Incidence of Anaemia and Thrombocytopenia Following Breast Cancer Chemotherapeutic Regimens AC-T, AC-T+ Ca, and AC-T+Tr IN in a Tertiary Care Center

doi:10.21203/rs.3.rs-4876309/v1

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Incidence of Anaemia and Thrombocytopenia Following Breast Cancer Chemotherapeutic Regimens AC-T, AC-T+ Ca, and AC-T+Tr IN in a Tertiary Care Center

https://doi.org/10.21203/rs.3.rs-4876309/v1

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BACKGROUND: In breast cancer, the most common regimen used for the neoadjuvant and adjuvant nonmetastatic setting is 4 cycles of adriamycin and cyclophosphamide followed by docetaxel, docetaxel + trastuzumab, docetaxel, and carboplatin. (1)

Patients with breast cancer were treated with three different chemotherapeutic regimens, namely, AC-T (adriamycin and cyclophosphamide followed by docetaxel) regimen I, AC-T+Ca (adriamycin and cyclophosphamide followed by docetaxel and carboplatin) regimen II, and AC-T+Tr (adriamycin and cyclophosphamide followed by docetaxel and trastuzumab) regimen III, at a tertiary care hospital. Of these, myelosuppression was the major concern in treatment follow-ups. Here, I reviewed the incidence and management of anemia during the post-chemotherapy period.

METHODS: A prospective open-label observational comparative study was performed to evaluate the incidence of anemia and thrombocytopenia among three regimens, namely, the chemotherapy regimen AC-T, Regimen II AC-T+Ca, and Regimen III AC-T+Tr. All enrolled patients received pegfilgrastim/filgrastim prophylactically or as a part of the case of myelosuppression. The regimen I enrolled and completed a study of 38 patients, regimen II 40 patients, and regimen III 46 patients. All patients were subjected to statistical analysis using SPSS.

RESULTS: A total of 882 (88.9%) episodes of anemia (all grades) were observed among a total of 992 cycles of chemotherapy. Twenty-seven patients in Regimen I and II and 31 patients in Regimen III had at least one episode of anemia (grade 2 or above) during their chemotherapy cycles. Overall, 293 episodes were Grade 2, 21 episodes were Grade 3, and 3 episodes were Grade 4 anemia among the 3 study regimens. The mean incidence of anemia in regimen I in the initial 4 cycles was 3.4+/- 1.1, in the final 4 cycles, it was 3.7± 0.6, and in the overall 8 cycles was 7.1± 1.5. In regimen II, as in the initial 4 cycles:3.5+0.8, in the final 4 cycles: 3.9+0.4, and in the overall 8 cycles:7.4+1.1. In regimen III, as in the initial 4 cycles: 3.3+1; in the final 4 cycles: 3.7+ 0.6; and in the overall 8 cycles: 7.1+1.5. The mean incidence of all grades of anemia was comparable among the 3 study regimens, with a mean incidence of 7.1 in regimen I, 7.4 in regimen II, and 7.1 in regimen III over 8 cycles of chemotherapy. There was no statistically significant difference in the mean incidence of anemia among the 3 study groups.

A total of 109 episodes of thrombocytopenia out of 992 cycles of chemotherapy (10.9%) were observed. In the initial 4 cycles of chemotherapy, 44 episodes occurred, and in the final 4 cycles, 65 episodes occurred. Grade 2 or above thrombocytopenia resulting from at least one episode during the treatment period was reported in 6 patients in regimen I, 5 patients in regimen II, and 1 patient in regimen III. Of the total thrombocytopenia grades 2 and above, only 6 episodes in regimen I, 5 episodes in regimen II, and 2 episodes in regimen III were noted. The mean incidence of thrombocytopenia in regimen I in the initial 4 cycles: 0.1+ 0.5; in the final 4 cycles: 0.2+ 0.6, and in the overall 8 cycles: 0.3+ 1. In regimen II, the initial 4 cycles, were 0.1+ 0.3; in the final 4 cycles0.3+0.6; and in the overall 8 cycles, 0.4+0.7. In regimen III, as in the initial 4 cycles:0+0; in the final 4 cycles: 0.1+ 0.4; and in the overall 8 cycles:0.1+0.4. The mean incidence of thrombocytopenia of all grades was comparable among the 3 study regimens, with 0.3 in regimen I, 0.4 in regimen II, and 0.1 in regimen III over 8 cycles of chemotherapy. There was no statistically significant difference in the mean incidence of thrombocytopenia among the 3 study regimens.

