Efficacy, safety, and pharmacokinetics of subcutaneous azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes

Wen Chien Chou, Su Peng Yeh, Liang Tsai Hsiao, Sheng Fung Lin, Yeu Chin Chen, Tsai-Yun Chen, Eric Laille, Anoula Galettis, Qian Dong, Steve Songer, C. L. Beach

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Abstract

Aim: Clinical and pharmacokinetic effects of azacitidine in higher-risk myelodysplastic syndromes were established in mainly Caucasian populations. Because of inter-ethnic genotype variability of drug-metabolizing enzymes, it is important to evaluate azacitidine in populations expected to use the drug. Methods: In this single-arm study, Taiwanese patients with higher-risk myelodysplastic syndromes received azacitidine 75 mg/m2/day for 7 days/28-day cycle for up to six cycles. Response-evaluable patients had baseline and cycle 6 marrow assessments. Clinical outcomes are compared descriptively with those from a phase 3 study comprising mainly Caucasian patients (N = 179). Pharmacokinetics in a subgroup of Taiwanese patients are descriptively compared with a historical control of North American patients (N = 45). Results: Median age of Taiwanese patients (N = 44) was 64 years (range 36–90), and 46% had poor cytogenetics. Median number of azacitidine cycles was six (1–6). No response-evaluable patient (n = 33) achieved complete or partial remission; however, 22 patients (50%) achieved hematologic improvement, 12 of 32 patients attained RBC transfusion independence and 7 of 18 attained platelet transfusion independence. Most common grade 3–4 treatment-emergent adverse events were neutropenia (52%) and leukopenia (39%). Pharmacokinetic profiles were similar for Taiwanese (N = 12) and North American (N = 45) patients. Maximum plasma concentration was higher in Taiwanese patients; however, mean azacitidine exposure was within the range for North American patients. Conclusion: These data confirm the safety and efficacy of azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes. Clinical outcomes were generally comparable with those for Caucasian patients. No meaningful differences in azacitidine pharmacokinetics were observed for Taiwanese patients, and no initial dose adjustment is necessary.

Original languageEnglish
Pages (from-to)e430-e439
JournalAsia-Pacific Journal of Clinical Oncology
Volume13
Issue number5
DOIs
Publication statusPublished - 2017 Oct 1

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Azacitidine
Myelodysplastic Syndromes
Pharmacokinetics
Safety
Platelet Transfusion
Leukopenia
Neutropenia

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Chou, Wen Chien ; Yeh, Su Peng ; Hsiao, Liang Tsai ; Lin, Sheng Fung ; Chen, Yeu Chin ; Chen, Tsai-Yun ; Laille, Eric ; Galettis, Anoula ; Dong, Qian ; Songer, Steve ; Beach, C. L. / Efficacy, safety, and pharmacokinetics of subcutaneous azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes. In: Asia-Pacific Journal of Clinical Oncology. 2017 ; Vol. 13, No. 5. pp. e430-e439.
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title = "Efficacy, safety, and pharmacokinetics of subcutaneous azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes",
abstract = "Aim: Clinical and pharmacokinetic effects of azacitidine in higher-risk myelodysplastic syndromes were established in mainly Caucasian populations. Because of inter-ethnic genotype variability of drug-metabolizing enzymes, it is important to evaluate azacitidine in populations expected to use the drug. Methods: In this single-arm study, Taiwanese patients with higher-risk myelodysplastic syndromes received azacitidine 75 mg/m2/day for 7 days/28-day cycle for up to six cycles. Response-evaluable patients had baseline and cycle 6 marrow assessments. Clinical outcomes are compared descriptively with those from a phase 3 study comprising mainly Caucasian patients (N = 179). Pharmacokinetics in a subgroup of Taiwanese patients are descriptively compared with a historical control of North American patients (N = 45). Results: Median age of Taiwanese patients (N = 44) was 64 years (range 36–90), and 46{\%} had poor cytogenetics. Median number of azacitidine cycles was six (1–6). No response-evaluable patient (n = 33) achieved complete or partial remission; however, 22 patients (50{\%}) achieved hematologic improvement, 12 of 32 patients attained RBC transfusion independence and 7 of 18 attained platelet transfusion independence. Most common grade 3–4 treatment-emergent adverse events were neutropenia (52{\%}) and leukopenia (39{\%}). Pharmacokinetic profiles were similar for Taiwanese (N = 12) and North American (N = 45) patients. Maximum plasma concentration was higher in Taiwanese patients; however, mean azacitidine exposure was within the range for North American patients. Conclusion: These data confirm the safety and efficacy of azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes. Clinical outcomes were generally comparable with those for Caucasian patients. No meaningful differences in azacitidine pharmacokinetics were observed for Taiwanese patients, and no initial dose adjustment is necessary.",
author = "Chou, {Wen Chien} and Yeh, {Su Peng} and Hsiao, {Liang Tsai} and Lin, {Sheng Fung} and Chen, {Yeu Chin} and Tsai-Yun Chen and Eric Laille and Anoula Galettis and Qian Dong and Steve Songer and Beach, {C. L.}",
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Chou, WC, Yeh, SP, Hsiao, LT, Lin, SF, Chen, YC, Chen, T-Y, Laille, E, Galettis, A, Dong, Q, Songer, S & Beach, CL 2017, 'Efficacy, safety, and pharmacokinetics of subcutaneous azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes', Asia-Pacific Journal of Clinical Oncology, vol. 13, no. 5, pp. e430-e439. https://doi.org/10.1111/ajco.12659

