Keywords
Cancer - chemotherapy - prescribing patterns - World Health Organization
Introduction
Cancer is a group of disease, involving uncontrolled multiplication and spreading
of abnormal forms of one's own body cells.[1] Mainly, there are two approaches for cancer treatment: local treatment approaches
that include surgery and radiation and systemic treatment approaches that include
chemotherapy and biological agents.[2]
Chemotherapy is a treatment option for majority of cancers. In chemotherapy, drugs
are used to destroy cancer cells. There are different types of chemotherapy that includes
adjuvant chemotherapy, neoadjuvant chemotherapy, induction chemotherapy, consolidation
therapy, maintenance therapy, and palliative chemotherapy. In olden days, cancers
were treated with single drug; but, nowadays, combination of drugs are given to overcome
the cancer cell heterogeneity and development of drug-resistant cells to kill total
tumor cells.[1]
The chemotherapy-induced adverse effects may be uncomfortable; temporary or life-threatening
adverse effects lead to reduction of doses of anticancer drugs, addition of supportive
care drugs. Cancer supportive care involves the management of signs and symptoms or
the management of chemotherapy-induced adverse effects.[3] This necessitates careful observation and evaluation of cancer chemotherapy, which
in turn will help to optimize anticancer therapy with minimal toxicity and improved
efficacy.
Prescribing pattern is an important tool in ascertaining the role of drugs. Prescription
pattern is a process of analyzing the usage of drugs prescribed. Therefore, evaluating
and monitoring the prescription patterns of anticancer drugs and supportive care drugs
are necessary. The World Health Organization (WHO) developed core prescribing indicators
which are meant to measure the characteristics related to polypharmacy, antibiotic
use, drugs prescribed from WHO model list of essential medicines, and the National
List Essential Medicine (NLEM).[4]
Methods
Study design and setting
A prospective observational study was conducted for 8 months from September 2017 to
April 2018 in the Department of Medical Oncology at Justice K. S. Hegde Charitable
Hospital, Mangaluru. Before the initiation of the study, ethical approval was obtained
from the Institutional Ethics Committee (Ref. No: NGSMIPS/IEC/10/2017-18), Mangaluru.
Sample size
The sample size was calculated based on the previously conducted study.[5] The minimum sample size required for conducting the study was 200.
Study criteria
Cancer patients of either gender with age more than 18 years on chemotherapy along
with supportive care medications were enrolled during the study period. Patients undergoing
concurrent radiotherapy and not willing to participate in the study were excluded.
Data collection
All the necessary details for the study were collected from the patient's medical
record at inpatient department, and the medical records were reviewed on daily basis.
All the enrolled patients were followed up to four cycles of chemotherapy. The information
such as age, gender, past medical history, presence of comorbidities, type of cancer,
stage of cancer, social habits, concurrent medications, and drug therapy was convened
systematically and archived in the data collection form. All the drugs were classified
as per the Anatomical Therapeutic Chemical classification (ATC code-level 1, WHO,
2016).[6] All the diseases were classified according to the International Statistical Classification
of Diseases and related health problems (ICD 10, WHO, 2016).[7] In the present study, the WHO core drug prescribing indicators were used to determine
the percentage of antibiotics and injectable prescribed, percentage of drugs prescribed
from NLEM 2015, WHO model list of essential medicines (March 2017), and polypharmacy.[8],[9],[10]
Data analysis
Prescribing patterns of chemotherapy were analyzed by collecting the details of drug
usage including drug name, dose, indication, dosage form, frequency, duration, route
of administration, chemotherapy cycles, and chemotherapy regimens and were recorded
in the data collection form. Similarly, prescribing pattern of supportive drugs used
along with cancer chemotherapy was also recorded from the drug treatment chart and
convened in the data collection form.
Assessment of World Health Organization core drug prescribing indicators[8]
The following formulae were used for the assessment of the WHO core drug prescribing
indicators:
The average number of cytotoxic drugs prescribed = Total number of cytotoxic drugs
prescribed/total number of patients.
The average number of drugs prescribed = Total number of drugs prescribed/total number
of patients.
Percentage of drugs prescribed by generic name = (Number of drugs prescribed by generic
name/total number of drugs prescribed) × 100.
Percentage of encounters with injection prescribed = (Number of patients prescribed
with injection/total number of patients) × 100.
Percentage of encounters with a cytotoxic injection prescribed = (Number of patients
prescribed with a cytotoxic injections/total number of patients) × 100.