CONCLUSION: There was no significant difference in the incidence of anemiaamong the 3 regimens in the initial 4 chemo cycles, final 4 chemo cycles, or overall 8 cycles of chemotherapy. There was a statistically significant difference in the mean incidence of thrombocytopenia during the initial 4 cycles of chemotherapy among the 3 regimens. However, among the overall 8 cycles of chemotherapy, there was no statistically significant difference in the mean incidence of thrombocytopenia among the three regimens. A trend towards a decrease in the mean Hb value was observed towards later cycles of chemotherapy in the overall study population due to the cumulative toxicity of chemotherapy regimens in the bone marrow.

Oncology

Clinical Pharmacology

Anemia

Thrombocytopenia

Adriamycin

Chemotherapy

Breast Cancer

Breast cancer is a common cause of malignancy in the female population worldwide(1, 2). It is a heterogeneous disease resulting from many factors, such as the progressive accumulation of genetic aberrations, including point mutations, chromosomal amplifications, deletions, rearrangements, and translocations(2). Treatment for breast cancer consists of multiple modalities, namely surgery, chemotherapy, radiation therapy, and biological therapy. Anthracycline-based chemotherapeutic regimens are commonly used(1, 2).

Three common regimens used for therapeutic purposes in breast cancer treatment are Adriamycin chemotherapy regimen and cyclophosphamide(AC), followed by docetaxel(AC-T) (Regimen I); AC, followed by docetaxel and carboplatin (AC-T + Carboplatin)(Regimen II) ; and AC followed by docetaxel and trastuzumab (AC-T + Tr) (Regimen III), which are administered to patients with stage 0 to stage 3 disease.

In a phase 11 trial of docetaxel and carboplatin-based neoadjuvant chemotherapy for stage II/111 breast cancer, a differential response was observed, with the highest pCR rate achieved in patients with TNBC(3). The Hematological adverse drug reactions associated with anthracycline-based chemotherapy regimens include neutropenia, anemia, thrombocytopenia, and, rarely, leukemia(5, 6, 7, 8). Along with docetaxel and carboplatin regimens, more myelosuppression has been noted(6). When docetaxel is given in combination with doxorubicin, an increased incidence of myelosuppression and gastrointestinal side effects has been reported(6). Myelosuppression is a dose-limiting side effect. Myelosuppression is more severe and prolonged in patients with impaired renal function. Leukopenia, thrombocytopenia, and anemia occur in patients taking carboplatin(6).

According to a study involving 710 patients, myelosuppression was the dose-limiting toxicity of carboplatin, leukopenia occurred in 55% of patients, and leukopenia and thrombocytopenia resulted in symptomatic events such as infection and bleeding in a minority of patients. Anemia was frequent (59%) and required transfusion support in one-fifth of the patients(6, 12). There is an increased incidence of leucopenia, thrombocytopenia, anemia, and febrile neutropenia when trastuzumab is given with chemotherapy, but it infrequently causes myelosuppression when used alone(6).

In cyclophosphamide-containing chemotherapeutic regimens, the major dose-limiting side effect is myelosuppression. After a single dose, the white blood cell count may reach its nadir within approximately 1–2 weeks, and full recovery usually occurs within approximately 3–4 weeks. Thrombocytopenia and anemia may occur but tend to be less common and less severe(6).

