literature and emphasize the importance of further documenting the effect of non-pharmacological interventions on chemotherapy side effects.
Conclusion
Prioritizing side effects for patients guides care plans for individuals. Non-pharmacological interventions such as acupressure, Chinese therapies such as Chan-Chuang qigong, muscle relaxation therapies, and nursing intervention programs have been evaluated and described with evidence for nausea and vomiting, pain and neuropathy, sleep disorders, alopecia, neutropenia, and anorexia. However, there is still high variability in the type of intervention, outcomes measuring, and lack of statistical power, making it difficult to estimate the effects of these interventions. Research with methodological rigor and standardization of these interventions is needed to validate their effects on these outcomes.
Conflict of Interest: The authors declare no conflicts of interest.
Funding: Own funds.
Acknowledgment: We thank Nurse Ana Beatriz Pizarro for her contribution to the selection of the review articles.
How to cite this article:
Gómez-Neva María Elizabeth, Pulido Ramirez Edwin, Ibañez Rodriguez Leidy Johana, Caroprese Oscar, Buitrago-Lopez Adriana. Non-pharmacological interventions for side effects of antineoplastic chemotherapy prioritized by patients: systematic review. Revista Cuidarte. 2024;15(3):e3612. https://doi.org/10.15649/cuidarte.3612
Highlights
* This systematic review represents the standard of evidence used to describe non-pharmacological interventions and alternative therapies to manage antineoplastic chemotherapy's side effects.
* The secondary symptoms of antineoplastic chemotherapy were a priority for patients and caregivers, who identified specific non-pharmacological interventions for each prioritized symptom.
* The need for standardizing interventions and outcome assessment criteria is highlighted, which would facilitate the development of primary studies and their inclusion in systematic reviews.
* The need for studies to evaluate the effect and safety of non-pharmacological interventions for the care of patients diagnosed with cancer is emphasized.
Received: November 29th 2023
Accepted: July 12th 2024
Published: October 11th 2024
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Abstract
Introducción: Diferentes intervenciones no farmacológicas se han estudiado para manejar los síntomas derivados de la quimioterapia, pero se desconoce su efectividad. Objetivo: Describir las intervenciones no farmacológicas para el manejo de síntomas secundarios a la quimioterapia antineoplásicaenadultos. Materiales y Métodos:Revisión sistemática deestudios experimentales y observacionales analíticos (2021 a 2023). La selección de estudios y extracción de datos se realizó de forma paralela. Las discrepancias se resolvieron con un tercer revisor. Se evaluó el riesgo de sesgo con las herramientas Risk Of Bias (RoB) y The Newcastle-Ottawa Scale (NOS). La síntesis de la literatura se realizó de forma descriptiva por desenlace priorizado. Resultados: Los desenlaces priorizados fueron neutropenia, dolor, neuropatía, náuseas, vomito, alopecia, anorexia y desordenes del sueño. Se encontraron 7520 referencias, 62 incluidas para el análisis. La acupresión mostró un posible efecto en el control de síntomas como las náuseas y vomito. La intervención con frio en el cuero cabelludo mostro diferencias en los estadios de la severidad de alopecia. Las otras intervenciones mostraron heterogeneidad. Discusión: Las intervenciones no farmacológicas han sido ampliamente descritas en estudios observaciones y experimentales en el control de efecto secundarios a la quimioterapia, sin embargo, existe homogeneidad, y alto riesgo de sesgo. Conclusión: Acupresión, masaje muscular, musicoterapia, baño de pies entre otros son las intervenciones que se han estudiado para náuseas, vomito, desordenes del sueño, neutropenia, alopecia, anorexia, dolor y neuropatía como síntomas secundarios priorizados por pacientes. Se requiere estandarizar tanto las intervenciones como la forma de medición de los desenlaces.