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Title   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 )
Publicationinfo   1997 Jan; 029(05): 886-899.
Key_word   Chemotherapy-induced leukopenia DA-3030, Efficacy, 100 ug/m2
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Abstract   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 ug/m2/day(step I), 100 ug/m2/day(step II), 150 ug/m2/day(step III), 200ug/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 differece 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 100ug/m2 is an appropriate dosage for the phase III clinical trial.
저 자   정현철(Hyun Chul Chung),라선영(Seon Young Rah),공수정(Soo Jung Kong),이화영(Hwa Young Lee),정희철(Hei Cheol Chung),안철우(Chul Woo Ahn),정욱진(Wook Jin Chung),이루다(Rutha Lee),정보영(Bo Young Jung),이승근(Seung Geun Lee),장윤수(Yoon Soo Chang),유내춘(Nae Choon Yoo),김주항(Joo Hang Kim),노재경(Ja