This study aimed to analyze the incidence of anemia and thrombocytopenia among patients treated with three chemotherapeutic regimens for breast cancer in a tertiary care center. In Regimens I, II, and III, patients were treated with an initial 4 cycles of AC followed by the next 4 cycles of docetaxel, docetaxel + carboplatin, and docetaxel + trastuzumab respectively. All patients received prophylactic pegfilgrastim and filgrastim for treatment in the oncology department of a tertiary care center. The incidence of anemia and thrombocytopenia following chemotherapy was measured by recording hemoglobin and platelet count on the 7th day after chemotherapy as a routine procedure. The Case report form was entered regularly in a structured format throughout the study period. The present study included a prospective open-label comparative cohort. The study was initiated only after ethical committee approval was obtained from the institution. The duration of the study ranged from January 2016 to January 2017. A total of 41 patients were enrolled in each study arm.

It is calculated by the formula

N = 2 pq (Zcrit + Zpwr) 2/D

Inclusion criteria

Patients with normal cognition

Patients with breast malignancies aged 18–65 years and with stage 1–3 disease

G-CSF support was obtained (Pegfilgrastim/Filgrastim).

Absolute neutrophil count > 1.5x109/l

Platelet count > 100x109/l

Serum creatinine < 2

Serum total bilirubin < 1.5 times the upper limit of normal

Exclusion criteria

Stage 4 metastatic patients

Concurrent other malignancies

Cardiac failure, and myocardial infarction in the past 1 year

Pregnancy and Nursing population

Prior bone marrow transplantation or stem cell therapy

Written informed consent was obtained from all the study subjects before starting the study in the vernacular language.

Study procedure

After screening, patients who fulfilled the inclusion criteria were enrolled in the study. Patients were divided into three groups, patients who underwent chemotherapy regimen I, patients who received chemotherapy regimen II, and patients who received chemotherapy regimen III. AC was followed by docetaxel in regimen I. AC was followed by docetaxel and carboplatin in regimen II. AC followed by docetaxel and trastuzumab in regimen III. A total of 132 patients were screened for the study, and those who satisfied the inclusion criteria were included in the study. Forty-two patients received regimen I,42 patients received regimen II, and 48 patients in the third group received regimen III. In Regimen I, 4 patients were included, and in Regimen II and III, 2 patients each dropped out of the study; hence, Regimen I included 38 patients, Regimen II 40 patients, and Regimen III included 46 patients for final statistical analysis.

Dosage and administration

AC-docetaxel regimen

The initial regimen consisted of 4 cycles of doxorubicin (60 mg/m2) and cyclophosphamide (600mg/m2) every 3 weeks, followed by a final of 4 cycles of docetaxel (100mg/m²) every 3 weeks(9, 10).

AC-docetaxel and carboplatin regimen

The initial regimen consisted of 4 cycles of doxorubicin (60 mg/m2) and cyclophosphamide (600mg/m2) every 3 weeks, and the final regimen consisted of 4 cycles of chemotherapy combined with carboplatin and docetaxel. Carboplatin dose: AUC of 6 intravenously on day 1. Docetaxel: 75 mg/m2 intravenously on day 1. Each chemotherapy cycle was repeated every 21 days(11).

AC-docetaxel and trastuzumab regimen

The initial 4-cycle AC regimen was followed by a final 4-cycle chemotherapy regimen comprising docetaxel and trastuzumab. The docetaxel dose was 75 mg/m2 intravenously on day 1, the trastuzumab dose was 4 mg/kg intravenously, and the dose was subsequently 2 mg/kg intravenously weekly. Chemotherapy was repeated every 21 days for a total of 8 cycles(11).

Dosage of Peg filgrastim/Filgrastim for neutropenia associated with myelosuppressive chemotherapy:

Subcutaneous administration of 5 mcg/kg/day is preferred over the intravenous route until the absolute neutrophil count is 2–3 x 109/mcl or for up to 14 days. Pegylated filgrastim was administered (6 mg) subcutaneously once per chemotherapy cycle.

OUTCOME ASSESSMENT

Established number of patients with anemia and thrombocytopenia of all grades documented and recorded in the prescribed format for assessment during the 8 cycles of chemotherapy before and after chemotherapy for evaluating the different grades of chemotherapy-induced anemia and thrombocytopenia

Statistical analysis

Statistical analysis was performed using Statistical Package for Social Science (SPSS) software version 22. For quantitative data with non-normal distribution used Kruskal-Wallis test, and descriptive statistics with mean, and standard deviation were used for the representation of the baseline and demographic data. Wilcoxon signed-rank test for the paired comparison of the non-normally distributed quantitative data.

