Keywords
Adverse drug reactions - cancer - chemotherapy - febrile neutropenia - incidence
Introduction
Cancer is the second most common cause of morbidity and mortality in most countries.
Chemotherapy is an important treatment option in most cancers. Chemotherapy regimens
are associated with variable period of myelosuppression.[1] Chemotherapy suppresses the bone marrow. Thus, neutrophils, white blood cells (WBC),
platelets, and red blood cells which are produced by the bone marrow decrease in count
making the person more vulnerable to infections. Decrease in the count of neutrophils
with fever can lead to a febrile neutropenic condition.[2] Febrile neutropenia (FN) is defined as a “single oral temperature of ≥38.5°C or
sustained temperature of ≥38.0°C over a 1 h period with <500 neutrophils/mm or <1000
neutrophils/mm with a predicted decline to 500 cells/mm over 2 days”. The incidence
and severity are based on the neutrophil count.[3]
A survey of literature states that the incidence of chemotherapy-induced FN (CIFN)
was reported in: paclitaxel and carboplatin (1%), docetaxel and carboplatin (2%),
doxorubicin (3%), paclitaxel (6%), irinotecan and nedaplatin (7%), adriamycin and
cisplatin (11%), docetaxel and gemcitabine (33%), irinotecan and mitomycin C (40%),
etc.[4] The Higher risk of CIFN was observed in patients treated with prophylaxis chemotherapy
regimen. The risk of CIFN can be obtained from the Multinational Association of Supportive
Care in Cancer (MASCC) score and from absolute neutrophil count (ANC). MASCC score
of >21 indicates low risk and <21 indicates high risk of FN.[5] FN is divided into Grades 1-4 based on the ANC counts (cells/mm 3).[6]
The duration of hospitalization is a predictive factor in evaluating the severity
of CIFN. High-dose chemotherapeutic regimen, hematological malignancies, comorbidities,
infections and can upsurge the duration of FN and consequently lead hospitalization.[7] Based on the risk of FN, prophylactic treatment such as granulocyte monocyte colony-stimulating
factors (CSF) or granulocyte CSF (G-CSF) is endorsed as a standard in the chemotherapy
regimen. Antibiotics are also considered as prophylactic agents due to increased vulnerability
to infection and as a treatment option for CIFN.[8] Treatment options for the management of CIFN depend on age, gender, comorbidities,
primary or secondary prophylaxis, the severity of the neutropenia, appropriate prophylactic
use, antibiotics used and the response of the patient to the therapy.[5]
Methods
Study design
A prospective observational study was conducted for a period of 6 months (October
2016–March 2017). This study was conducted in patients admitted to and visiting the
outpatient setting in the Oncology Department of Justice K. S. Hegde Charitable Hospital,
Dakshina Kannada, Deralakatte, Mangaluru.
Ethical approval
The study was approved by the Institutional Ethics Committee (REF: INST. EC/EC/97/2016–2017)
at K. S. Hegde Medical Academy, Mangalore.
Study criteria
The inclusion criteria consisted of patients of all age groups of either gender, all
cancerous patients receiving chemotherapy and who have given the written informed
consent form. Acquired or congenital neutropenic patients, radiation-induced neutropenia
and patients not willing to participate in the study were excluded from the study.
Data collection
Information such as demographics (age, gender, and comorbidities), complaints on admission,
hematological investigations (neutrophil counts, platelet counts, hemoglobin levels,
erythrocyte sedimentation rate [ESR], WBC), type of tumor, cycles and antineoplastic
chemotherapy that cause FN, treatment history, option and outcome data were obtained
from the patients' clinical records. Details necessary for evaluation regarding concomitant
medications, comorbidities, tumor type, stage of cancer, prophylaxis, and dose modification
for causality assessment and management that helps to assess the incidence of CIFN
and their expected outcomes.
All the prescriptions of the study population were screened for CIFN. The details
regarding temperature, length of hospitalization, and laboratory reports were obtained
from the patient's clinical record. Demographics of the patients were studied to find
out the pattern of adverse drug reactions (ADRs).
