Just a bit outside: An attempt to improve overlooked symptoms and how this may be accomplished

Chemotherapy is a critical element in the management of cancer. Chemotherapy-induced nausea and vomiting (CINV), perhaps the most common and feared side effect of treatment, has significant ramifications for those it affects. Not only does it directly impact the quality of life (QoL), CINV compromises nutritional and hydration status, necessitates treatment modifications, and negatively impacts compliance.^1,2 Patients with malignant glioma (MG) are at heightened risk of nausea and vomiting as tumor location, mass effect and concurrent use of radiation may exacerbate CINV. Furthermore, the QoL of patients with MG, whose survival is measured in months, is a critical consideration. In the setting of poor expected outcomes, treatment toxicity must be balanced against realistic expectations.

Affronti and colleagues explored if the addition of rolapitant on day 1 to daily ondansetron (sequence B) would provide better control of patient-reported nausea and vomiting compared to ondansetron alone (sequence A) during the first 2 weeks of standard therapy.³ The authors utilized a validated patient-reported assessment tool. The timeframe of 2 weeks was chosen because if symptoms are not controlled early on, the treatment may be modified or discontinued. Investigators controlled for patient characteristics that may increase the risk of CINV. Ultimately the study was terminated prematurely because of loss of funding, compromising accrual. Almost 1 in 5 patients did not complete the assessments further limiting conclusions. Despite this there were trends in favor of the combined treatment arm, (74% vs 57% for the primary endpoint and 20% vs 0% for vomiting). In addition, consistent with the rolapitant pharmacokinetic profile, time to first emesis was significantly delayed in patients receiving combined therapy. The authors suggest repeat dosing of rolapitant may have improved efficacy. The authors noted, regardless of the treatment arm, that the incidence of nausea remained high.

Despite recent work demonstrating the need for improvements in supportive care, there remains a dearth of new recommendations and therapies within this focus of medicine for patients with MG.^4,5 This study was an attempt to approach a topic often overlooked and underfunded: supportive care in MG patients. Supportive care is overshadowed by therapeutic research and important topics remain neglected which could have a profound impact on patient outcomes. There is increasing attention focused on QoL research, but barriers to success such as limited funding, subjective nature of the outcomes, utilization of standardized tools, and completeness of data collection create challenges. All these points are exemplified by the reported research. Because of underpowered nature of the study, Affronti and colleagues noted that this trial was “inconclusive” rather than negative, but if this study reached its intended accrual and the data successfully collected, the trends may have reached statistical significance.

Allied Health Providers (AHPs) consist of a large workforce of clinical providers from a variety of disciplines focused primarily on care delivery. Although historically limited, AHPs engagement in research is actively being promoted by professional societies including the Society of Neuro-Oncology. In partnership with other supportive care services, it is within the scope of practice for AHPs to lead processes of care and outcomes research initiatives.^6,7 In collaboration with traditional research infrastructure, AHPs represent an invaluable group to investigate a multitude of poorly understood non-therapeutic topics that nonetheless profoundly impact patient outcomes. The manuscript by Affronti and colleagues exemplifies this. Efforts to enhance such efforts are critical, including developing a supportive infrastructure that educates, promotes, and supports interested individuals.

AHPs, including pharmacists, play a critical role in patient education, not only about their diagnosis but also treatment options, side effects profiles, and the impact on QoL. Medication adherence to not only chemotherapy but also supportive care interventions, such as antiemetics, should be a talking point at every visit to lessen or prevent CINV. AHPs can also ensure guideline adherence with supportive care management, which the investigators excelled at. The authors utilized nurse visits to successfully collect missing data. Similarly, telehealth visits with AHPs allow for opportunities to improve information and address pre-existing notions and fears common among patients that serve as a barrier to effective treatment. Inconsistent compliance by providers with existing evidence-based guidelines has culminated in higher rates of CINV that can be improved through patient education.⁸ In addition, AHPs and pharmacists are in the unique position to evaluate clinical and pharmacogenomic factors that may predict higher toxicity risk. The authors went to great lengths to control for such factors in this study, yet this is not always the case in clinical practice.

Although this study did not have statistically significant outcomes, we agree with the investigators that the results should be characterized as inconclusive due to small accrual and abrupt discontinuation of the trial. There does appear to be a benefit with the addition of rolapitant for control of CINV although the differences were not significant. This study also exemplified the role AHPs and pharmacists can play in research and patient education as it pertains to MG, treatment options and impacts on QoL, as well as the importance of guideline adherence for providers and patients. More work should be undertaken by AHPs to improve the QoL for MG patients.

Funding

The authors received no funding supporting this editorial.

Conflict of interest statement. The authors of this editorial declare no conflict of interest.