진행성 악성종양에서 항암약물요법에 의한 호중구 감소증에 대한 DA-3030(재조합 과립구 콜로니 자극인자: rhG-CSF)의 안전성 및 효과를 평가하기 위한 제 Ⅰ/Ⅱ상 임상시험
A Phase Ⅰ/Ⅱ Trial of DA3030 in Chemotherapy Induced Neutropenia
대한암학회지 1997년 29권 5호 p.886 ~ 898
소속 상세정보
정현철/Hyun Cheol Chung
KMID : 0360319970290050886
Abstract
결론
DA-3030의 Ⅰ/Ⅱ상 임상연구 결과 투여 4단계까지 용량 감소가 필요라는 부작용은 관찰
되지 않아 200 μg/m2까지도 투여가 가능하다고 사료된다. 그러나 혈액소견
에 미치는 영향, 투여효과, 부작용, 감염빈도, 항생제 사용기간 등을 고려하여 임상유효성을
평가한 결과, 제 3상 임상시험에 사용될 수 있는 권장량은 100 μg/m2가 적
절하리라 사료되었다.
#초록#
Purpose : We planned to evaluate the toxicity and efficacy of DA-3030 to determine
the recommended dose for phase Ⅲ clinical trial based on the biologically active doses
from phase Ⅰ/Ⅱ clinical trial.
Materials and Methods : Open non-randomized phase Ⅰ/Ⅱ study was carried out in
64 cancer patients with chemotheray-induced myelosuppression. After 1 cycle of control
period (chemotherapy without DA-3030), DA-3030 was started 24 hours after the second
cycle of chemotherapy to 4 groups of patients with the doses of 50 μ
g/m2/day(step Ⅰ), 100 μg/m2/day(step Ⅱ), 150 μ
g/m2/day(step Ⅲ), 200μg/m2/day(step Ⅳ) by once-a-day
subcutaneous administration for 10 days.
Results : Of the 64 enrolled patients, 46 patients were evaluable. Tmax reached after
2 hours of injection in step Ⅰ and 4 hours in step Ⅱ-Ⅳ. Terminal half life was 1.8
hours in step Ⅰ and 3.2 hours in step Ⅱ, 3.3 hours in step Ⅲ, 3.0 hours in step Ⅳ.
Area under the curve (AUC) and AUMC increased dose dependently from step Ⅰ
through step Ⅳ. Total clearance rate decreased in a dose dependent manner but the
volume of distribution showed no differences between the steps. The mean nadir count
of total WBC and neutrophil increased in all 4 steps of DA-3030 administration. Also
the duration of leukopenia, equal to or less than 2,000/uL or neutropenia and the
recovery time of WBC or neutrophil from nadir decreased with DA-3030 administration
in all 4 steps. But no difference of DA-3030 effect was found among 4 steps. When we
compared the clinical efficacy of DA-3030 with total WBC and neutrophil criteria, it was
58.3% and 58.3% in step Ⅰ, 90.0% and 80.0% in step Ⅱ, 91.7% and 91.7% in step Ⅲ,
75.0% and 70.0% in step Ⅳ. Although the duration of antibiotics administration showed
no difference between control and DA-3030 administration period in step Ⅰ, it decreased
with DA-3030 administration in step Ⅱ-Ⅳ Infection was found only in step Ⅰ.
Life-threatening side effect was not found in all steps. Only mild myalgia was found
without any dose relationship.
Conclusion : When we considered the efficacy, toxicity and pharmacokinetic
parameters, we suggest that 100μg/m2 is an appropriate dosage for the
phase Ⅲ clinical trial.
키워드
Chemotherapy-induced leukopenia DA-3030; Efficacy; 100μg/m2;
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