A Phase I/II Trial of DA3030 in Chemotherapy Induced Neutropenia

Chung, Hyun Cheol; Rha, Sun Young; Gong, Soo Jung; Lee, Hwa Young; Chung, Hei Cheol; Ahn, Churl Woo; Chung, Wook Jin; Lee, Rutha; Choung, Bo Young; Lee, Seung Keun; Chang, Yoon Soo; Yoo, Nae Choon; Kim, Joo Hang; Roh, Jae Kyung; Min, Jin Sik; Kim, Byung Soo; Park, Bum Soo; Bahng, Mi Young

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.