David Praveenkumar, D (2011) A Study on Antibacterial Prophylaxis after Chemotherapy for Breast Carcinoma patients. Masters thesis, Cancer Institute (WIA), Chennai.
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Abstract
INTRODUCTION: With the advent of cytotoxic therapy for cancer especially the intensified dose regimens used in haematological cancer and solid tumors, occurrence of febrile neutropenia poses a major problem in treating this patient population. Though fever and infection as a consequence of neutropenia, in cancer patients were first described about 100 years ago still bacterial infections are life threatening complications in patients with severe, persistent neutropenia. Without preventive measures, 48% to 60% of febrile neutropenic patients have an infection, while 16% to 20% of profoundly neutropenic patients (neutrophil counts <0.1 x 109 cells/L) develop bacteraemia. Neutropenia leads to increased hospitalisation, increased costs and loss of quality of life. Most dreadful complication of febrile neutropenia is mortality which ranges from 2 to 21% in various studies. To prevent chemotherapy-related FN, prophylactic antibiotics and granulocyte colony-stimulating factor (G-CSF) have been applied successfully. Earlier Studies evaluating prophylaxis with trimethoprim–sulfamethoxazole (TMP-SMZ) demonstrated a reduced infection rate for patients treated with TMP-SMZ when compared with placebo or no treatment. However with the decreasing efficacy of TMP-SMZ in modern times fluroquinolones have emerged as a good alternative for prophylaxis in febrile neutropenia. When quinolones are used for prevention of infection in neutropenic patients, the rate of Gram-negative bacteraemia is reduced to 1–2%. The advantages of using fluroquinolones are: they are orally absorbable, have broad antimicrobial spectrum and also have some activity against gram positive organisms and it is cost –effective. The main problem with chemoprophylaxis is the emergence of resistance especially to Escherichia coli; however, since the antibiotics used for chemoprophylaxis in cancer patients are widely used in the community, it is unlikely that their use in neutropenic patients will significantly aggravate the overall situation. Many drugs in the fluroquinolone group such has ciprofloxacin, moxifloxacin and levofloxacin has been tried as prophylaxis in febrile neutropenia in various studies across the world. Gatifloxacin has not been tried in vivo in the chemoprophylaxis of febrile neutropenia. Also there is a paucity of studies related to the prophylaxis in febrile neutropenia in our country where the disease burden is substantial when compared to the western countries. In this background this study is attempted to assess the clinical evidence supporting the efficacy of antibiotic prophylaxis with fluoroquinolones in neutropenic cancer patients. AIM OF THE STUDY: To assess the clinical evidence and impact supporting the efficacy of antibiotic prophylaxis with fluoroquinolones in neutropenic breast carcinoma patients. METHODOLOGY: 1. 188 breast carcinoma patients were randomly assigned to treatment or observation group each consisting of 94 patients after informed consent. Study period was between October 2009 – November 2010. 2. Patients were stratified according to age (less than 50 years, 50 years or older), whether they receive concurrent chemoradiotherapy or not and metastatic or non-metastatic disease. 3. Treatment group patients received Gatifloxacin 400 mg OD from day 6 to day 14 of each chemotherapy cycle. 4. When febrile neutropenia occurred , no chemotherapy dose compromise in next cycle was allowed except in patients complicated by life threatening infections. 5. Definition of Febrile neutropenia- A single oral temperature of greater than 38.3°C (101°F) or 38.0°C or greater (100.4°F) for over 1 hour with ANC less than 500 mcL or less than 1,000 mcL with predicted rapid decline. 6. All febrile neutropenic patients were admitted in the hospital and started on broad spectrum antibiotics according to hospital protocol. 7. Decision on oral or IV antibiotic was decided by the treating physician based on age, PS, and clinical picture. It was continued till all signs of infection and fever disappeared. 8. For all admitted patients chest Xray and blood culture was done. Total count \ Absolute Neutrophil count was done daily till the count is non neutropenic. 9. Admitted patients were discharged from the hospital if afebrile for 2 days , no active infection or ANC > 500. 