Keywords
cancer - chemotherapy - drug adherence
Biswajit Dubashi
Background
Adherence to treatment is essential for complete cure. Many oral anticancer regimens
have been approved for treatment with equivalent efficacy to parenteral regimens.
However, the question of adherence arises. Suboptimal adherence is a barrier to effective
use of oral anticancer drugs.[1] Nonadherence also affects the patient–physician relationship and has a negative
effect on the patient’s views about physicians and services.[2]
Oncologists assume that cancer patients will take their medications as prescribed.[3]
[4] Therefore, this study will help us understand the prevalence of nonadherence. Poor
adherence leads to unfavorable outcome and decreases the 5-year event-free survival
of the patients. It will decrease the likelihood of achieving complete cytogenetic
response.[5] Nonadherence also leads to unwanted diagnostic and treatment procedures, causing
health problems.[2]
Aims and Objectives
The primary objectives of the study were to determine the adherence rates of oral
anticancer regimens for different types of cancer in an urban setting and to determine
the various factors affecting adherence.
Materials and Methods
The study is cross-sectional analytical consisting of a single group. All fit patients,
(patients who were able to fill the questionnaire on their own or able to answer the
questions when asked) > 18 years of age, and on oral anticancer drugs for cancer who
have taken the drug for at least 1 month, with or without concomitant intravenous
(IV) anticancer drugs, were included in the study. Convenient sampling was done. All
consecutive patients fulfilling inclusion criteria attending the Medical Oncology
Outpatient Department clinic from June 2017 to September 2017 were taken up for the
study. The basic sociodemographic details about the cancer diagnosis and the treatment
were collected using a pro forma. A standardized Tamil questionnaire consisting of
a set of questions to identify the factors affecting adherence was used. To determine
adherence, the Morisky–Green–Levine (MGL) adherence scale[6] was used.
The Institute Ethics Committee approval was obtained. The questionnaire and the MGL
scale were translated into Tamil and the Tamil form was retranslated to English by
another person and checked for standardization.
Statistical Analysis
The association of adherence with the categorical variable was performed by Chi-square
or Fisher’s exact test. The independent factors associated with adherence pattern
were explored using logistic regression analysis. All statistical analysis was performed
by 5% level of significance, and p < 0.05 was considered as statistically significant. The analysis was performed by
SPSS version 19.
Observation and Results
The study included 152 patients fulfilling the inclusion criteria. It was found that
73% of the patients were adherent and 27% of the patients were nonadherent. The mean
age of the study population was 49.03 ± 13.4 years. Approximately 52.6% of the patients
were > 50 years of age, with equal proportions of males and females, and 93.4% of
the patients had a caretaker. About 30% of the patients were uneducated and 45% of
the patients were unemployed. Nearly 54.6% of patients were on treatment for < 12
months’ duration (median of 9 months with an interquartile range of 4–42 months) and
34.2% of patients did not take any oral supportive medications. About 71.7% of the
patients took their medications themselves and 41.4% of patients experienced adverse
drug reactions (ADRs). About 63.7% of patients had solid malignancies and the rest
were hematological malignancies ([Table 1]).
Table 1
Distribution of study participants based on type and stage of cancer and details of
oral anticancer medications intake (n = 152)
|
Details
|
Study population (n = 152)
|
|
Abbreviations: 6MP, 6-mercaptopurine; ADR, adverse drug reactions; ALL, acute lymphoblastic
leukemia; CLL, chronic lymphoid leukemia; CML, chronic myeloid leukemia; MTx, methotrexate;
NHL, nonHodgkin lymphoma.
|
|
Hematological malignancies
|
56 (36.8)
|
|
ALL
|
6 (3.9)
|
|
CLL
|
2 (1.3)
|
|
CML
|
47 (30.9)
|
|
NHL
|
1 (0.66)
|
|
Solid malignancies
|
96 (63.2)
|
|
Breast carcinoma
|
25 (16.4)
|
|
Stomach carcinoma
|
23 (15.1)
|
|
Colorectal carcinoma
|
25 (16.4)
|
|
Others
|
23 (13.3)
|
|
Stage of cancer
|
|
Early
|
58 (38.1)
|
|
Locally advanced/metastatic
|
92 (60.5)
|
|
Unknown
|
2 (1.3)
|
|
Oral anticancer medication
|
|
Capecitabine
|
55 (36.2)
|
|
Imatinib
|
51 (33.5)
|
|
Letrozole
|
14 (9.2)
|
|
Tamoxifen
|
10 (6.6)
|
|
Gefitinib
|
7 (4.6)
|
|
6MP, MTx
|
6 (4)
|
|
Hydroxyurea
|
3 (2)
|
|
Sorafenib
|
2 (1.3)
|
|
Chlorambucil
|
2 (1.3)
|
|
Nilotinib
|
1 (0.7)
|
|
Prednisolone
|
1 (0.7)
|
|
Number of tablets/day
|
|
1–3
|
67 (44.1)
|
|
4–6
|
38 (25)
|
|
5–8
|
36 (23.7)
|
|
Unknown
|
11 (7.2)
|
|
Frequency of administration (daily)
|
|
Once
|
92 (60.5)
|
|
Twice
|
58 (38.2)
|
|
Thrice
|
2 (1.3)
|
|
Duration of oral anticancer drug intake in a month (days)
|
|
5–14
|
3 (2)
|
|
15–21
|
27 (17.8)
|
|
22–30
|
122 (80.2)
|
|
Coadministration with intravenous anticancer drugs
|
|
Yes
|
54 (35.5)
|
|
No
|
98 (64.5)
|
|
Withholding of drugs by doctor
|
|
No
|
116 (76.3)
|
|
Yes
|
36 (23.7)
|
|
Reasons
|
|
Low counts
|
11 (30.5)
|
|
ADR
|
5 (13.9)
|
|
Fever
|
3 (8.3)
|
|
Others
|
19 (52.8)
|
|
ADR
|
|
No
|
89 (58.6)
|
|
Yes
|
63 (41.4)
|
About 97.4% were aware that they had cancer, and 12.5% of patients were aware of the
diagnosis, treatment, and outcome. About 61.2% received majority of the information
before treatment initiation, 93.4% of the patients received majority of knowledge
from physicians, and 42.8% of the patients were aware about the outcomes of nonadherence.