Identification of chemotherapy-induced febrile neutropenia
All the patients receiving chemotherapy were classified according to MASCC 2013 as
patients at risk for serious complications of FN into high and low risk patients and
CIFN was graded according to ANC.[6]
[9] Patients who met the inclusion criteria were assessed for the incidence, causality
assessment, severity assessment, preventable measures, evaluation of risk factors,
and treatment outcome of CIFN.
Identification of CIFN was done based on regular follow-up of the patients by analyzing
the subjective findings. Consultant oncologist assessed suspected ADRs and relevant
data were filled in the case record form. The details of laboratory manifestations,
medications used were recorded in the case record form and ADR form.
Data of the reported ADRs were evaluated to understand the pattern of the ADRs with
respect to patient demographics, the severity of the reaction, characteristics of
the drug involved, the outcome of the reaction and the management of FN.
Analysis of chemotherapy-induced febrile neutropenia
To assess the likelihood that a drug has caused the reaction, causality assessment
was done using Naranjo scale (1991) which classifies CIFN as certain, probable, possible
and unlikely and the WHO probability scale as certain probable, possible, unlikely,
unclassified and conditional to be drug-induced depending on the level of association.[10]
[11] Depending on the severity, CIFN was classified into mild, moderate, and severe reactions
using the criteria developed by Hartwig et al. and ANC for severity assessment.[9]
[12] CIFN was categorized into definitely preventable, probably preventable and not preventable
using the criteria of Schumock and Thornton modified.[13]
Predisposing factors
Factors that could have predisposed to the occurrence of CIFN in the individual reports
were evaluated. Predisposing factors were generally classified for the study into
age, gender, multiple disease state, and polypharmacy.
Management of chemotherapy induced febrile neutropenia
Management of CIFN was categorized as drug withdrawal, dose reduction, additional
treatment for further complications, and no change in regimen with any additional
treatment. Spontaneous reporting of suspected ADRs by the physician, pharmacist, and
nurse can facilitate prevention of CIFN.
Statistical analysis
Frequency and percentage were used to summarize the categorical variables. Descriptive
statistics such as mean, standard deviation, and median were calculated for continuous
variables. Chi-square test or Fisher's exact test was applied to test the association
between categorical variables. Correlation between the continuous variables were tested
by using Spearman's correlation and tested for its significance by using independent
sample t-test with value P < 0.05 considered as statistically significant. Statistical software was used to
analyze the data. The statistical analysis was performed by using SPSS version 16
(IBM Corp., Armonk, NY, United States of America).
Results
During the study, a total of 200 patients with different types of cancers receiving
chemotherapy regimen were recruited. Out of 200 patients, 19 patients developed 22
episodes of CIFN. The overall occurrence of CIFN during the study was 9.5%. In the
study, age group of 45–60 years (52.63%) exhibited a higher incidence of CIFN compared
to other age groups. The mean age of the patients with and without CIFN was 55.26
± 9.42 and 53.61 ± 12.69 years, respectively, (P = 0.689). Occurrence of CIFN was predominantly higher in males (57.89%) than in females
(42.10%). CIFN patients exhibited significantly less social habits such as smoking,
alcohol use, and substance abuse. Most of the patients who developed CIFN had diabetes
mellitus (15.78%), followed by hypertension (10.52%) and other comorbidities.