Percentage of encounters with antibiotic prescribed = (Number of patients prescribed
with antibiotic/total number of patients) × 100.
Percentage of drugs prescribed from NLEM = (Number of drugs prescribed from NLEM/total
number of drugs prescribed) × 100.
Percentage of drugs prescribed from WHO model list of essential medicines = (Number
of drugs prescribed from WHO model list/total number of drugs prescribed) × 100.
Results
A total of 230 patients with various types of cancer were enrolled in the study. Out
of which, all the patients underwent four cycles of chemotherapy without any dropouts.
In the agewise distribution, majority of patients were in 45–60 years (47%) compared
to the other age groups. The mean age of the study population was 52.17 ± 13.15 years.
In genderwise distribution, majority of the patients were females (51.7%) when compared
to males. Out of 230 patients, 75 patients had social habits, of which, majority of
them were smokers (12.1%) followed by alcoholic patients (11.7%). Majority of the
cancer patients was diagnosed with Stage III (51.3%), followed by Stage II (26.5%).
There are different types of cancer which are commonly classified into solid and hematological
tumors. Out of the solid tumors, breast cancer (21.7%) was most commonly observed
followed by esophagus (10%). Among the hematological tumors, the most commonly observed
cancer was non-Hodgkin's lymphoma (5.7%) followed by multiple myeloma (2.6%). Doublet
regimen (60.4%) was the most commonly prescribed chemotherapy followed by single regimen
(19.1%). The demographic details of the study population are summarized in [Table 1]. Of 44 different cancer types, 36% of patients received doxorubicin and cyclophosphamide
who had carcinoma of breast while paclitaxel and carboplatin (16.52%) were highly
prescribed. The most commonly prescribed chemotherapy regimens among different cancer
types are described in [Table 2].
Table 1
Demographics of the study population
|
Demographic details
|
Number of patients (%), (n=230)
|
|
Others* – Testis, Peritoneal, Supraglottis, Pyriform fossa, Ewing’s sarcoma, Bone
metastasis, Pancreas, DLBCL, Hypopharynx, Gallbladder, Nasopharynx, Spindle cell,
Oropharynx, Cervix, Salivary gland, Chondrosarcoma, PNET of kidney, Synovial sarcoma,
Prostate, Auditory canal, Penis, Periampullary, and Vulva. NHL – Non-Hodgkin’s lymphoma;
HL – Hodgkin’s lymphoma; AML – Acute myeloid leukemia; DLBCL – Diffuse large B-cell
lymphoma; PNET – Primitive neuroectodermal tumors; CKD – Chronic kidney disease; chronic
lung diseases; CLD – Chronic lung diseases; IHD – Ischemic heart disease
|
|
Gender
|
|
Male
|
111 (48.3)
|
|
Female
|
119 (51.7)
|
|
Age groups
|
|
<30
|
15 (6.5)
|
|
30-45
|
45 (19.6)
|
|
45-60
|
108 (47)
|
|
60-75
|
56 (24.3)
|
|
>75
|
6 (2.6)
|
|
Comorbidities
|
|
Hypertension
|
35 (15.2)
|
|
Diabetes mellitus
|
22 (9.6)
|
|
Asthma
|
13 (5.7)
|
|
CLD
|
2 (0.9)
|
|
IHD
|
4 (1.7)
|
|
CKD
|
1 (0.4)
|
|
No comorbidities
|
153 (66.5)
|
|
Social habits
|
|
Smoking
|
28 (12.1)
|
|
Alcohol
|
27 (11.7)
|
|
Substance abuse
|
5 (2.1)
|
|
Both alcoholic and smoker
|
12 (5.2)
|
|
Alcoholic, smoker, and substance use
