It is important that patients understand the effects of prescribed medicines, as well as the side-effects and methods of administration, as good medication adherence can lead to more effective treatment, improved safety and continuity of treatment in cancer chemotherapy (1–3). Therefore, it is necessary to investigate medication adherence in patients undergoing chemotherapy with consideration of their understanding of the side-effects.

Multiple studies regarding the adherence of patients to oral anticancer agents have been reported (1,2,4–8). However, thus far, regimen adherence to tegafur/gimeracil/oteracil potassium (S-1) or capecitabine and multiple tyrosine kinase inhibitors have not been examined. Furthermore, the level of awareness of these medicines, which often corresponds to non-adherence by patients, has yet to be investigated. The side-effects of the aforementioned oral anticancer agents are characterized by the development of skin disorders and digestive system side-effects (9–11). In our previous study, a questionnaire survey was conducted to evaluate factors that may affect medication adherence in patients taking oral anticancer agents (3). It was identified that the medication compliance of patients self-administering oral anticancer agents was adequate, however, medication adherence was insufficient. These findings indicate that a patients' interest in their own treatment should be encouraged and interventions should occur according to the condition of the individual patient. However, to the best of our knowledge, no studies have thus far been conducted regarding medication adherence and awareness with regard to the type and therapeutic purpose of individual oral anticancer agents. In particular, as adjuvant chemotherapy is used for the prevention of post-operative recurrence, we propose that medication adherence and awareness is reduced in patients undergoing adjuvant chemotherapy in comparison with those undergoing advanced and recurrent chemotherapeutic regimens.

Therefore, the aim of the present study was to investigate the adherence to medication, and the awareness of oral anticancer agents with regard to the type and therapeutic purpose in outpatients who were self-administering S-1 or capecitabine.

Cancer chemotherapy can be administered as oral single agents, injected single agents, or a combination of oral and injected agents (12–14). Cancer treatment with oral anticancer agents has the advantage of ease of delivery, however, as medication management is the responsibility of the family or patient, medication adherence can be a problem. In the present study, no significant differences were identified in the adherence to oral anticancer agents with regard to type (S-1 versus capecitabine) or therapeutic purpose (adjuvant therapy versus advanced and recurrent therapies). In addition, with regard to the association between medication adherence and age, medication adherence was considered to be insufficient in elderly patients taking S-1. However, no significant adherence differences were identified with regard to age in patients taking capecitabine (Table III). Furthermore, Hasegawa et al (15) and Tsuboi et al (16) reported greater medication adherence in elderly patients compared with young patients. Therefore, it should be considered that medication adherence may be largely dependent on factors other than age.

The dosing timespans for patients taking S-1 or capecitabine did not appear to affect medication adherence in the present study. In a previous study (3), patients with longer courses of treatment (dosing timespan, ∼220 days) demonstrated insufficient medication adherence. By contrast, the dosing timespan for the S-1 or capecitabine survey participants of the present study was markedly shorter, at ∼150 days (3). Tsang et al (17) reported that adherence decreases rapidly ∼6 months after the commencement of treatment. Therefore, the comparatively short dosing timespan in the present study exhibited no effect on medication adherence.

With regard to medication adherence for S-1 and capecitabine monotherapy or combined injection treatment strategies, it was identified that medication adherence in patients taking S-1 was insufficient in monotherapy as opposed to combined therapy. Combined oral and injection chemotherapy was performed at the outpatient treatment center of Ogaki Municipal Hospital, and continual patient guidance by pharmacists and nurses is provided to such patients. By contrast, such guidance is not currently offered by pharmacists for patients undergoing an oral monotherapy regimen at Ogaki Municipal Hospital. Therefore, the present study proposes that patient guidance, or lack thereof, affected the medication adherence of patients taking oral anticancer agents.

For medication awareness in patients taking S-1 (Table V), concern regarding side-effects was more common in adjuvant chemotherapy patients compared with patients undergoing advanced and recurrent therapies. For patients taking capecitabine, such a difference was not apparent. A possible explanation for this result is that the dosing timespan of patients who took S-1 as an adjuvant chemotherapy was shorter compared with advanced and recurrent therapies (105 vs. 207 days), indicating that patients with short dosing times worried more about possible side-effects. Therefore, the present study concludes that worrying about side-effects is affected more by dosing timespan than by therapeutic purpose.

Patients taking capecitabine in adjuvant therapy scored higher on topic number 10 (̔I have actively researched about my medication̓; Table V), indicating that patients undergoing adjuvant therapy examined the medications they were taking more thoroughly compared with those undergoing other types of therapy. For patients receiving combined therapy with capecitabine, the number of patients in the adjuvant chemotherapy or advanced and recurrent chemotherapies groups were as follows: Adjuvant chemotherapy, 7/10 cases; advanced and recurrent chemotherapies, 6/16 cases. Therefore, as previously mentioned, continued patient guidance by pharmacists in outpatient treatment centers may lead patients to take a greater interest in their own medications. In patients receiving S-1 therapy, no guidance was received, as S-1 was predominantly used as a monotherapy. Accordingly, it was identified that S-1 patients did not conduct thorough research of their medication.

With regard to the association between awareness scores for topic number 11 (̔worry about side-effects̓) and age, the correlation was weak; however, the tendency was for younger patients to worry about side-effects more and research the administered medications more thoroughly. By contrast, elderly patients displayed low interest in the prescribed medication and no anxiety regarding the possible side-effects. The low interest in medications by elderly patients may indicate that their ability to manage medication side-effects is lacking. In our previous study (3), patients with insufficient medication adherence did not fully understand the possible side-effects. In cancer chemotherapy, if the patient does not understand the side-effects and the methods to assuage them, then the safety of the patient and the continuity of the treatment strategy is threatened. Therefore, it is important to encourage a patient's interest in their own treatment medication. The results of the present study indicate that continual pharmacist guidance may improve patient management of possible therapeutic side-effects.

In conclusion, the present study identified that for the patients taking S-1 or capecitabine, the type and therapeutic purpose of the oral anticancer agents did not appear to significantly affect medication adherence. However, differences in medication adherence by therapy type (monotherapy versus combined therapy) were identified. In addition, elderly patients expressed low interest in their assigned medications and tended to exhibit insufficient medication adherence. Therefore, we propose that with continued medication guidance, elderly patients taking oral anticancer agents may be more interested in learning about the chemotherapeutic agent they are taking. Thus, patient guidance by pharmacists is important, as it may lead to improved medication adherence and understanding of the possible side-effects.