Cancer is subdivided into solid and hematological tumors. Solid tumors (73.68%) were
prominent than hematological (26.31%) in patients who developed CIFN. Most of the
patients in this study were diagnosed with stage III of cancer (44%), and among the
19 CIFN cases, patients diagnosed at stage III showed a higher incidence of CIFN (42.10%)
than the other stages. Out of 200 patients, 9.5% of the patients developed a fever
along with neutropenia. All these 9.5% of the patients were CIFN (n = 19). The median length of hospital stay for CIFN patients (n = 19) was 6 days and the interquartile (Q3–Q1) ranged from 15 to 10 days. Prophylaxis
is commonly administered along with chemotherapy regimens to prevent CIFN. Out of
200 patients, 155 received G-CSF as prophylaxis and 45 were not. Levofloxacin was
the only antibiotic given as prophylaxis in 3 patients who were at high risk. Among
the 19 CIFN cases reported, 17 patients showed the incidence of CIFN even though they
received G-CSF as prophylaxis. The details regarding the characteristics of CIFN are
summarized in [Table 1]. Among the 19 CIFN patients, 10.52% were in low risk and 89.47% were in high-risk
category based on MASCC. In the ANC analysis, higher incidence of CIFN was exhibited
in Grade 1: Cycle 4 (78.94%), Grade 2: Cycle 1 and 2 (10.52%), Grade 3: Cycle 3 (15.78%),
and Grade 4: Cycle 6 (42.10%). The details regarding the predictors of risk assessment
are depicted in [Table 2]. Out of 200 patients, majority of the patients received double regimen chemotherapy.
Out of 22 episodes of CIFN, double regimen patients developed higher incidence of
CIFN (59.1%). Out of 19 patients, the first (36.36%) and second (22.72%) cycles of
chemotherapy exhibited higher incidence of CIFN cases compared to other chemotherapy
cycles. The details regarding the chemotherapy regimens and cycle are summarized in
[Table 3].
Table 1
Characteristics of patients with and without chemotherapy induced febrile neutropenia
|
Category
|
Patients with CIFN (n=19), n (%)
|
Patients without CIFN (n=181), n (%)
|
P
|
Total number of patients (n=200), n (%)
|
|
DM - Diabetes mellitus; HTN - Hypertension; CKD - Chronic kidney diseases; CLD - Chronic
liver disease; IHD - Ischaemic heart disease; CIFN - Chemotherapy induced febrile
neutropenia
|
|
Age group
|
|
|
|
|
|
<30
|
-
|
8 (4.41)
|
0.689
|
8 (4)
|
|
30-45
|
3 (15.78)
|
38 (20.99)
|
|
41 (20.5)
|
|
45-60
|
10 (52.63)
|
82 (45.30)
|
|
92 (46)
|
|
60-75
|
6 (31.57)
|
46 (25.41)
|
|
52 (26)
|
|
<75
|
-
|
7 (3.86)
|
|
7(3.5)
|
|
Gender
|
|
|
|
|
|
Male
|
11 (57.89)
|
95 (52.5)
|
0.58
|
106 (53)
|
|
Female
|
8 (42.10)
|
86 (47.5)
|
|
94 (47)
|
|
Social habits
|
|
|
|
|
|
Smoking
|
3 (15.78)
|
22 (12.15)
|
-
|
25 (1.25)
|
|
Alcohol
|
2 (10.52)
|
223 (12.70)
|
|
25 (1.25)
|
|
Substance use
|
1 (5.26)
|
4 (2.20)
|
|
5 (2.5)
|
|
