Recent progress in treatment of cancer has accelerated an expansion of the development of oral anticancer agents [1]. The availability of oral anticancer agents has a major impact on cancer care. In oral chemotherapy, some of the traditional responsibilities of healthcare providers have shifted to patients [2]. Despite increased patient’s responsibility for self-management, oral therapy is preferred by patients mainly because of no need for clinic visits, no needle placement, and reduced cost [3–5].

As a growing number of patients are choosing oral chemotherapy over intravenous administration [6], the issue of adherence is becoming increasingly important in oncology [7–9]. Traditionally, adherence was not a major problem in cancer patients compared to other chronic disease [10] because cancer treatment were usually provided in acute care settings, and intravenous chemotherapy has been strictly controlled at outpatient clinic by healthcare providers. The convenience of oral medication has a flip side—serious complications and fatal outcomes. Oral chemotherapy is cost effective, if it is taken as prescribed [11]. However, if patients are non-adherent to medication, the cost burden of unused medicines is substantial.

The terms “adherence” and “compliance” are used interchaneably, but “adherence” is generally preferred to “compliance” because “compliance” suggests that patient is a passive follower of the doctor’s orders, and “adherence” implies that the treatment plan is based on a therapeutic alliance between the patient and the healthcare provider [12]. Optimal adherence is achieved “if no doses are missed, no extra doses are taken, and no doses are taken in the wrong quantity or at the wrong time” [10]. In general, a patient is considered to be adherent if he or she has taken 80% of a prescribed medication [1].

A number of factors are interrelated with medication adherence. There are three levels of barriers to adherence: patient, healthcare provider, and healthcare system levels [12]. The patient-level factors include health beliefs and socioeconomic factors, while communication and the complexity of the regimen are regarded as healthcare-provider factors [8]. Healthcare system issues include duration of treatment follow-up visits, prescribing errors, and conflicting information regarding the consequences of non-adherence [3].

To overcome barriers to patient adherence, there is no single standard intervention [13]. However, multidisciplinary and multimodal strategies are considered as effective [1]. Also, the literature places a primary emphasis on patient education [4, 8, 14, 15]. Education should be tailored for individual patients, and patients generally prefer direct interaction with healthcare providers [4]. Other suggested interventions include systematic monitoring of patient pill taking, and use of pill diaries and pill counting [10].

The primary roles of oncology nurses in patients on oral chemotherapy include patient education, communication, symptom management, and proactive follow-up [16]. Their skills help patients with side-effect management and handling medications at home, and patient adherence to medication can be improved by follow-up care [5]. The ASCO/ONS chemotherapy administration safety standards including oral agents have been established in 2013 [7]. A national web-based survey on current nursing practice patterns for oral chemotherapy in the United States reported that only half of the nurses worked in practices with specific policies, procedures, and resources for patients on oral chemotherapy, and found erratic procedures and inadequate interdisciplinary communication in many practices [17]. Additional research is needed to determine the best practice in patient education, monitoring, and safety management, and furthermore, to identify the gaps that may exist between the nurses’ roles and practice [16, 17].

We conducted a multicenter cross-sectional questionnaire survey in designated cancer centers and at large general hospitals in Japan. The goal was to determine a baseline of nursing practices for oral chemotherapy in order to improve medication adherence.

Of the 450 hospitals providing ambulatory chemotherapy, 388 declined to participate in the study. Reasons for non-participation included refusal or non-response of person in charge (the nursing director forwarded the questionnaire to the nurse in the chemotherapy clinic but did not receive a reply) (n = 257), lack of time or staffing (n = 58), prior participation in other surveys (n = 83), practical difficulties (n = 40), and other (n = 66). A total of 62 hospitals consented, and 62 nurses in those hospitals participated in the survey. Of 930 patients who were systematically sampled, 249 had received oral chemotherapy. Therefore, 62 nurses fulfilled the patient-based survey about these 249 patients who those nurses cared for.

This is the first report on current nursing practices for patients receiving oral chemotherapy in Japan. There was great variation in practices across the nation. The survey results demonstrated that a majority of the cancer centers and large hospitals in Japan are responding to the emerging needs of oral chemotherapy in conventional care systems, with only a minority incorporating systems specific to oral chemotherapy. Adherence-related nursing practices were associated with the nurse’s background, the type of treatment, and healthcare system-related factors.

First, nurses should be aware of their role in monitoring the medication management of patients receiving oral chemotherapy. In the present study, nearly 20% of nurses were not aware of their monitoring role. Although nurses educate patients about intravenous chemotherapy, few are involved in oral chemotherapy [5]. As understanding the clinical importance of oral chemotherapy is reported to encourage adherence in 90% of patients [3], patient should be made well aware of both the benefits of medication and the risks of non-adherence [14]. Patient education is the cornerstone of successful oral chemotherapy [8, 15]. A feasibility pilot study of new medication adherence interventions suggests that nurses have an important role to play in education, monitoring, and follow-up [21]. A strong patient-nurse relationship is fundamental to individualized education, leading to successful management of and adherence to treatment regimens [4].

