유방암 환자에서 TAC 항암치료에 의한 호중구감소증에 대한 트리페그필그라스팀의 예방효과 평가
- Issued Date
- Neutropenia, an adverse event of cytotoxic chemotherapeutic agent, is one of the major concerns in breast cancer patients. As a therapeutic agent for the neutropenia, recombinant human granulocyte-colony stimulating factor (G-CSF, filgrastim) is developed. Recently, pegylated G-CSF (pegfilgrastim, tripegfilgrastim) used to prevent neutropenia induced by chemotherapeutic agent has been introduced for thepurpose of longer duration of action. Tripegfilgastim, a filgrastim with branched pegylation, is developed for the better bioavailability with less aggregation and depegylation than those of pegylated filgrastim.
In this study, breast cancer patients with TAC (docetaxel/doxorubicin/cyclophosphamide) regimen were collected. We analyzed prophylactic tripegfilgrastim (PT) group, prophylactic pegfilgrastim (PP) group and non-prophylactic G-CSF (non-PG) group with incidence of neutropenia, febrile neutropenia, events of absolute neutrophil count (ANC) below 50% of baseline, cycles of dose reduction of chemotherapeutic agent, hospitalization duration, risk factors associated with neutropenia and febrile neutropenia.
Among the total 97 breast cancer patients with TAC regimen, prophylactic G-CSFs were treated in 31 patients (tripegfilgrastim) and 33 patients (pegfilgrastim). Non-PG group was 33 patients. Incidence of neutropenia (PT 22.58%, PT 39.39% non-PG 81.82% p<0.001), febrile neutropenia (PT 6.45%, PP 15.15% non-PG 42.42% p=0.001), events of ANC below 50% of baseline (PT 19.35%, PP 48.48% non-PG 90.91% p<0.001) hospitalization duration (PT 7.35±2.09 days, PT 10.82±11.68 non-PG 13.27±8.77 p=0.002) of prophylactic group (PT, PP) are significantly lower than those of non-PG group. The risk factor associated with neutropenia was use of Tripegfilgrastim (HR 0.065 CI 0.02-0.22) and Pegfilgrastim (HR 0.144 CI 0.05-0.45)(p<0.001). And incidence of febrile neutropenia was lower in PT group (HR 0.094 CI 0.02-0.46) and PP group (HR 0.242 CI 0.07-0.78) than non-PG group (p=0.003).
In conclusion, use of prophylactic G-CSF is beneficial to the breast cancer patients treated with TAC regimen. The study showed better outcome in PT groups than PP groups.| 호중구감소증은 항암치료를 받는 환자에게 있어 흔히 일어나는 세포화학독성 항암제의 주요 부작용으로써 항암요법을 지연시키거나, 변경하거나, 용량을 감소하게 하거나, 중단시킴으로써 환자의 치료에 부정적 영향을 줄 수 있다. 호중구감소증을 치료하기 위해서 재조합 메티오닐 인 과립구 콜로니자극인자(recombinant methionyl human granulocyte colony stimulating factor, r-metHuG-CSF)가 개발되었다. 최근에는 항암제로 인한 호중구감소증을 예방하는 목적으로 G-CSF를 pegylation하여 약효를 연장시킨 2세대 G-CSF (pegfilgrastim, tripegfilgrastim)가 개발되었다. 1세대 G-CSF인 Filgrastim에 branched PEG를 결합시킨 Tripegfilgrastim은 기존의 Pegylated filgrastim (Pegfilgrastim)보다 aggregation과 depegylation을 줄이기 위해 개발되었다.