Baseline demographic features:

The mean age of the patients was 49.06+/-8.6 years(standard deviation), the minimum age was 26 years, the maximum age was 65 years, the body surface area was 1.58 m² +/- 0.14(SD), the mean baseline hemoglobin level was 11.95 gm/dl +/- 1.36(SD), and the mean baseline platelet count was 3.21lak/dl+/-0.09 (SD) in the overall study population. Twenty- five percent of patients received neoadjuvant treatment and 75% received adjuvant treatment.

Incidence of anemia in patients receiving different chemotherapy regimens:

Table 1

**The pattern of incidence of patient-wise anemia and the cycle of chemotherapy-wise anemia and thrombocytopenia of Grade 2 and above in three different regimens of breast cancer** Pattern of distribution of anemia: **882** (88.9%) episodes of anemia(all grades) out of a total of 992 cycles of chemotherapy were observed. Twenty-seven patients groups I and II, and 31 patients in group III had at least one episode of anemia (grade 2 or above) during their chemotherapy cycles (Table 1). Overall, 293 episodes were Grade 2, 21 episodes were Grade 3, and 3 episodes were Grade 4 anemia among the 3 study groups (Tables 1, 4).
Adverse Drug Effects	Regimens	Patient Wise Incidence	Cycle Of Chemotherapy Wise(Overall) Incidence
Adverse Drug Effects		Frequency- No Of Patients (Percentage-%)	Frequency-No Of Episodes(Percentage %)	Mean Incidence/8 Cycles
Anemia(Grade 2 And Above)	REG I	27(71)	114(37.5)	3.11
	REG II	27(68)	91(28.4)	2.38
	REG III	31(67)	112(30.4)	2.7
Thrombocytopenia(Grade 2 And Above)	REG I	6(16)	5(1.6)	0.16
	REGII	5(12)	4(1.25)	0.12
	REGIII	1(2)	2(0.005)	0.04

Table 2

Distribution of different grades of anemia in the 3 study groups according to the initial 4, final 4, and overall 8 cycles of chemotherapy.
REG	GRADE ANEMIA	INITIAL 4	FINAL4	TOTAL8
AC-T	Grade1	87	70	157
	Grade2	38	69	107
	Grade3	2	3	5
	Grade4	2	0	2
AC-T + C	Grade1	113	91	204
	Grade2	24	59	83
	Grade3	3	4	7
	Grade4	0	1	1
AC-T + T	Grade1	110	104	204
	Grade2	42	61	103
	Grade3	2	7	9
	Grade4	0	0	0

The mean incidence of anemia in group I in the initial 4 cycles was 3.4+/-1.1; in the final 4 cycles, 3.7+/- 0.6; and in the overall 8 cycles, 7.1+/- 1.5. In group II, as in the initial 4 cycles: 3.5 ± 0.8; in the final 4 cycles:3.9 ± 0.4, and in the overall 8 cycles:7.4 ± 1.1. In group III, as in the initial 4 cycles: 3.3 ± 1; in the final 4 cycles: 3.7 ± 0.6; and in the overall 8 cycles:7.1 ± 1.5. (Table 2,4 & Fig. 1)

The mean incidence of all grades of anemia was comparable among the 3 study groups, with a mean incidence of 7.1 in group I, 7.4 in group II, and 7.1 in group III after 8 cycles of chemotherapy. There was no statistically significant difference in the mean incidence of anemia among the 3 study groups.

