Phase II Study of Arginine Deprivation Therapy With Pegargiminase in Patients With Relapsed Sensitive or Refractory Small-cell Lung Cancer.
Clin Lung Cancer
; 21(6): 527-533, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32859536
ABSTRACT
BACKGROUND:
Pre-clinical studies indicated that arginine-deprivation therapy using pegylated arginine deiminase (pegargiminase, ADI-PEG 20) may be effective in patients with argininosuccinate synthetase 1 (ASS1)-deficient small-cell lung cancer (SCLC). PATIENTS ANDMETHODS:
Patients were enrolled into either a 'sensitive' disease cohort (≥ 90 days response to first-line chemotherapy) or a 'refractory' disease cohort (progression while on chemotherapy or < 90 days afterwards or ≥ third-line treatment). Patients received weekly intramuscular pegargiminase, 320 IU/m2 (36.8 mg/m2), until unacceptable toxicity or disease progression. The primary endpoint was tumor response assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with secondary endpoints including tolerability, pharmacodynamics, and immunogenicity.RESULTS:
Between January 2011 and January 2014, 22 patients were enrolled 9 in the sensitive disease cohort and 13 in the refractory disease cohort. At a pre-planned interim analysis, the best overall response observed was stable disease in 2 patients in each cohort (18.2%). Owing to the lack of response and slow accrual in the sensitive disease cohort, the study was terminated early. Pegargiminase treatment was well-tolerated with no unexpected adverse events or discontinuations.CONCLUSION:
Although pegargiminase monotherapy in SCLC failed to meet its primary endpoint of RECIST-confirmed responses, more recent molecular stratification, including MYC status, may provide new opportunities moving forward.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Arginina
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Polietilenoglicóis
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Terapia de Salvação
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Resistencia a Medicamentos Antineoplásicos
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Carcinoma de Pequenas Células do Pulmão
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Hidrolases
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Neoplasias Pulmonares
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Recidiva Local de Neoplasia
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article