본 연구에서는 호중구감소증 고위험 항암화학요법인 유방암의 adjuvant TAC 항암화학요법을 받은 환자를 대상으로 예방 목적으로 2세대 G-CSF를 사용한 군(tripegfilgrastim, pegfilgrastim), 그리고 예방적인 G-CSF를 사용하지 않은 군에서 호중구감소증, 열성 호중구감소증의 발생빈도를 비교하고 그에 영향을 끼치는 요인 및 발생위험요인 등을 분석하였다. 그리고 2세대 G-CSF 중 pegylation 형태가 다른 Tripegfilgrastim과 Pegfilgrastim에서 호중구감소증 및 열성 호중구감소증 발생률과 관련된 요인들을 비교 분석하였다. 이를 통하여 2세대 G-CSF의 호중구감소증 예방 효과와 2세대 G-CSF 중 Tripegfilgrastim과 Pegfilgrastim의 약효를 비교 분석하였다.
adjuvant TAC 치료를 받는 총 97명의 환자 중 예방적 목적으로 G-CSF를 사용한 환자는 Tripegfilgrastim군(PT군) 31명, Pegfilgrastim군(PP군) 33명, 예방적인 G-CSF를 사용하지 않은 환자(Non-PG군) 33명이었다. 호중구감소증 발생률(PT 22.58%, PT 39.39% non-PG 81.82% p<0.001), 열성 호중구감소증 발생률(PT 6.45%, PP 15.15% non-PG 42.42% p=0.001), 항암화학요법 후 측정한 ANC가 기저 ANC의 50% 이하로 감소한 환자수 (PT 19.35%, PP 48.48% non-PG 90.91% p<0.001), 평균재원일(PT 7.35±2.09 days, PT 10.82±11.68 non-PG 13.27±8.77 p=0.002)에서 유의한 차이를 보였다. 호중구감소증의 가장 큰 위험인자는 Tripegfilgrastim과(HR 0.065 CI 0.02-0.22) Pegfilgrastim의(HR 0.144 CI 0.05-0.45)(p<0.001) 사용 유무였다. 열성호중구 감소증 발생률은 PT군과(HR 0.094 CI 0.02-0.46) PP군(HR 0.242 CI 0.07-0.78)에서 Non-PG group군에 비해 낮게 나타났다(p=0.003).
예방적 2세대 G-CSF 사용군(PG군)은 호중구감소증 및 열성 호중구감소증의 예방뿐 아니라 재원일수의 감소 등 치료의 여러 측면에서 2세대 G-CSF를 사용하지 않은 군(Non-PG군)에 비해 통계적으로 양호한 결과를 보였다. 호중구감소증 및 열성 호중구감소증의 발생 유무가 전체 항암화학요법의 성패와도 연관 있는 것을 고려해보았을 때 약가와 효용성을 잘 고려하여 보다 적극적으로 예방적 G-CSF의 사용이 권장되어야 할 것이다.
- Alternative Title
- Analysis of preventive effect of tripegfilgrastim on the TAC chemotherapy induced neutropenia in breast cancer patients.
- Alternative Author(s)
- Miran Lee
- 임상약학대학원 임상약학과
- Awarded Date
- Table Of Contents
- 목 차
I. 서 론 ······························································ 1
A. 연구 배경···························································· 1
B. 연구 목적···························································· 3
Ⅱ. 연구 대상 및 방법··············································· 4
A. 연구 대상···························································· 4
B. 의학연구윤리심의위원회(IRB) 승인 ························· 4
C. 자료 수집······························································5
D. 결과 평가······························································5
E. 용어 정의······························································6
F. 통계 분석······························································7
Ⅲ. 연구 결과·······························································8
A. 연구 대상의 분포 및 특징·······································8
B. 세 군의 결과 비교················································11
1. 세 군의 ANC 비교·················································11
2. 전체 환자에서 호중구감소증 및 관계된 인자의 비교······12
3. 전체 주기에서 호중구감소증 및 관계된 인자의 비교······14
4. 호중구감소증 환자들의 분포 및 특징··························16
5. 기저 ANC 대비 50% 이하 감소 환자들의 분포 및 특징···18
6. 예방적 G-CSF 사용군의 호중구감소증 관련 인자 비교····20
7. 호중구감소증 및 열성 호중구감소증의 위험인자············22
8. 약가 및 기타사항 비교 ··········································24
Ⅳ. 고 찰····································································26
V. 결 론····························································30
- 이미란. (2017). 유방암 환자에서 TAC 항암치료에 의한 호중구감소증에 대한 트리페그필그라스팀의 예방효과 평가.
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