By reviewing the incidences and grades of anemia in these 124 patients, it can be clearly inferred that the incidence of anemia is greater during chemotherapy cycles. This can be attributed to the cumulative toxicity of the chemotherapy regimens to the patient's bone marrow. Figure 2 clearly shows the pattern of the decrease in Hb in the patients after each chemotherapy cycle. hemoglobin levels are presented as the mean values of hemoglobin prechemotherapy and post-chemotherapy. On analysis, there was a statistically significant difference in the prechemotherapy and post-chemotherapy hemoglobin levels, with a p-value of 0.000 for each chemotherapy cycle from cycle 1 to cycle 8. There were also significant differences in baseline hemoglobin levels and prechemotherapy 4th cycle hemoglobin levels; baseline hemoglobin levels and post-chemotherapy 4th cycle hemoglobin levels; baseline hemoglobin levels and prechemotherapy 8th cycle hemoglobin levels; and post-chemotherapy 8th cycle hemoglobin levels. The p-value of these comparisons was 0.000.

The pattern of distribution of thrombocytopenia in patients receiving three regimens of chemotherapy

Table 3

Distribution of Thrombocytopenia Grade among the 3 groups according to initial 4, final 4, and overall 8 cycles of chemotherapy
Reg	Grade THP	Initial 4	Final4	Total8
AC-T	Grade1	17	13	30
	Grade2	3	1	4
	Grade3	1	0	1
	Grade4	0	0	0
AC-T + C	Grade1	7	26	33
	Grade2	3	1	4
	Grade3	0	0	0
	Grade4	0	0	0
AC-T + T	Grade1	13	22	35
	Grade2	0	2	2
	Grade3	0	0	0
	Grade4	0	0	0

The mean incidence of thrombocytopenia in group I in the initial 4 cycles was 0.1+/- 0.5; in the final 4 cycles, 0.2+/- 0.6; and in the overall 8 cycles, 0.3+/-0.1. In group II, as in the initial 4 cycles:0.1+/-0.3; in the final 4 cycles:0.3 ± 0.6; and in the overall 8 cycles: 0.4 ± 0.7. In group III, as in the initial 4 cycles, 0 + 0; in the final 4 cycles, 0.1 ± 0.4; and in the overall 8 cycles, 0.1 ± 0.4 was found.(Fig. 3)

The mean incidence of thrombocytopenia of all grades was comparable among the 3 study groups, with 0.3 in group I,0.4 in group II, and 0.1 in group III for a total of 8 cycles of chemotherapy. There was no statistically significant difference in the mean incidence of thrombocytopenia among the 3 study groups. There was a statistically significant difference in the mean incidence of thrombocytopenia in the initial 4 cycles of chemotherapy among the 3 regimens.

The pattern of the mean platelet count according to overall patient prechemotherapy and post-chemotherapy cycles is shown in Fig. 4. The statistical analysis of the platelet count values was done using Wilcoxson signed rank test. There was a statistically significant difference between the pre-chemotherapy and post-chemotherapy platelet counts at 1–8 cycles(p value = 0.000). A comparison of the baseline platelet count before chemotherapy and after the fourth cycle of chemotherapy revealed that the post-8th cycle platelet count was significantly different, with a p-value of 0.000. Therefore, both the Adriamycin and cyclophosphamide regimens during the initial 4 cycles caused statistically significant changes in the PLT in the overall study population. In the final 4 cycles of chemotherapy, docetaxel or docetaxel + carboplatin and docetaxel + trastuzumab-based chemotherapy( i.e. docetaxel-based chemotherapy regimens) regimens caused changes in the platelet count in the overall study population.

Among the three study groups, there was a statistically significant difference in the mean platelet count only during the initial 4 cycles of chemotherapy, but there was no statistically significant difference in the final 4 cycles or overall 8 cycles of chemotherapy.

Myelosuppression is a common adverse effect associated with breast cancer chemotherapy involving anthracyclines and taxanes(4). A total of 124 breast cancer patients with an average mean age of 49 years and a mean body surface area of 1.6 m² were diagnosed with stage 1 to stage 3 disease and underwent 8 cycles of chemotherapy for a total of 992 cycles.

GRADING OF ANAEMIA, THROMBOCYTOPENIA(13):

Definition

Anemia: a disorder characterized by a reduction in the amount of hemoglobin in 100ml of blood. Symptoms of anemia may include pallor of the skin and mucous membrane, shortness of breath, palpitations of the heart, soft systolic murmurs, lethargy, and fatigue.

