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Titolo:
A PHASE-I STUDY OF THE LEFT-SHIFTING AGENT BW12C79 PLUS MITOMYCIN-C AND THE EFFECT ON THE SKELETAL-MUSCLE METABOLISM USING P-31 MAGNETIC-RESONANCE SPECTROSCOPY
Autore:
PHILIP PA; THOMPSON CH; CARMICHAEL J; REA D; MITCHELL K; TAYLOR DJ; STUART NSA; DENNIS I; RAJAGOPALAN B; GANESAN T; RADDA GK; HARRIS AL;
Indirizzi:
CHURCHILL HOSP,CLIN ONCOL UNIT,IMPERIAL CANC RES FUND OXFORD OX3 7LJ ENGLAND CHURCHILL HOSP,CLIN ONCOL UNIT,IMPERIAL CANC RES FUND OXFORD OX3 7LJ ENGLAND JOHN RADCLIFFE HOSP,MRC,BIOCHEM & CLIN MAGNET RESONANCE UNIT OXFORD OX3 9DU ENGLAND MRC,CLIN ONCOL & RADIOTHERAPEUT UNIT CAMBRIDGE CB2 2QH ENGLAND UNIV TEXAS,MD ANDERSON CANC CTR,DIV MED HOUSTON TX 77030
Titolo Testata:
Cancer research
fascicolo: 23, volume: 53, anno: 1993,
pagine: 5649 - 5653
SICI:
0008-5472(1993)53:23<5649:APSOTL>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
OXYGEN-AFFINITY; HUMAN-HEMOGLOBIN; TUMOR; MANIPULATION; ACTIVATION; INDUCTION; RESPONSES; RADIATION; HYPOXIA; TISSUES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
17
Recensione:
Indirizzi per estratti:
Citazione:
P.A. Philip et al., "A PHASE-I STUDY OF THE LEFT-SHIFTING AGENT BW12C79 PLUS MITOMYCIN-C AND THE EFFECT ON THE SKELETAL-MUSCLE METABOLISM USING P-31 MAGNETIC-RESONANCE SPECTROSCOPY", Cancer research, 53(23), 1993, pp. 5649-5653

Abstract

BW12C79 stabilizes the oxyhemoglobin molecule resulting in a reversible left-shift of the oxygen saturation curve. The activity of a numberof bioreductive anticancer drugs, such as mitomycin C, may be enhanced under hypoxic conditions. Twenty-four patients with various malignancies received BW12C79 and mitomycin C. BW12C79 was administered i.v. with a loading dose (20-50 mg/kg) over 1 h followed by a maintenance infusion of 4 mg/kg/h for 5 h. Percentage modification of the oxyhemoglobin (degree of left-shift) was dose related with maximum modification of 56% and was maintained for the duration of maintenance infusion of BW12C79. Hemoglobin electrophoresis showed a fast moving band consistent with the BW12C79-oxyhemoglobin complex. Side effects at the top dose level comprised headache, nausea/vomiting, vein irritation, and myocardial ischemia. One other patient suffered from an acute encephalopathy of unknown etiology a few days following BW12C79. P-31 magnetic resonance spectroscopy of exercising calf muscles showed increased breakdown of high energy phosphate stores and a greater reduction in pH. Recovery of the high energy phosphate stores after exercise was slow. These results were consistent with reduced oxygen supply due to either a left shift of the oxygen saturation curve and/or reduced muscle blood flow. BW12C79 did not interfere with the pharmacokinetics of mitomycinC. In conclusion, this phase I study demonstrates the feasibility of achieving a significant left shift in the oxygen saturation curve in cancer patients which is maintained for at least 5 h with acceptable toxicity. The maximum tolerated dose of BW12C79 was 50 mg/kg loading infusion followed by a maintenance infusion of 4 mg/kg/h. Magnetic resonance spectroscopy results were consistent with reduced supply of oxygento exercising skeletal muscle. BW12C79 may be of potential benefit asan adjunct to bioreductive drugs in the treatment of solid tumors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 06:15:49