Smoking and alcohol
|
|
13 (7.18)
|
|
13 (6.5)
|
|
Smoking, alcohol and substance use
|
1 (5.26)
|
1 (0.55)
|
|
2 (1)
|
|
No social habits
|
15 (78.94)
|
144 (79.55)
|
|
159 (79.5)
|
|
Comorbidities
|
|
|
|
|
|
HTN
|
2 (10.52)
|
29 (16.02)
|
0.40
|
31 (15.5)
|
|
DM
|
3 (15.78)
|
18 (9.94)
|
0.40
|
21 (10.5)
|
|
Asthma
|
2 (10.52)
|
8 (4.41)
|
0.07
|
10 (5)
|
|
CLD
|
-
|
1 (1.81)
|
0.94
|
1 (0.5)
|
|
IHD
|
-
|
2 (1.1)
|
0.89
|
2 (1)
|
|
CKD
|
-
|
1 (1.81)
|
0.94
|
1 (0.5)
|
|
Tumor type
|
|
|
|
|
|
Solid
|
14 (73.68)
|
165 (91.13)
|
-
|
179 (89.5)
|
|
Hematological
|
5 (26.31)
|
16 (8.83)
|
|
21 (10.5)
|
|
Stages of cancer
|
|
|
|
|
|
Stage I
|
3 (15.78)
|
6 (3.31)
|
-
|
9 (4.5)
|
|
Stage II
|
3 (15.78)
|
48 (26.51)
|
|
51 (25.5)
|
|
Stage III
|
8 (42.10)
|
82 (45.30)
|
|
88 (44)
|
|
Stage IV
|
5 (26.31)
|
45 (24.86)
|
|
50 (25)
|
|
Length of hospital stay
|
|
|
|
|
|
1-5
|
8 (42.10)
|
181 (100)
|
0.00
|
189 (94.5)
|
|
5-10
|
7 (36.84)
|
-
|
|
7 (3.5)
|
|
10-15
|
1 (5.26)
|
-
|
|
1 (0.5)
|
|
15-20
|
2 (10.52)
|
-
|
|
2 (1)
|
|
20-25
|
1 (5.26)
|
-
|
|
1 (0.5)
|
|
Prophylaxis
|
|
|
|
|
|
No prophylaxis
|
2 (10.52)
|
43 (23.7)
|
0.001
|
45 (22.5)
|
|
Filgrastim
|
13 (68.42)
|
118 (65.19)
|
|
131 (65.5)
|
|
Peg - filgrastim
|
4 (21.05)
|
20 (11.04)
|
|
24 (12)
|
Table 2
Predictors for risk assessment in patients with and without chemotherapy induced febrile
neutropenia
|
Category
|
Patients with CIFN (n=19), n (%)
|
Patients without CIFN (n=181), n (%)
|
|
MASCC - Multinational association for supportive care in cancer; ANC - Absolute neutrophil
count; CIFN - Chemotherapy induced febrile neutropenia
|
|
MASCC score
|
|
|
|
Low risk
|
2 (10.52)
|
99 (54.69)
|
|
High risk
|
17 (89.47)
|
82 (45.30)
|
|
ANC
|
|
|
|
Grade 1
|
|
|
|
Cycle 1
|
10 (52.63)
|
180 (99.44)
|
|
Cycle 2
|
13 (68.42)
|
180 (99.44)
|
|
Cycle 3
|
13 (68.42)
|
179 (98.89)
|
|
Cycle 4
|
15 (78.94)
|
179 (98.89)
|
|
Cycle 5
|
12 (63.17)
|
155 (85.63)
|
|
Cycle 6
|
9 (47.36)
|
150 (82.87)
|
|
Grade 2
|
|
|
|
Cycle 1
|
2 (10.52)
|
-
|
|
Cycle 2
|
2 (10.52)
|
-
|
|
Cycle 3
|
-
|
2 (1.10)
|
|
Cycle 4
|
-
|
2 (1.10)
|
|
Cycle 5
|
-
|
-
|
|
Cycle 6
|
1 (5.26)
|
1 (0.55)
|
|
Grade 3
|
|
|
|
Cycle 1
|
-
|
1 (0.55)
|
|
Cycle 2
|
-
|
-
|
|
Cycle 3
|
3 (15.78)
|
-
|
|
Cycle 4
|
1 (5.26)
|
-
|
|
Cycle 5
|
1 (5.26)
|
1 (0.55)
|
|
Cycle 6
|
1 (5.26)
|
-
|
|
Grade 4
|
|
|
|
Cycle 1
|
7 (36.84)
|
-
|
|
Cycle 2
|
4 (21.05)
|
1 (0.55)
|
|
Cycle 3
|
3 (15.78)
|
-
|
|
Cycle 4
|
3 (15.78)
|
-
|
|
Cycle 5
|
6 (31.57)
|
25 (13.81)
|
|
Cycle 6
|
8 (42.10)
|
30 (16.57)
|
Table 3
Chemotherapy regimen and cycle in chemotherapy induced febrile neutropenia patients
|
Category
|
Frequency (n=22), n (%)
|
|
Chemotherapy regimens
|
|
|
Single regimen
|
7 (31.8)
|
|
Azacitidine
|
4 (57.14)
|
|
Paclitaxel
|
1 (14.28)
|
|
Bendamustine
|
1 (14.28)
|
|
Decitabine
|
1 (14.28)
|