The nurses were unlikely to ask how patients understood the therapy and how they managed medication at home, and very few nurses asked whether patients were confident in medication management. Patients may not be confident in medication management, but nurses do not know how they feel about isolation. At least, nurses should ask patients whether they are taking their medication as prescribed. Information the nurse could gain from this simple question is worth to ask. The answer implies patient adherence to medication. Recently, nurses’ contact with patients is decreasing [18]. It is because oral chemotherapy is often administered outside of controlled settings [7], and patients usually receive medication information directly from the oncologist or pharmacist without nursing support [16]. Regular contact with a single nurse helps promote patients’ trust [22], and facilitates identification of concerns about treatment and daily life activities. The patient-nurse relationship and collaboration of the healthcare team are essential components of patient adherence [23]. A proactive attitude on the part of the nurse is a key in caring for patients on oral chemotherapy.

Healthcare-system related factors were predictors of adherence-related nursing practices in this study. Such factors included patient orientation with an overview of oral chemotherapy presented by a nurse, interdisciplinary learning opportunities, and a system-based approach for detecting prescription errors. As oral chemotherapy becomes more common, more patients will require education. Patient orientation for oral chemotherapy should be systematically implemented for every patient who initiates this type of therapy. Patient education about the disease, treatment, and symptom management is the role of the oncology nurse [24], and staffing for orientation is important to ensure patients receive the necessary education.

Currently, healthcare providers have little ability to directly manage oral chemotherapy care [25]. There is great value in creating an efficient and effective interdisciplinary team among healthcare providers in cancer care [26]. Interdisciplinary learning opportunities remind team members of their roles, integrate professional knowledge, and facilitate collective work [27].

Regarding prescription errors, intravenous chemotherapy is commonly double-checked or triple-checked by multiple staff in controlled settings. The safety issues in oral chemotherapy are just important as those in intravenous chemotherapy [2], however, the safe delivery of oral chemotherapy may depend on the competency of those dispensing the medication [7]. Including a set routine in an organization’s safety infrastructure can raise the awareness of healthcare providers on safety and monitoring of administration of oral anticancer agents. Institutional safety infrastructure is critical for favourable clinical outcomes [15].

In the present study, nurses asked about adherence to medication regimens more frequently when patients were on oral chemotherapy alone, rather than on combined intravenous and oral chemotherapy. This may have been in part because nurses must focus on strict standards in administering intravenous chemotherapy, and therefore might not have the time to ask about oral medication. Adherence is not only an issue for patients new to oral chemotherapy, but also for those with refilled prescriptions [28]. As shown in the results of the present study, nurses are less likely to monitor medications of patients with refilled prescriptions. Cancer patients tend to undergo long-term treatment, and therefore the concept of follow-up, keeping track of the condition of cancer patients, is important. Shared accountability among multiple providers in cancer care makes individual accountability blur. In addition to individual commitment to care, major improvement requires coherent strategies of the organization.

There are a number of limitations to the present study. Systematic sampling is vulnerable to periodicities which might lead to bias. Very few hospitals approved the survey because of strict regulations on patient data. We confirmed that all hospitals received invitations to participate in the survey, but could not reach the person in charge at all the hospitals we approached. Thus, low response rate may have produced a bias if the replies from respondents were not representative of the national sample. The present study relied on the nurses’ response to the questionnaires. We did not measure actual patient adherence to medication regimens. This survey focused on chemotherapy clinics; outpatient and primary care settings were not included. Therefore, the results of the survey do not reflect the overall picture of oral chemotherapy treatment. The results of the logistic regression suggested that nurses with higher education were unlikely to ask about unused medicines, which is difficult to explain; however, there were only 6 nurses who had educational backgrounds higher than university. This small number might have produced the unexpected result.

A multicenter cross-sectional survey revealed that adherence-related nursing practices were associated with the nurse’s background, type of treatment, and healthcare system-related factors, including patient orientation on oral chemotherapy, interdisciplinary learning, and having a system-based approach for detecting prescription errors. With the increase of oral chemotherapy, a new model of patient care is required. A more systematic approach should be developed to ensure patients receive safe and effective oral chemotherapy, while nurses should play significant roles in patient education and monitoring.

Further studies are needed to develop an organized system of care in which nurses proactively support patients in managing safe and effective oral chemotherapy and improve medication adherence with coordination among healthcare providers.