Effects of auricular acupressure on chemotherapy-induced nausea and vomiting in breast cancer patients : a preliminary randomized controlled trial

Abstract

Background Chemotherapy-induced nausea and vomiting (CINV) is regarded as one of the most upsetting and frequently seen adverse reactions during antineoplastic therapies. Given the fact that using antiemetic medications alone cannot completely manage CINV, different non-pharmacological treatments have therefore been utilized in research and practice to be used in combination with conventional antiemetics to deal with nausea and vomiting during cancer chemotherapy. Among these treatments, auricular therapy (AT) is a promising candidate but relevant research evidence is scarce at present. Aim and objectives The aim of this study was to evaluate the feasibility of an evidence-based AT treatment protocol for CINV management in female breast cancer patients receiving chemotherapy and preliminarily examine the effects of AT on CINV and quality of life (QoL) via a pilot randomized controlled trial (RCT). The study objectives were: (1) to develop an evidence-based AT treatment protocol for CINV management; (2) to pilot the methodological procedures of the RCT; (3) to determine the eligibility rate, recruitment rate, retention rate, and attrition rate during the pilot RCT subject recruitment and follow-up process; (4) to determine the feasibility and acceptability of the study questionnaires and the AT treatment protocol administered to the participants; (5) to identify potential adverse events associated with AT; (6) to preliminarily examine the effects of AT on CINV and QoL; (7) to explore the participants' experiences of participating in the pilot RCT and receiving the AT treatment; and (8) to refine the study protocol for a future multicenter large-scale RCT to examine the definite effects of AT on CINV and QoL in female breast cancer patients. Methods The Medical Research Council (MRC) Framework for Developing and Evaluating Complex Interventions was employed to guide the research design. An evidence-based AT treatment protocol was developed first based on several recent systematic reviews, relevant AT theories and handbooks, the Chinese standard ear acupoint chart, and characteristics of the CINV symptoms. The AT treatment protocol was then evaluated by a group of experts to determine its content validity. A pilot RCT was utilized afterward. A total of 114 female breast cancer patients scheduled to be treated with the first cycle of chemotherapy were recruited from three medical centers in Fuzhou and were randomly assigned to the true AT group, the sham AT group, or the standard care group. The participants in the true AT group received a five-day true AT plus standard antiemetic treatment and care, the participants in the sham AT group received a five-day sham AT plus standard antiemetic treatment and care, and the participants in the standard care group received standard antiemetic treatment and care only. The MASCC Antiemesis Tool (MAT) was employed to measure CINV. The Functional Assessment of Cancer Therapy-Breast (FACT-B) was utilized to measure QoL. The likelihood of causality between AT and the reported adverse events was assessed using the WHO-Uppsala Monitoring Centre (UMC) System for Standardized Case Causality Assessment. In addition, anticipatory CINV was also evaluated using the Index of Nausea, Vomiting, and Retching (INVR). After completing the RCT, semi-structured interviews were conducted to explore the participants' experiences of participating in the pilot trial and receiving the AT treatment. Results A total of 114 patients were recruited to participate in the pilot RCT and 110 of them completed the outcome assessment (completion rate: 96.5%). Acceptability of the study questionnaires was adequate, with missing values identified in only a few FACT-B questionnaire items. The AT treatment protocol was found to be feasible for use, as the majority of participants (80.3%) from the true AT group and the sham AT group followed the study protocol to complete the five-day AT treatment. Adverse events associated with AT, such as minor pain and discomfort, were identified by a few participants but the reactions were generally mild, tolerable, and transient. The participants in the true AT group and the sham AT group had higher complete response (CR) rates of CINV symptoms than those in the standard care group, with the among-group difference in the CR of acute CINV reaching statistical significance (p=0.03). The occurrence and severity of acute CINV in the true AT group were lower than in the sham AT group, and both the true AT group and the sham AT group reported a lower occurrence and severity of acute CINV than that of the standard care group. Statistically significant among-group differences were identified for the occurrence of acute nausea (p=0.04) and the severity of acute nausea (p=0.001). Delayed CINV was also lower in the true AT group and the sham AT group than in the standard care group, but no statistically significant differences were found among the groups. The MAT total and domain scores in the true AT group and the sham AT group were all lower than those in the standard care group. Statistically significant differences in the MAT overall total (p=0.004), MAT total nausea (p=0.003), MAT acute CINV (p=0.002), and MAT acute nausea (p=0.001) scores were found among the groups. There were no statistically significant differences in anticipatory CINV and QoL among the groups at post-intervention (follow-up) assessment. Twenty-seven participants took part in the semi-structured interviews. The interviewees generally viewed that complementary healthcare approaches (CHAs) could be used as convenient and safe adjuvant approaches to conventional medicine. The majority of the interviewees felt that the study questionnaires were easy to understand and the MAT questionnaire accurately recorded their CINV symptoms. Most of the interviewees from the true AT group and the sham AT group strictly followed the study protocol to complete the five-day AT treatment, and the majority of the interviewees viewed AT as a safe and convenient approach. Most of the interviewees from the true AT group and the sham AT group perceived that AT produced some beneficial effects in relieving their CINV symptoms, while a few of them believed that AT did not have specific treatment effects for CINV but did provide some "psychological comfort". Conclusion The evidence-based AT treatment protocol demonstrated that it is a safe, feasible, and convenient non-pharmacological intervention for use among female breast cancer patients. The use of AT plus standard antiemetic medication and care showed superiority over the use of standard antiemetic medication and care alone in managing acute and delayed CINV, and the antiemetic effects of AT were found to be more profound in alleviating acute CINV symptoms, particularly acute nausea. However, it should be noted that the antiemetic effects of AT were a mixture of specific treatment (true) effects and non-specific treatment (placebo) effects. The preliminary research evidence from this study supports the hypothesis that AT is a safe, convenient, and promising non-pharmacological intervention for alleviating CINV in breast cancer patients undergoing chemotherapy, and future practice is encouraged to utilize AT as a promising complementary treatment approach to assisting CINV management in cancer patients. A future multicenter large-scale RCT is needed to examine the definite effects of AT on CINV and QoL in cancer patients receiving chemotherapy.