|
Double regimen
|
13 (59.1)
|
|
Irinotecan + capecitabine
|
1 (7.69)
|
|
Etoposide + carboplatin
|
3 (23.07)
|
|
Doxorubicin + capecitabine
|
1 (7.69)
|
|
Gemcitabine + docetaxel
|
1 (7.69)
|
|
Gemcitabine + carboplatin
|
1 (7.69)
|
|
Epirubicin + oxaliplatin
|
1 (7.69)
|
|
Paclitaxel + carboplatin
|
3 (23.07)
|
|
Docetaxel + carboplatin
|
2 (15.38)
|
|
Triple regimen
|
1 (4.5)
|
|
Vincristine + doxorubicin +
|
1 (4.5)
|
|
cyclophosphamide
|
|
|
Quadruple regimen
|
1 (4.5)
|
|
Adriamycin + bleomycin +
|
1 (4.5)
|
|
vinblastine+dacarbazine
|
|
|
Chemotherapy cycles
|
|
|
Cycle 1
|
8 (36.36)
|
|
Cycle 2
|
5 (22.72)
|
|
Cycle 3
|
3 (13.63)
|
|
Cycle 4
|
1 (4.54)
|
|
Cycle 5
|
1 (4.54)
|
|
Cycle 6
|
4 (18.18)
|
Causality, severity, preventability, and predictability of chemotherapy-induced febrile
neutropenia
The WHO probability scale was used to analyze the suspected CIFN and the scale showed
that 81.81% of CIFN reactions were probably followed by certain (13.63%) and possible
(4.54%). To assess the causality of the suspected CIFN, Naranjo's causality assessment
scale was used. The scales showed that 77.27% of CIFN were probable followed by 13.63%
were certain and 9.09% were possible. Severity assessment scale was used to classify
the intensity of CIFN cases. Mortality rate due to CIFN among the 19 patients were
2 (%). Majority of the CIFN cases had moderate (level 4a) scale of severity (36.36%).
Preventability assessment for CIFN was done using Schumock and Thornton scale. The
scale showed that 27.27% of CIFN were not preventable and 72.72% were probably preventable.
All the 22 episodes of CIFN reported were predictable. Among 19 CIFN patients, 40.90%
of drugs were withdrawn, 4.5% of doses were altered, and 54.54% had no change. Majority
of the CIFN cases were treated specifically (86.36%) and few were treated symptomatically
(13.63%), Outcome of the patients depends on the intensity of the reaction. Majority
of the CIFN patients were recovered 59.09% and the others ceasing the drug that has
caused the reaction can confirm the causative agent. In this study, out of 22 CIFN
reactions, 12 (54.53%) were dechallenged. Reintroducing the drug can identify the
causative drug that has caused CIFN. Out of 22 CIFN reactions, 6 (27.26%) were rechallenged.
The details regarding the assessment of CIFN are depicted in [Table 4]. Majority of the patients had breast cancer (18.5%), but FN was mostly observed
in patients diagnosed with stomach cancer (15.7%). Out of the 19 CIFN patients, 16
experienced FN once whereas 3 of them experienced FN twice. The regimen that caused
FN twice were Carboplatin-Etoposide, Carboplatin-Placlitaxel and Adriamycin + Bleomycin
+ Vincristine + Dacarbazine regimen. The detailed description of cancer with chemotherapy
regimen in patients with and without FN is depicted in [Table 5].