10. Decision on growth factors were taken by the discretion of treating phycisian on the basis of age, comorbids, severity of infection etc. 11. Severe infection is defined as sepsis related syndrome , pneumonia, hypotension or death. PATIENT SELECTION: Inclusion Criteria: 1. Age > 20 years & < 70 years. 2. PS – 0,1. 3. Histologically proven invasive breast carcinoma. 4. Chemotherapy regimens. Breast carcinoma – FEC (5-Flurouracil, Epirubicin,Cyclophosphamide), TE (Taxol, Epirubicin) with or with out concurrent radiotherapy (40 gy). Exclusion Criteria: 1. Poor Performance Status (2, 3, 4). 2. Compromised renal, hepatic, cardiac function. 3. Pancytopenia due to bone marrow involvement. 4. Active infection / current antibacterial therapy. 5. Cerebral metastases. 6. Previous malignancy. 7. H/O epilepsy, uncontrolled Diabetis Mellitus. 8. Hemoglobin < 10 gm \ dl,. Total count < 4000. 9. H/O adverse reactions to Quinolones. 10. Previous chemotherapy / Radiotherapy. 11. Pregnancy and breast feeding. All patients had hemogram, renal function test (blood urea, serum creatinine), liver function test (serum bilirubin, SGOT, SGPT, ALP), chest Xray, ECG, ECHO, US abdomen. SUMMARY AND CONCLUSION: This study is an attempt to assess the clinical evidence supporting the efficacy of antibiotic prophylaxis with fluoroquinolones in neutropenic cancer patients. 188 breast carcinoma patients were randomly assigned to treatment or observation group each consisting of 94 patients. Treatment group patients received Gatifloxacin 400 mg OD from day 6 to day 14 of each chemotherapy cycle. Patients who developed febrile neutropenia were admitted in the hospital and oral or IV antibiotics were administered based on age, PS and clinical picture of patients. Primary end points of the study were the number of febrile episodes, documented infection, culture positive infection, infection related mortality while the secondary end points of the study include number of febrile episodes in first and then subsequent cycles, days of hospitalisation , ICU admissions, requirement of intravenous antibiotics, isolation of organisms, whether antibiotic prophylaxis helpful in elderly or patients with comorbids. The incidence of febrile neutropenia in first cycle is considerably less in antibiotic group. The protective effect of antibiotic is 3 times more effective in first cycle and it is statistically significant where it is only 2 times in rest of the cycles which is not statistically significant. The incidence of hospital admission in our study was 5.3% and 15.9% in antibiotic and placebo groups respectively in first cycle where as it was 2.76% and 5.53% in subsequent cycles .In our study median days of hospital admission was similar in both arms ie., 5 days . In this study there was almost 50% reduction of hospitalisation with prophylactic antibiotics across all cycles. Clinically documented infections was observed in 9 out of 18 patients (50%) and 15 out of 41 patients (36.5%) in antibiotic and placebo groups respectively.One patient had life threatening diarrhoea and three more patients had pneumonia requiring ICU admission in placebo group where as only one patient in antibiotic group had admission in ICU for pneumonia. So ICU admissions are reduced considerably in antibiotic group. Conclusions drawn from this study include: 1. Incidence of febrile neutropenia is decreased in patients who received gatifloxacin and this effect was seen considerably more in the first cycle of chemotherapy than the subsequent cycles. 2. Incidence of hospitalization due to febrile neutropenia was also less in patients receiving antibiotic prophylaxis .However median duration of hospitalization of patients remained the same irrespective of antibiotic prophylaxis or not. 3. Antibiotic prophylaxis also reduced the need of intravenous antibiotics in patients with febrile neutropenia. 4. Clinically and microbiologically documented infection was not decreased with the use of antibiotic prophylaxis. 5. Antibiotic prophylaxis did not exert additional positive effect in patients with comorbid condition and in patients with metastatic disease.
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | Antibacterial Prophylaxis ; Chemotherapy ; Breast Carcinoma ; Patients. |
| Subjects: | MEDICAL > Medical Oncology |
| Depositing User: | Subramani R |
| Date Deposited: | 19 Aug 2017 03:37 |
| Last Modified: | 09 May 2018 17:03 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/2037 |
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