Only 9.2% of patients stopped drugs intermittently without consulting the physicians.
Almost 98% did not use any methods to avoid forgetting to take medications. About
23% of patients experienced difficulty in remembering to take medications on time,
and 11.8% of patients considered taking medications as an inconvenience. A major proportion
of patients (67.1%) visited their physicians once in every 3 to 4 weeks. Only 16.5%
of patients visited doctors besides scheduled visits, with the most common reason
being pain due to illness, followed by side effects, fever, and doubts regarding drug
intake in decreasing order of magnitude. About 92.8% of patients were satisfied with
their physicians.
Adherence rates in gastric cancer and breast cancer were 60% and 68%, respectively.
Chronic myeloid leukemia (CML) and colorectal cancer had a better drug adherence rate
of 75%. A majority of the patients (75.6%) who were nonadherent mentioned forgetfulness
as a reason for being nonadherent followed by carelessness ([Table 2]).
Table 2
Reasons for nonadherence (n = 41)
|
Reason
|
Study population
|
|
Forgetfulness
|
31 (75.6)
|
|
Carelessness
|
9 (21.9)
|
|
Not taking drugs when feeling better
|
3 (7.4)
|
|
Not taking drugs thinking they are harmful to the body
|
5 (12.1)
|
|
More than one reason was mentioned by patients as reasons for nonadherence
|
On bivariate and multivariate analysis, we observed that patients with < 1 year of
treatment, adverse effects, taking oral anticancer drugs for < 21 days per month,
coadministered with IV anticancer drugs, and patients with more than once daily dosing
had significantly poor adherence. Bivariate analysis of other variables such as age,
sex, caretaker, occupation, income, hospital distance, comorbidities, type and stage
of cancer, chemotherapy regimen, dose of drugs, oral supportive drugs, knowledge about
disease, and treatment were insignificant. On multivariate analysis, only ADR showed
a trend toward correlation with nonadherence.
Discussion
In spite of increased use of oral anticancer drugs in the recent times, the number
of studies addressing the issue of adherence is very low. The study assessed the adherence
of oral anticancer medication in a tertiary cancer government hospital. We identified
that 27% were nonadherent. Our study looked at adherence rates both in solid and hematological
tumors. In a study by daCosta et al, which was done to assess the patient preferences
and treatment adherence among, 34.8% of the women diagnosed with metastatic breast
cancer were nonadherent. Patients receiving hormonal therapy reported the highest
level of nonadherence.[6] Forgetfulness was higher in our population when compared with a study in noncancer
patients.[7] In our study, 75.4% of CML patients on imatinib or hydroxyurea were adherent when
compared with the study by Marin et al, which reported median adherence measured by
microelectromechanical systems (MEMS) was 97.6%.[8] Another study done on adherence among CML concluded that 32.7% of participants were
highly adherent, medium adherence in 46.5%, and low adherence in 20.7% of the study
population.[9] The possible reasons for increased nonadherence rate need to be examined in further
studies. The adherence rate in CML patients as determined by the questionnaire was
74.5% which is correlating with the study done by Noens et al in which they found
questionnaire-based adherence to be between 67% and 97%.[10]
In our study, the presence or absence of a caretaker was insignificant in bivariate
analysis, but a systematic review done to determine adherence to oral anticancer drugs
found out that patients who were living alone had poor adherence. The study also concluded
that lower educational status and patients with no family history of cancer had poor
adherence.[11]
In a study by Timmers et al, the adherence rate in patients on anticancer drugs experiencing
ADR was 33%, which was low when compared with our study.[12] Veronesi et al[13] and Demissie et al[14] reported a nonadherence rate of 26.7% and 15%, respectively, to hormonal therapy
in breast cancer, which was lower than our study (32%).
Conclusion
Drug adherence is one of the key factors for treatment failure in cancer patients.
ADRs have been found as an independent variable, resulting in decreased drug adherence.
Duration of treatment, coadministration with IV chemotherapeutic drugs, duration of
oral anticancer drug intake in a month, and frequency of drug intake (anticancer drug)
were significant factors which affect oral anticancer drug adherence. Understanding
and identification of early adverse events and interventions will help decrease treatment
failure. Knowledge about the disease, understanding the drug prescription, and side
effects were lacking in our study group.