Table 4
Causality, severity, preventability and predictability of chemotherapy induced febrile
neutropenia
|
CIFN - Chemotherapy induced febrile neutropenia
|
|
WHO scale, n (%)
|
|
|
Certain
|
3 (13.63)
|
|
Probable
|
18 (81.81)
|
|
Possible
|
1 (4.54)
|
|
Unlikely
|
-
|
|
Unclassified
|
-
|
|
Conditional
|
-
|
|
Naranjo’s scale, n (%)
|
|
|
Certain
|
3 (13.63)
|
|
Probable
|
17 (77.27)
|
|
Possible
|
2 (9.09)
|
|
Unlikely
|
-
|
|
Hartwig’s severity scale, n (%)
|
|
|
Level 1
|
2 (9.09)
|
|
Level 2
|
1 (4.54)
|
|
Level 3
|
3 (13.63)
|
|
Level 4a
|
8 (36.36)
|
|
Level 4b
|
5 (22.72)
|
|
Level 5
|
1 (4.54)
|
|
Level 6
|
-
|
|
Level 7
|
2 (9.09)
|
|
Preventability scale, n (%)
|
|
|
Definitely preventable
|
-
|
|
Probably preventable
|
16 (72.72)
|
|
Not preventable
|
6 (27.27)
|
|
Predictability scale, n (%)
|
|
|
Predicatble
|
22 (100)
|
|
Not predictable
|
-
|
|
Management of CIFN, n (%)
|
|
|
Drug withdrawan
|
9 (40.90)
|
|
Dose altered
|
1 (4.54)
|
|
No change
|
12 (54.54)
|
|
Treatment of CIFN, n (%)
|
|
|
Specific
|
19 (86.36)
|
|
Symptomatic
|
3 (13.63)
|
|
Nil
|
-
|
|
Outcome of CIFN, n (%)
|
|
|
Fatal
|
2 (9.09)
|
|
Recovery
|
13 (59.1)
|
|
Continuing
|
7 (31.8)
|
|
Dechallenge (n=12), n (%)
|
|
|
Definite improvement
|
3 (25)
|
|
No improvement
|
5 (41.6)
|
|
Unknown
|
4 (33.3)
|
|
Rechallenge (n=6), n (%)
|
|
|
Recurrence of symptoms
|
-
|
|
No occurrence of symptoms
|
3 (50)
|
|
Unknown
|
3 (50)
|
Table 5
Types of cancer and chemotherapy regimen administered in patients with and without
chemotherapy induced febrile neutropenia
|
Cancer types
|
Chemotherapy regimen
|
Patients with FN Patients without FN (n=19), n (%) (n=181), n (%)
|
|
*Most commonly reported in the literature and observed in the study. AML - Acute myeloid
leukemia; MDS - Myelodysplastic syndrome; NHL - Non-Hodgkin lymphoma; DLBL - Diffuse
large B-cell lymphoma; FN - Febrile neutropenia
|
|
Solid
|
|
|
|
|
Breast
|
Doxorubicin + cyclophosphamide
|
-
|
27 (14)
|
|
Paclitaxel
|
1 (5.2)
|
9 (4.9)
|
|
Stomach
|
Oxaliplatin
|
-
|
5 (2.7)
|
|
Epirubicin + oxaliplatin
|
1 (5.2)
|
6 (3.3)
|
|
Docetaxel + capecitabine
|
-
|
4 (2.2)
|
|
Docetaxel + carboplatin
|
2 (10.5)
|
2 (1.1)
|
|
Epirubicin + oxaliplatin + capecitabine
|
-
|
5 (2.7)
|
|
Epirubicin + 5-flurouracil + cisplatin
|
-
|
2 (1.1)
|
|
Lung
|
Carboplatin + etoposide
|
2 (10.5)
|
8 (4.4)
|
|
Pemetrexed + carboplatin
|
-
|
6 (3.3)
|
|
Gemcitabine + carboplatin
|
-
|
4 (2.2)
|
|
Ovary
|
Bevacizumab
|
-
|
2 (1.1)
|
|
Liposomal Doxorubicin + carboplatin
|
-
|
6 (3.3)
|
|
Gemcitabine + carboplatin
|
1 (5.2)
|
4 (2.2)
|
|
Carboplatin + paclitaxel
|
1 (5.2)
|
6 (3.3)
|
|
Rectum
|
Oxaliplatin + capecitabine
|
-
|
12 (6.6)
|
|
Oropharynx
|
Carboplatin + paclitaxel
|
-
|
15 (8.2)
|
|
Colon
|
Oxaliplatin
|
-
|
3 (1.6)
