유방암에서 Cyclophosphamide, Thiotepa, Carboplatin의 고용량 복합 항암 화학요법 후 자가 말초 혈액 조혈 모세포 이식술
High Dose Cyclophosphamide, Thiotepa, and Carboplatin followed by tautologous Peripheral Stem Cell Rescue in Patients with Responsive Metastatic or High-Risk Primary Breast Cancer
대한암학회지 1998년 30권 1호 p.100 ~ 105
소속 상세정보
조세행
김상위/민영주/최성준/김정균/김태원/최종수/장대영/이제환
KMID : 0360319980300010100
Abstract
서론
전이된 유방암 환자의 중앙 생존 기간은 2년 미만이며, 기존의 복합 항암 화학 요법을 시
행할 경우 반응률은 50∼70%, 완전 반응률은 20% 정도로 보고되고 있다. 그러나 화학 요법
반응군의 무병 생존 기간은 3∼5개월 내외로 짧으며, 복합 화학 요법에 의한 총 생존 기간
의 연장 효과는 크지 않다. 또한 수술 당시 유방 종괴의 크기가 5 cm이상이거나 전이된 액
와 림프절의 갯수가 10개 이상인 고위험군 환자의 5년 무병 생존율은 기존의 수술 후 보조
항암 화학 요법에 의해서도 38∼50%에 불과하다. 따라서 전이된 유방암 환자의 생존율 향
상 및 수술 후 재발을 예방하기 위하여 새로운 복합 항암 화학 요법의 개발이 절실하다. 유
방암은 비교적 항암제에 민감한 종양으로 알려져 있고 종양의 반응률은 투여한 항암제의 용
량과 비례하는 것으로 알려져다. 고용량의 항암제를 투여할수록 종양의 반응율은 향상되나
골수 억압 등의 부작용으로 임상 적용이 어렵다. 그러나 최근 고용량 항암제투여 후 자가
골수 또는 말초 혈액 조혈 모세포를 이식함으로써 빠른 골수 기능 회복을 도모하고자 하는
시도가 활발히 이루어지고 있다. 연구자 등은 1994년 9월부터 1997년 3월까지 11예의 여자
유방암 환자를 대상으로 cyclophosphamide, thiotepa, carboplatin (CTCb)의 고용량 복합항
암 화학 요법 후 자가 말초 혈액 조혈 모세포 이식을 시행하여 제 2상 임상 연구를 진향하
였다.
Purpose : Positive correlation between dosage of antineoplastic agents and tumor
response is well demonstrated in advanced breast cancer. But severe bone marrow
depression limit the clinical application of high dose chemotherapy. Autologous peripheral
blood stem cell transplantation(PBSCT) after high dose chemotherapy(HDC) was
introduced to promote rapid bone marrow recovery. This study was designed to
establish the feasibility of combining high dose cyclophosphamide, thiotepa, and
carboplatin chemotherapy followed by stem cell rescue in patients with responsive
metastatic or high risk primary breast cancer.
Materials and Method : Eligibility criteria included the presence of high risk primary
breast cancer(10 or more involved axillary lymph node, n=4), recurrent disease after
curative resection(n=6) or stage IV disease at the time of diagnosis(n= 1). The
responses of recurrent disease to initial chemotherapy were 4 complete responses and 1
partial responses. One recurrent case with solitary pulmonary metastasis underwent
metastasectomy and got chemotherapy after operation. Colony stimulating factor was
administered to mobilize stem cells from bone marrow to peripheral blood. 1%e stem cell
collection was performed 4∼10 times(median 4) and the number of collected stem cell
was 1.95∼7.34 H 108/kg(median 4.87 H 108/kg). High dose
chemotherapy with CTCb (cyclopho-sphamide 1,500 ㎎/m2/day, thiotepa
125 ㎎/m2/day, carboplatin 200 ㎎/m2/ day) was performed
from day-7 to day -4 and peripheral stem cell infusion was performed on day 0 as
planned.
Result : Eleven patients were enrolled in this study Their median age was 39 years
old. The median time for bone marrow recovery was 11 days for neutrophil(>
500/mm3) and 28 days for platelet(> 50,000/mm3). Packed red
blood cell and platelet transfusion were performed in 11 patients. The group whose
infused mononuclear cell count was less than 4.0×108/㎏(n=9) needed
longer time for bone marrow recovery than those(n=2) who had more than 4.0×
108/㎏(20 vs 13 day, p < 0.05). For non-hematologic toxicity, none have
experienced toxicity more than grade Ⅲ. There were 2 recurrences of 4 cases with high
risk breast cancer at the 22 th, and 25 th month but they are still alive at the 28 th,
and 29 th month each. The other 2 cases are alive without recurrences at the 18 th, and
20 th months each. In the recurrent disease group, one case who showed partial
response to initial chemotherapy recurred at the 4 th month and died at the 13 th month
after PBSCT. The other 5 cases are alive without recurrence at the 1st, 3 rd, 3 rd, 5 th,
and 31 th month each. One case with stage Ⅳ disease(bone m metastasis) is alive
without evidence of progression at the 3 rd month.
Conclusion : High dose chemotherapy with PBSCT can be performed safely. Long
term survival of patients with advanced breast cancer would be possible by PBSCT
after HDC. Further clinical trials based on larger patient population is required to
evaluate clinical efficacy of PBSCT after HDC in high risk and recurrent breast cancer.
키워드
Peripheral stem cell transplantation; Breast cancer; High dose chemotherapy;
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