Thrombocytopenia: A finding based on laboratory test results indicating a decrease in the number of platelets in blood specimens.

Table 4

Grading Of Anemia, Thrombocytopenia-Common Terminology Criteria For Adverse Events- US, Department Of Health And Human Services
	Grade 0	Grade 1	Grade 2	Grade3	Grade4	Grade5
Hemoglobin	Within normal	<LLN-10 gm/dl	8.0-<10 gm/dl	< 8 gm/dl, transfusion indicated	Life-threatening complications and urgent intervention needed	Death
Platelet count	<LLN-75,000/mm³	< 75000 − 50000/mm³	< 50000 − 25000/mm³	< 25000/mm³	-	-

The incidence of thrombocytopenia was as follows: Grade 1–4: 109 (10.9%) episodes, 35 (3.5%) in Regimen I, and 37 (3.7%) in Regimen II and Regimen III. Among these, clinically relevant thrombocytopenia of grade 2 or grade 3 was identified as occurring in only 11 episodes overall, with Regimen I exhibiting 5 episodes, Regimen II exhibiting 4 episodes, and Regimen III exhibiting 2 episodes. Grade 3 thrombocytopenia with a count < 50000 cells/dl may be associated with complications and the chance of internal bleeding. Patients with Grade 3 thrombocytopenia may need platelet transfusion depending on the clinical scenario. The mean incidence was significantly greater for Regimen I. The incidence of thrombocytopenia in one study with an AC-T regimen was 1.6%, and that in another study with AC-T + Tr was 2.1%(14).

Overall 882 episodes (88.9%) of anemia (grade 1 or above) noticed in the study. Out of which 271 (27.4%) episodes in regimen I, 295(29.7%) episodes in regimen II, 316(31.8%)episodes in regimen III.

Out of which clinically relevant episodes( grade 2 and above) anemia was noticed as described. In Regimen I the total incidence of grade 2 and above grade of anemia was 114 episodes(11.49%), similarly in Regimen II and III as 91 episodes(9.1%) and 112 episodes (11.29%) respectively.

Regimens I, II, and III had 5,7,9 episodes of grade 3 anemia respectively. All these episodes are managed with blood transfusion. 2, 1 episode of grade 4 anemia occurred in regimens I and II respectively. These episodes were managed with blood transfusion and other supportive measures as may have serious life-threatening sequelae.

In a study by Jeffrey et al., the overall incidence of anemia with an AC regimen was 40%(15). In the initial 4 cycles, the incidence of anemia incidence was 424 episodes (42%), and the final 4 cycles as 469 episodes (47%). However, between the three regimens, there was no statistically significant difference in the mean incidence of anemia during the initial 4 cycles of chemotherapy, the final 4 cycles of chemotherapy or a total 8 cycles of chemotherapy.

A systematic review of early triple-negative breast cancer patients receiving platinum-based chemotherapy by Manson SRE et al reported that more hematological toxicity occurred in the platinum group than in the control group, with a relative risk ratio of 8.2 and a 95% confidence interval of 5.66–11.86 out of 18 studies; additionally, 4757 patients and thrombocytopenia patients with a relative risk of 7.59 and 95% confidence interval of 5.10 to 11.29 were included in 18 studies with 4731 patients.(16) A cross-sectional study reported by Leila Pourali et al. described the frequency of anemia induced by chemotherapy regimens in patients with breast cancer, in which the chance of developing anemia was greater in patients who received the 8-cycle AC + paclitaxel regimens than in those who received the 6 cycles of regimens or other chemotherapy regimens.(17)

There was no statistically significant difference in the incidence of anemia among the 3 groups in the initial 4 chemotherapy cycles, final 4 chemotherapy cycles, or overall, 8 cycles of chemotherapy. There was a statistically significant difference in the mean incidence of thrombocytopenia during the initial 4 cycles of chemotherapy among the 3 regimens. However, after 8 cycles of chemotherapy, there was no statistically significant difference in the mean incidence of thrombocytopenia. There is a clear-cut pattern of decrease in Hb levels towards later cycles of chemotherapy due to the cumulative toxicity of chemotherapy regimens to the bone marrow.