|
3 (1.3)
|
|
No social habits
|
155 (67.3)
|
|
Cancer stages
|
|
Stage I
|
9(3.9)
|
|
Stage II
|
61 (26.5)
|
|
Stage III
|
118 (51.3)
|
|
Stage IV
|
42 (18.3)
|
|
Solid malignancy
|
|
Breast
|
50 (21.7)
|
|
Esophagus
|
23 (10)
|
|
Lung
|
17 (7.4)
|
|
Ovary
|
15 (6.5)
|
|
Buccal mucosa
|
10 (4.3)
|
|
Stomach
|
9(3.9)
|
|
Colon
|
8 (3.5)
|
|
Rectum
|
7 (3.0)
|
|
Liver
|
5 (2.1)
|
|
Brain
|
4 (1.7)
|
|
Tongue
|
3 (1.3)
|
|
Leiomyosarcoma
|
3 (1.3)
|
|
Urothelial
|
3 (1.3)
|
|
Neuroblastoma
|
3 (1.3)
|
|
Others*
|
37 (16)
|
|
Hematological malignancy
|
|
NHL
|
13 (5.7)
|
|
Multiple myeloma
|
6 (2.6)
|
|
Leukemia
|
4 (1.7)
|
|
HL
|
4 (1.7)
|
|
Follicular lymphoma
|
3 (1.3)
|
|
AML
|
2 (0.9)
|
|
Myelodysplastic syndrome
|
1 (0.4)
|
|
Chemotherapy regimen
|
|
|
Single regimen
|
44 (19.1)
|
|
Doublet regimen
|
139 (60.4)
|
|
Triplet regimen
|
35 (15.2)
|
|
Quadruple regimen
|
12 (5.2)
|
Table 2
Most commonly prescribed chemotherapy regimens
|
Cancer type
|
ICD code
|
Chemotherapy regimen
|
Number of patients (n=230) (%)
|
|
NHL – Non-Hodgkin’s lymphoma; ICD – International Classification of Diseases
|
|
Breast
|
C50.9
|
Doxorubicin + cyclophosphamide
|
18 (36)
|
|
|
Docetaxel + carboplatin
|
7 (14)
|
|
Ovarian
|
C57.9
|
Paclitaxel + carboplatin
|
8 (53.3)
|
|
Stomach
|
C16.9
|
Docetaxel + cisplatin + fluorouracil
|
3 (33.3)
|
|
Esophageal
|
C15.9
|
Paclitaxel + carboplatin
|
8 (34.7)
|
|
|
Epirubicin + oxaliplatin + capecitabine
|
7 (30.4)
|
|
Tongue
|
C02.9
|
Paclitaxel + carboplatin
|
3 (100)
|
|
Buccal mucosa
|
C06.1
|
Cisplatin
|
4 (40)
|
|
|
Paclitaxel + carboplatin
|
4 (40)
|
|
Rectum
|
C21.8
|
Oxaliplatin + capecitabine
|
7 (100)
|
|
Testis
|
C62.9
|
Etoposide + cisplatin
|
2 (100)
|
|
Lung
|
C34.1
|
Pemetrexed + carboplatin
|
9 (52.9)
|
|
Brain
|
C71.9
|
Pemetrexed + carboplatin
|
2 (50)
|
|
|
Bevacizumab
|
2 (50)
|
|
Colon
|
C18.9
|
Oxaliplatin + capecitabine
|
7 (87.5)
|
|
Liver
|
C22.9
|
Gemcitabine + oxaliplatin
|
3 (60)
|
|
NHL
|
C85.80
|
Rituximab + doxorubicin + vincristine + cyclophosphamide
|
9 (69.2)
|
All patients received dexamethasone (100%), and the commonly prescribed antiemetics
were palonosetron (81.3%) followed by ondansetron (66.5%). Out of 230 patients, 193
patients were prescribed with antibiotics to treat infections. Frequently prescribed
antibiotics are levofloxacin (9.6%), sulfamethoxazole and trimethoprim (6.95%), ciprofloxacin
(5.21%), and ofloxacin (5.21%). All the patients were prescribed with ranitidine (100%).
Majority of the patients were prescribed with rabeprazole + domperidone (91.30%) followed
by pantoprazole (34.78%), and 129 patients were prescribed with analgesics in which
majority of them received tramadol + paracetamol (23.91%) followed by morphine (10%)
and diclofenac and paracetamol (9.56%). In this study, 67.39% of the patients were
prescribed filgrastim a granulocyte-colony stimulating factors for prophylaxis and
treatment of chemotherapy-induced myelosuppression. Antihistamines were prescribed
for majority of the patients in all the four cycles of chemotherapy. The most commonly
prescribed supportive care medications are depicted in [Table 3].