Efficacy, safety, and pharmacokinetics of subcutaneous azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes. / Chou, Wen Chien; Yeh, Su Peng; Hsiao, Liang Tsai; Lin, Sheng Fung; Chen, Yeu Chin; Chen, Tsai-Yun; Laille, Eric; Galettis, Anoula; Dong, Qian; Songer, Steve; Beach, C. L.

In: Asia-Pacific Journal of Clinical Oncology, Vol. 13, No. 5, 01.10.2017, p. e430-e439.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy, safety, and pharmacokinetics of subcutaneous azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes

AU - Chou, Wen Chien

AU - Yeh, Su Peng

AU - Hsiao, Liang Tsai

AU - Lin, Sheng Fung

AU - Chen, Yeu Chin

AU - Chen, Tsai-Yun

AU - Laille, Eric

AU - Galettis, Anoula

AU - Dong, Qian

AU - Songer, Steve

AU - Beach, C. L.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Aim: Clinical and pharmacokinetic effects of azacitidine in higher-risk myelodysplastic syndromes were established in mainly Caucasian populations. Because of inter-ethnic genotype variability of drug-metabolizing enzymes, it is important to evaluate azacitidine in populations expected to use the drug. Methods: In this single-arm study, Taiwanese patients with higher-risk myelodysplastic syndromes received azacitidine 75 mg/m2/day for 7 days/28-day cycle for up to six cycles. Response-evaluable patients had baseline and cycle 6 marrow assessments. Clinical outcomes are compared descriptively with those from a phase 3 study comprising mainly Caucasian patients (N = 179). Pharmacokinetics in a subgroup of Taiwanese patients are descriptively compared with a historical control of North American patients (N = 45). Results: Median age of Taiwanese patients (N = 44) was 64 years (range 36–90), and 46% had poor cytogenetics. Median number of azacitidine cycles was six (1–6). No response-evaluable patient (n = 33) achieved complete or partial remission; however, 22 patients (50%) achieved hematologic improvement, 12 of 32 patients attained RBC transfusion independence and 7 of 18 attained platelet transfusion independence. Most common grade 3–4 treatment-emergent adverse events were neutropenia (52%) and leukopenia (39%). Pharmacokinetic profiles were similar for Taiwanese (N = 12) and North American (N = 45) patients. Maximum plasma concentration was higher in Taiwanese patients; however, mean azacitidine exposure was within the range for North American patients. Conclusion: These data confirm the safety and efficacy of azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes. Clinical outcomes were generally comparable with those for Caucasian patients. No meaningful differences in azacitidine pharmacokinetics were observed for Taiwanese patients, and no initial dose adjustment is necessary.

AB - Aim: Clinical and pharmacokinetic effects of azacitidine in higher-risk myelodysplastic syndromes were established in mainly Caucasian populations. Because of inter-ethnic genotype variability of drug-metabolizing enzymes, it is important to evaluate azacitidine in populations expected to use the drug. Methods: In this single-arm study, Taiwanese patients with higher-risk myelodysplastic syndromes received azacitidine 75 mg/m2/day for 7 days/28-day cycle for up to six cycles. Response-evaluable patients had baseline and cycle 6 marrow assessments. Clinical outcomes are compared descriptively with those from a phase 3 study comprising mainly Caucasian patients (N = 179). Pharmacokinetics in a subgroup of Taiwanese patients are descriptively compared with a historical control of North American patients (N = 45). Results: Median age of Taiwanese patients (N = 44) was 64 years (range 36–90), and 46% had poor cytogenetics. Median number of azacitidine cycles was six (1–6). No response-evaluable patient (n = 33) achieved complete or partial remission; however, 22 patients (50%) achieved hematologic improvement, 12 of 32 patients attained RBC transfusion independence and 7 of 18 attained platelet transfusion independence. Most common grade 3–4 treatment-emergent adverse events were neutropenia (52%) and leukopenia (39%). Pharmacokinetic profiles were similar for Taiwanese (N = 12) and North American (N = 45) patients. Maximum plasma concentration was higher in Taiwanese patients; however, mean azacitidine exposure was within the range for North American patients. Conclusion: These data confirm the safety and efficacy of azacitidine in Taiwanese patients with higher-risk myelodysplastic syndromes. Clinical outcomes were generally comparable with those for Caucasian patients. No meaningful differences in azacitidine pharmacokinetics were observed for Taiwanese patients, and no initial dose adjustment is necessary.

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DO - 10.1111/ajco.12659

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