A phase I toxicity study of human rDNA interferon in patients with solid tumours.

2.50
Hdl Handle:
http://hdl.handle.net/10541/108055
Title:
A phase I toxicity study of human rDNA interferon in patients with solid tumours.
Authors:
Wagstaff, John; Chadwick, G; Howell, Anthony ( 0000-0002-6233-719X ) ; Thatcher, Nick; Scarffe, J Howard; Crowther, Derek
Abstract:
This study was designed to evaluate the clinical tolerance to multiple IM injections of rDNA-produced human alpha-2 interferon (IFN) (Schering-Plough 30500) in patients with solid tumours. IFN was administered in escalating IM doses in separate groups of patients daily for 14 days and then twice weekly for a further 10 weeks. The dosage levels were 1, 3, 10, and 30 million U/injection. Subjective toxicity could be divided into two types, acute and chronic. The acute reactions took the form of an influenza-like syndrome consisting in chills, rigors, headache, tremor, nausea, vomiting, and myalgia. These symptoms were dose-related but tachyphylaxis developed with continued dosing. The chronic toxicity consisted of malaise, lethargy, fatigue, anorexia, and confusion. These symptoms were not so dose-dependent and tended to become more severe with prolonged treatment. Objective toxicity consisted of myelosuppression and liver dysfunction. Granulocyte counts below 1.0 X 10(9)/l were seen in three patients at the 30-million-U level, with platelet counts less than 100 X 10(9)/l in two of these. Elevation of the liver enzymes were seen in all five patients treated at 30 million U, but returned to normal after 1 week without IFN in all but one patient. A tolerable dose (IM) for phase II/III studies lies between 3 and 10 million U for daily scheduling and between 10 and 30 million U for twice-weekly injections.
Affiliation:
Cancer Research Campaign Department of Medical Oncology, University of Manchester, Christie Hospital and Holt Radium Institute, Wilmslow Road, M20 9BX Manchester, England.
Citation:
A phase I toxicity study of human rDNA interferon in patients with solid tumours. 1984, 13 (2):100-5 Cancer Chemother Pharmacol
Journal:
Cancer Chemotherapy and Pharmacology
Issue Date:
1984
URI:
http://hdl.handle.net/10541/108055
DOI:
10.1007/BF00257123
PubMed ID:
6467493
Type:
Article
Language:
en
ISSN:
0344-5704
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorWagstaff, Johnen
dc.contributor.authorChadwick, Gen
dc.contributor.authorHowell, Anthonyen
dc.contributor.authorThatcher, Nicken
dc.contributor.authorScarffe, J Howarden
dc.contributor.authorCrowther, Dereken
dc.date.accessioned2010-07-21T11:59:06Z-
dc.date.available2010-07-21T11:59:06Z-
dc.date.issued1984-
dc.identifier.citationA phase I toxicity study of human rDNA interferon in patients with solid tumours. 1984, 13 (2):100-5 Cancer Chemother Pharmacolen
dc.identifier.issn0344-5704-
dc.identifier.pmid6467493-
dc.identifier.doi10.1007/BF00257123-
dc.identifier.urihttp://hdl.handle.net/10541/108055-
dc.description.abstractThis study was designed to evaluate the clinical tolerance to multiple IM injections of rDNA-produced human alpha-2 interferon (IFN) (Schering-Plough 30500) in patients with solid tumours. IFN was administered in escalating IM doses in separate groups of patients daily for 14 days and then twice weekly for a further 10 weeks. The dosage levels were 1, 3, 10, and 30 million U/injection. Subjective toxicity could be divided into two types, acute and chronic. The acute reactions took the form of an influenza-like syndrome consisting in chills, rigors, headache, tremor, nausea, vomiting, and myalgia. These symptoms were dose-related but tachyphylaxis developed with continued dosing. The chronic toxicity consisted of malaise, lethargy, fatigue, anorexia, and confusion. These symptoms were not so dose-dependent and tended to become more severe with prolonged treatment. Objective toxicity consisted of myelosuppression and liver dysfunction. Granulocyte counts below 1.0 X 10(9)/l were seen in three patients at the 30-million-U level, with platelet counts less than 100 X 10(9)/l in two of these. Elevation of the liver enzymes were seen in all five patients treated at 30 million U, but returned to normal after 1 week without IFN in all but one patient. A tolerable dose (IM) for phase II/III studies lies between 3 and 10 million U for daily scheduling and between 10 and 30 million U for twice-weekly injections.en
dc.language.isoenen
dc.subjectCanceren
dc.subject.meshBlood-
dc.subject.meshBone Marrow-
dc.subject.meshDNA, Recombinant-
dc.subject.meshDrug Administration Schedule-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshInterferon Type I-
dc.subject.meshLiver-
dc.subject.meshNeoplasms-
dc.titleA phase I toxicity study of human rDNA interferon in patients with solid tumours.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Medical Oncology, University of Manchester, Christie Hospital and Holt Radium Institute, Wilmslow Road, M20 9BX Manchester, England.en
dc.identifier.journalCancer Chemotherapy and Pharmacologyen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.