Induction of Differentiation as a Means of Modifying Metastatic Behaviour

Ir, Hart; Nt, Goode; Ej, Ormerod

doi:10.1007/978-1-4899-5037-6_39

Advances in Experimental Medicine and Biology

1988

DOI: 10.1007/978-1-4899-5037-6_39

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Induction of Differentiation as a Means of Modifying Metastatic Behaviour

Hart Ir¹,

Goode Nt²,

Ormerod Ej³

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1997

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Cited by 1 publication

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An Eastern Cooperative Oncology Group phase I trial of all-trans-retinoic acid and interferon-alpha: E2Y92

Schiller¹,

Neuberg²,

Burns³

et al. 1997

Invest New Drugs

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The Eastern Cooperative Oncology Group conducted a Phase I trial to determine the maximally tolerated doses of combination therapy with alpha interferon (IFN-alpha) and all-trans-retinoic acid (tRA). Fifty patients with incurable malignancies received IFN-alpha administered subcutaneously three times weekly, and tRA administered by mouth at bedtime. Doses were escalated between patient groups, starting at tRA dose level of 45 mg/m2 and 3 million units of IFN-alpha. Major, dose-limiting toxicities were attributable to either the tRA (rash, chelitis) or IFN (constitutional symptoms), and were observed only at tRA dose levels of 224 mg/m2 and 291 mg/m2, or 6 million units of IFN-alpha. The maximally tolerated dose level of 172.5 mg/m2 of tRA and 3 million units of IFN-alpha was well-tolerated, with no grade 3 or 4 toxicities attributable to therapy. One patient at the third dose level (75 mg/m2 of tRA and 3 million units of IFN-alpha) developed acute hepatic and renal failure and a metabolic encephalopathy of unclear etiology. We conclude that tRA and IFN-alpha may be safely administered together at the maximally tolerated dose of tRA as a single agent without unexpected side effects. The recommended doses of IFN-alpha and tRA for Phase II trials are 3 million units of IFN-alpha and 172.5 mg/m2 of tRA.

show abstract

An Eastern Cooperative Oncology Group phase I trial of all-trans-retinoic acid and interferon-alpha: E2Y92

Schiller¹,

Neuberg²,

Burns³

et al. 1997

Invest New Drugs

View full text Add to dashboard Cite

show abstract

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Induction of Differentiation as a Means of Modifying Metastatic Behaviour

Cited by 1 publication

References 9 publications

An Eastern Cooperative Oncology Group phase I trial of all-trans-retinoic acid and interferon-alpha: E2Y92

An Eastern Cooperative Oncology Group phase I trial of all-trans-retinoic acid and interferon-alpha: E2Y92

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