Table 3
Most commonly prescribed supportive care medications
|
Supportive care medications
|
ATC code
|
Number of patients, (n=230) (%)
|
|
GCSF – Granulocyte-colony stimulating factor; ATC – Anatomical Therapeutic Chemical
Classification
|
|
Antiemetics
|
|
Dexamethasone
|
A01AC02
|
230 (100)
|
|
Palonosetron
|
A04AA05
|
187 (81.30)
|
|
Ondansetron
|
A04AA01
|
153 (66.52)
|
|
Antibiotics
|
|
Levofloxacin
|
J01MA12
|
22 (9.56)
|
|
Trimethoprim + sulfamethoxazole
|
J01EE01
|
16 (6.95)
|
|
Gastrointestinal drugs
|
|
Ranitidine
|
A02BA02
|
230 (100)
|
|
Rabeprazole + domperidone
|
A02BC54
|
210 (91.30)
|
|
Pantoprazole
|
A02BC02
|
80 (34.78)
|
|
Analgesics
|
|
Tramadol + Paracetamol
|
N02AJ13
|
55 (23.91)
|
|
Morphine
|
N02AA01
|
23 (10)
|
|
GCSFs
|
|
Filgrastim
|
L03AA02
|
155 (67.39)
|
|
Miscellaneous
|
|
Vitamins
|
A11
|
230 (100)
|
|
Chlorpheniramine maleate
|
R06AB04
|
191 (83.04)
|
As per the WHO core drug prescribing indicators, the average number of drugs per prescription
was 9.63. The percentage of antibiotics prescribed was 20.97%. The percentage of drugs
prescribed from the NLEM and the WHO model list of essential medicines was 78.92%
and 80.84%, respectively. The detailed WHO core drug prescribing indicators results
are described in [Table 4].
Table 4
The World Health Organization core drug prescribing indicators
|
WHO core drug prescribing indicators
|
Cycle I
|
Cycle II
|
Cycle III
|
Cycle IV
|
All Cycle
|
|
NLEM – National List of Essential Medicine; WHO – World Health Organization; NLEM
– National List Essential Medicine
|
|
Average number of cytotoxic drugs per prescription
|
2.06
|
2.06
|
2.06
|
2.06
|
2.06
|
|
Average number of drugs per prescription
|
10.25
|
9.59
|
9.35
|
9.36
|
9.63
|
|
Percentage of encounters with an antibiotic prescribed
|
10.86
|
12.17
|
34.78
|
26.08
|
20.97
|
|
Percentage of encounters with an cytotoxic injectable prescribed
|
100
|
100
|
100
|
100
|
100
|
|
Percentage of encounters with an injectable prescribed
|
100
|
100
|
100
|
100
|
100
|
|
Percentage of drugs prescribed from NLEM
|
80.05
|
81.37
|
80.89
|
80.58
|
80.84
|
|
Percentage of drugs prescribed from WHO model list of essential medicines
|
80.58
|
80.92
|
82.33
|
80.95
|
78.92
|
|
Percentage of drugs prescribed by generic name
|
6.82
|
7.88
|
8.50
|
8.8
|
7.98
|
Discussion
Alteration in chemotherapy regimen and supportive care medications is based on the
variability of patients, demographic details, cancer types, and stages of cancer and
depends on the expected toxicities, so it is necessary to evaluate the prescribing
patterns of anticancer and supportive care drugs in cancer patients.
In this study, most of the patients were in the age group of 45–60 years (47%); this
was in correspondence with the study carried out by Catic et al.[11] where 48% of patients were in the age group of 45–60 years. However, contradictory
findings were also observed in a study conducted by Onwusah and Korubo[12] where 19.6% patients were in the age group of 61–70 years. Out of 230 patients,
51.7% were females and 48.3% were males. The study carried out by Manichavasagam et al. reported that females (54.57%) were predominant than the males (45.42%). The present
study is in concurrence with the reference study.[13]
In the present study, majority of the patients were in Stage III of cancer (51.3%)
followed by Stage II (26.5%). Ramalakshmi et al.[3] reported that majority of the cancer patients were in Stage III of cancer (68%)
followed by Stage II (22%). The present study findings are consistent with the previous
study where most of the patients presented with Stage III of cancer.
In the present study, majority of the patients presented with breast cancer (21.7%)
followed by esophagus (10%), lung (7.4%), ovary (6.5%), and other type of cancers.
The study conducted by Pentareddy et al.[5] reported that carcinoma of breast (29.44%) was most commonly observed followed by
carcinoma of head and neck (23.35%) and carcinoma of cervix (17.25%). This study resembles
the previous study that breast cancer was most commonly observed but differs in other
type of cancers.