|
|
Oxaliplatin + capecitabine
|
-
|
5 (2.7)
|
|
Irinotecan + capecitabine
|
1 (5.2)
|
2 (1.1)
|
|
Gall bladder
|
Gemcitabine + carboplatin
|
-
|
7 (3.8)
|
|
Neuroendocrine
|
Oxaliplatin + capecitabine
|
1 (5.2)
|
3 (1.6)
|
|
Esophageal
|
Carboplatin + paclitaxel
|
1 (5.2)
|
3 (1.6)
|
|
Bladder
|
Cisplatin + gemcitabine
|
-
|
2 (1.1)
|
|
Gemcitabine + carboplatin
|
-
|
2 (1.1)
|
|
Pancreas
|
Gemcitabine + oxaliplatin
|
-
|
3 (1.6)
|
|
Larynx
|
Cisplatin
|
-
|
3 (1.6)
|
|
Soft tissue sarcoma
|
Gemcitabine + docetaxel
|
1 (5.2)
|
2 (1.1)
|
|
Postate
|
Docetaxel
|
-
|
2 (1.1)
|
|
Gliblastoma multiforme
|
Bevacizumab
|
-
|
2 (1.1)
|
|
Ewings sarcoma
|
Etoposide + ifosfamide
|
-
|
2 (1.1)
|
|
Cervix
|
Cisplatin
|
-
|
1 (0.55)
|
|
Paclitaxel + carboplatin
|
1 (5.2)
|
-
|
|
Haematological
|
|
|
|
|
AML
|
Azacitidine*
|
3 (15.7)
|
1 (0.55)
|
|
MDS
|
Decitabine*
|
1 (5.2)
|
-
|
|
Follicular lymphoma
|
Bendamustine + rituximab
|
-
|
2 (1.1)
|
|
NHL
|
Rituximab + doxorubicin + vincristine +cyclophosphamide + prednisolone
|
-
|
3 (1.6)
|
|
Doxorubicin + vincristine + cyclophosphamide + prednisolone
|
1 (5.2)
|
1 (0.55)
|
|
Ann arbor
|
Adriamycin + bleomycin + vincristine + dacarbazine
|
1 (5.2)
|
2 (1.1)
|
|
Multiple myeloma
|
Bendamustine
|
1 (5.2)
|
1 (0.55)
|
|
Bortezomib + cyclophosphamide
|
-
|
2 (1.1)
|
|
Hodgkin lymphoma
|
Adriamycin + bleomycin + vincristine + dacarbazine
|
-
|
2 (1.1)
|
|
DLBL
|
Rituximab + doxorubicin + vincristine + cyclophosphamide + prednisolone
|
-
|
2 (1.1)
|
Discussion
The development of myelosuppression during chemotherapy is influenced by the demographics
of the patients (age, gender, and comorbidities), cancer types, stages, and characteristics
of the chemotherapy regimen used.
Higher incidence of CIFN was exhibited in the age group between 45 and 60 years (52.63%)
among 19 CIFN patients compared to other groups. In a study conducted by Catic et al., higher incidence of CIFN was observed in the age group of 41–60 years (48%) among
27 CIFN patients.[14] The present study is in concurrence with the Catic et al., study, where the results showed a higher incidence of CIFN in the age group of
40–60 years.[14]
Out of 19 CIFN patients, 57.89% of patients were male and 42.10% were female. A study
conducted by Sammut and Mazhar et al., analyzed 32 CIFN cases in which 62.5% were female and 37.5% were male.[15] The present study was contradictory to the reference study. In the present study,
solid tumors exhibited higher incidence of CIFN (73.68%) than hematological tumors
(26.31%). In a study conducted by Ahn et al., out of 396 episodes of CIFN, solid tumors (71.5%) were predominantly more than
hematological (28.5%).[9] Hence, this study is in agreement with the previous study were solid tumors shows
higher CIFN events.
