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Titolo:
Phase I study of the mitomycin C analogue BMS-181174
Autore:
Macaulay, VM; OByrne, KJ; Green, JA; Philip, PA; McKinley, L; LaCreta, FP; Winograd, B; Ganesan, TS; Harris, AL; Talbot, DC;
Indirizzi:
Churchillgland, Clin Oncol Unit, Imperial Canc Res Fund, Oxford OX3 7LJ, En Churchill Hosp Oxford England OX3 7LJ Canc Res Fund, Oxford OX3 7LJ, En Clatterbridge Hosp, Clatterbridge Ctr Oncol, Liverpool L63 4JY, Merseyside, Clatterbridge Hosp Liverpool Merseyside England L63 4JY 4JY, Merseyside, Div Hematol & Oncol, Detroit, MI 48201 USA Div Hematol & Oncol Detroit MIUSA 48201 l & Oncol, Detroit, MI 48201 USA Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA Bristol Myers Squibb Pharmaceut Res Inst Princeton NJ USA 08543 08543 USA Bristol Myers Squibb Pharmaceut Res Inst, Brussels, Belgium Bristol Myers Squibb Pharmaceut Res Inst Brussels Belgium sels, Belgium
Titolo Testata:
BRITISH JOURNAL OF CANCER
fascicolo: 11, volume: 77, anno: 1998,
pagine: 2020 - 2027
SICI:
0007-0920(199806)77:11<2020:PISOTM>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
BMY-25067; TOXICITY;
Keywords:
Mitomycin C analogue; BMS-181174; phase I study;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Talbot, DC Churchillgland, Clin Oncol Unit, Imperial Canc Res Fund, OxfordOX3 7LJ, En Churchill Hosp Oxford England OX3 7LJ und, Oxford OX3 7LJ, En
Citazione:
V.M. Macaulay et al., "Phase I study of the mitomycin C analogue BMS-181174", BR J CANC, 77(11), 1998, pp. 2020-2027

Abstract

BMS-181174 is an waminodisulphide derivative of Mitomycin C (MMC) with activity against a range of tumour cell lines and xenografts, including MMC-resistant tumours. In a phase I study of 82 patients with confirmed malignancy, we administered EMS-181174 at doses of 0.8-75 mg m(-2) by intravenous injection every 28 days. At least three patients were evaluated at each dose level, and 174 courses were administered. The pharmacokinetics were dose linear at EMS-181174 doses of 11.5-75 mg m(-2) and the drug appeared to undergo wide distribution. The maximum-tolerated dose was 65 mg m(-2) in previously treated patients and 75 mg m(-2) in chemotherapy-naive cases. The dose-limiting toxicity was myelosuppression, particularly thrombocytopenia, which was prolonged and cumulative. Three patients treated at 65-75 mg m(-2) died suddenly with evidence of pneumonia/pneumonitis, thought to be drug-related. Other toxicities included thrombophlebitis, possible cardiotoxicity (asymptomatic, reversible decline in left ventricular function) and renal impairment. The partial response rate was 5% (4 out of 82) overall, and 9% (3 out of 32) in patients treated at 65-75 mg m(-2). Responses occurred in treated and previously-untreated patients, including cases of colorectal cancer, non-small-cell lung cancer, ovarian cancer and adenocarcinoma of unknownprimary site. BMS181174 has anti-cancer activity but, because of its toxicity, particularly pneumonitis and thrombophlebitis, no phase II studies areplanned.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/09/20 alle ore 00:11:42