AC-T (adriamycin and cyclophosphamide followed by docetaxel)
AC-T+C/Ca (adriamycin and cyclophosphamide followed by docetaxel and carboplatin)
AC-T+Tr/T(adriamycin and cyclophosphamide followed by docetaxel and trastuzumab)
HB PR RE1(mean value of hemoglobin pre-chemotherapy in Regimen 1 in 8 cycles)
HB PO RE1(mean value of hemoglobin post-chemotherapy in Regimen 1 in 8 cycles)
HB PR RE2(mean value of hemoglobin prechemotherapy in regimen 2 in 8 cycles)
HB PO RE2(mean value of hemoglobin post-chemotherapy in Regimen 2 in 8 cycles)
HB PR RE3(mean value of hemoglobin prechemotherapy in Regimen 3 in 8 cycles)
HB P0 RE2(mean value of hemoglobin post-chemotherapy in Regimen 3 in 8 cycles)
PLT PR RE1(mean value of platelet count prechemotherapy in Regimen 1 in 8 cycles)
PLT PO RE1(mean platelet count post-chemotherapy in Regimen 1 in 8 cycles)
PLT PRRE2(mean platelet count during prechemotherapy in Regimen 2 in 8 cycles)
PLT PORE2(mean platelet count post- chemotherapy in Regimen 2 in 8 cycles)
PLT PR RE3(mean value of platelet count prechemotherapy in Regimen 3 in 8 cycles)
PLT PR RE3(mean platelet count post-chemotherapy in Regimen 3 in 8 cycles)
TNBC- Triple-negative breast cancer

Funding: No funding sources

Conflict of interest: There are no conflicts of interest among the investigators.

Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethical approval: The study was approved by the institutional ethics committee of the Government Medical College Kozhikode, and the patient was enrolled in the study after providing written informed consent.

Authors' contributions: Prospective, open-label study patient enrollment, consent, and data documentation were provided by AS. The manuscript was prepared and written by AS, SM, and AT. Manuscript reviewed by AS, SM, AT, and AM. The final manuscript was approved by AS, SM, and AT.

Acknowledgments: I would like to acknowledge Professor. Dr. Jeeja M Former Professor and head of the Department of Pharmacology, Government Medical College Idukki, presently Professor and Head of the Pharmacology department, MES Medical College Perinthalmanna, Dr. Jayakrishnan T Former Professor of Community Medicine Department Government Medical College Kozhikode To support the writing and suggestions for invaluable suggestions and unwavering support, which have greatly enriched the quality and depth of our study.We extend our heartfelt appreciation to Dr.Anoop Pratheesh P, Surgeon in Government Health Services, Kerala, and Dr. G. Krishnakumar, Physician and Intensivist at Dr. Govindans Hospital Thiruvananthapuram. Dr. Sneha Ambwani Professor and Head of the Pharmacology Department, AIIMS, Jodhpur, Dr. Shanthanu Munshi Professor and Head of Clinical Pharmacology School of Tropical Medicine Calcutta for constant support in preparing and publishing the manuscript.

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The authors declare no competing interests.

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Incidence of Anaemia and Thrombocytopenia Following Breast Cancer Chemotherapeutic Regimens AC-T, AC-T+ Ca, and AC-T+Tr IN in a Tertiary Care Center

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Abstract

Figures

INTRODUCTION

METHODS

It is calculated by the formula

Dosage and administration

AC-docetaxel regimen

AC-docetaxel and carboplatin regimen

AC-docetaxel and trastuzumab regimen

Dosage of Peg filgrastim/Filgrastim for neutropenia associated with myelosuppressive chemotherapy:

OUTCOME ASSESSMENT

RESULTS

Baseline demographic features:

Incidence of anemia in patients receiving different chemotherapy regimens:

The pattern of distribution of thrombocytopenia in patients receiving three regimens of chemotherapy

DISCUSSION

GRADING OF ANAEMIA, THROMBOCYTOPENIA(13):

CONCLUSION

Abbreviations

Declarations

References

Additional Declarations

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