In the present study, the most commonly prescribed chemotherapy regimen was double
regimen, where pemetrexed and carboplatin were commonly prescribed in lung cancer
(52.9%) followed by doxorubicin and cyclophosphamide in breast cancer (36%), paclitaxel
and carboplatin in carcinoma of esophagus (34.7%), and lung cancer (17.6%). A study
conducted by Pentareddy et al.[5] reported that among the commonly prescribed double therapy, doxorubicin and cyclophosphamide
(51.72%) was mostly prescribed in breast cancer followed by paclitaxel and carboplatin
prescribed in esophagus (50%) and lung cancer (33.3%) whereas pemetrexed and carboplatin
(66.6%) was commonly used in lung cancer. This study was in correspondence with the
previous study where double regimen is commonly prescribed.
Out of 230 patients, all patients received antiemetics include dexamethasone (100%)
followed by palonosetron (81.3%), ondansetron (66.5%), and aprepitant (41.3%) which
was in concurrence with the study conducted by Ramalakshmi et al.,[3] where the majority of patients received dexamethasone and palonosetron (100%), respectively,
followed by aprepitant (8%) and ondansetron (2%).
The most commonly prescribed antibiotics in this study were levofloxacin (9.56%),
followed by trimethoprim and sulfamethoxazole (6.96%). A study carried out by Ramalakshmi
et al.[3] reported that the majority of the patients received azithromycin (27.7%) followed
by clindamycin (22.2%). The present study findings were contradictory to the reference
study.[3]
Out of 230 patients, ranitidine (100%) was prescribed for all patients followed by
rabeprazole and domperidone (91.30%) and pantoprazole (34.78%). A study conducted
by Ramalakshmi et al. stated that all the patients received pantoprazole and sucralfate (100%) followed
by laxatives (30%). The findings of the study were in contrary to the results of the
previous study.[3] Tramadol and paracetamol (23.9%) were the most commonly prescribed analgesics during
different chemotherapy cycles followed by morphine (10%). These findings are in contrary
with the study carried out by Ramalakshmi et al.,[3] where paracetamol (62%) was mostly prescribed followed by aspirin (20%).
The average number of medications per prescription in the study was 9.63. A study
conducted by Mugada et al.[4] reported that the average number of medications per prescription was 8.16 which
is in contrast with the present study since it involves adjuvant therapies such as
antiemetics, analgesics, and gastrointestinal agents for the prevention and management
of expected adverse events.
In the present study, among all four cycles of chemotherapy, the percentage of antibiotics
prescribed was 83.91%, and in the study conducted by Mugada et al.,[4] the percentage of antibiotics prescribed was 54.8% which is less compared to our
study. It might be prescribed only for specific infections.
The percentage of cytotoxic injections and percentage of other injections prescribed
were 100%. A study conducted by Mugada et al.[4] reported that the cytotoxic injections prescribed were 100% and the other injections
were 75.5%, which is greater because the premedication given along with the cytotoxic
drugs is prescribed in injectable form.
The percentage of drugs prescribed from the NLEM and the WHO model list was 80.84%
and 78.92%, respectively, which resembles the study conducted by Mugada et al.,[4] where the percentage of drugs prescribed from the WHO model list was 80.70% while
the NLEM was contrary to the study since EDL was calculated. The percentage of the
drugs prescribed was finite since drugs were given to a particular patient based on
their risk–benefit ratio and for specific infections; so, there will be difference
in percentage of drugs prescribed from the WHO and the NLEM.
The percentage of drugs prescribed in generic name was 7.98%, and in the study conducted
by Mugada et al.,[4] the percentage of drugs prescribed by generic name was 93%, which is limited and
it has to be encouraged since it helps to improve rational prescribing of drugs, to
avoid dispensing errors, and to reduce cost of the therapy, thus reducing the overall
medical expenditure.
Conclusion
In the present study, majority of patients were in the age group of 45–60 years (47%).
Females (51.7%) were predominant than males (48.3%). Most of the patients were in
Stage III (51.3%) and had solid tumor (85.5%); among them, breast cancer (21.7%) was
mostly observed. Doublet chemotherapy regimen (60.4%) was frequently prescribed, in
which 36% of patients who received doxorubicin and cyclophosphamide had carcinoma
of breast while paclitaxel and carboplatin (16.52%) were highly prescribed among the
different cancer types. The most commonly prescribed supportive care medications –
dexamethasone and ranitidine (100%), filgrastim (67.4%), tramadol and paracetamol
(23.91%), and levofloxacin (9.56%) – were prescribed among all four cycles of chemotherapy.
As per the WHO core drug prescribing indicators, the average number of drugs per prescription
was 9.63. The percentage of antibiotics prescribed was 83.91%. The percentage of drugs
prescribed from the NLEM and the WHO model list was 80.84% and 78.92%, respectively.