Out of 200 patients, majority of the patients received double regimen chemotherapy
(59.1%) and showed higher incidence of CIFN. In a study conducted by Hashiguchi et al., among 291 patients, the most common chemotherapy was paclitaxel and carboplatin
(double regimen) which exhibited 50.5% of CIFN cases.[4] Hence, the present study resembles the previous study that double regimen shows
higher incidence of CIFN. The median length of stay for patients who developed CIFN
was 6 days. The P value was 0.00, which showed strong association between length of hospitalization
and the development of CIFN. The study conducted by Weycker et al., reported that the median length of stay was 8.14 days for patients with CIFN.[16] The incidence of CIFN in each cycles varied, 36.63% were encountered in cycle 1
followed by 22.72% and 18.18% in cycle 2 and cycle 6, respectively. Culakova et al., reported 9.7% of CIFN in cycle 1 followed by 5.7% and 3.8% in cycle 2 and 3, respectively.[17] The present study is in correspondence with the previous study that incidence is
more in cycle 1 and 2, but varied in the following cycles.
The MASCC risk index score was used to predict the risk of CIFN among the patients
(n = 200), 50.5% of them were in low risk and 49.5% of them were in high-risk category
of patients. Of the high-risk patients, 89.47% developed CIFN and 10.52% developed
CIFN in low-risk patients. The P value for MASCC score was 0.001, which showed strong association with the risk of
developing CIFN. A study conducted by Ahn et al., showed 90% of low-risk patients and 72% of high risk patients using MASCC risk
index score, where 18.9% of high risk died.[9] Hence, this study is in correspondence with the previous study that MASCC score
is used to predict low and high-risk patients. The incidence of CIFN in the study
was 9.5%, similarly Shiota et al., conducted a study on 37 patients and the incidence of CIFN was 10.8%.[18]
The higher incidence of CIFN was shown in Stage 3 of cancer (42.10%), similarly Talwar
et al., conducted a study, where most of the patients with CIFN presented in stage 3 (33.2%)
and in Stage 4 (41.6%) of cancer.[19] To the best of our knowledge, this is the premier study to analyze the CIFN reactions
by using causality, severity, preventability, and predictability scales. As per the
WHO and Naranjo's scales, most of the CIFN reactions were classified as probably 81.82%
and 77.2%, respectively. Out of 22 CIFN cases, 9.09% of mortality has been reported,
and all the CIFN reactions were predictable. Preventability assessment scale showed
that 27.27% of reactions are not preventable and 72.72% reactions are probably preventable.
As management of CIFN among 19 patients, 40.90% of drugs were withdrawn, 4.5% of doses
were altered, and 54.54% had no change. In addition, 86.36% were treated specifically
whereas, 13.63% were treated symptomatically. Moreover, 50.09% of patients recovered,
whereas 22.72% of patients continued in the same condition and 18.18% were fatal.
The percentage of patients underwent dechallenge were 54.53% and rechallenge were
27.26%.
Conclusions
In this study, the incidence of CIFN was 9.5%. The age group of 45–60 years (52.63%)
showed higher incidence of CIFN compared to another age group. In gender-wise distribution,
the occurrence of CIFN was predominantly higher in males (57.89%) than in females
(42.10%). The patients diagnosed at stage 3 showed greater incidence of CIFN (42.10%)
than the other stages. The solid tumors (73.68%) were prominent than hematological
tumor (26.31%). The length of hospitalization had prolonged for all patients who developed
CIFN with a median of 6 days. The patients who received double chemotherapy regimen
(59.1%) showed a higher incidence of CIFN than the other chemotherapy regimens. The
incidence of CIFN was higher in I and II cycles of chemotherapy showed 36.36% and
22.72%, respectively.
