A Phase I/II Trial of DA3030 in Chemotherapy Induced Neutropenia.
- Author:
Hyun Cheol CHUNG
1
;
Sun Young RHA
;
Soo Jung GONG
;
Hwa Young LEE
;
Hei Cheol CHUNG
;
Churl Woo AHN
;
Wook Jin CHUNG
;
Rutha LEE
;
Bo Young CHOUNG
;
Seung Keun LEE
;
Yoon Soo CHANG
;
Nae Choon YOO
;
Joo Hang KIM
;
Jae Kyung ROH
;
Jin Sik MIN
;
Byung Soo KIM
;
Bum Soo PARK
;
Mi Young BAHNG
Author Information
1. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
- Publication Type:Clinical Trial ; Original Article
- Keywords:
Chemotherapy-induced leukopenia DA-3030;
Efficacy;
100microgram/m2
- MeSH:
Anti-Bacterial Agents;
Drug Therapy*;
Half-Life;
Humans;
Leukopenia;
Myalgia;
Neutropenia*;
Neutrophils
- From:Journal of the Korean Cancer Association
1997;29(5):886-898
- CountryRepublic of Korea
- Language:Korean
-
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 microgram/m2/day (step I), 100 microgram/m2/day (step II), 150 microgram/m2/day (step III), 200microgram/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 100microgram/m2 is an appropriate dosage for the phase III clinical trial.
