The effects of single dose oral hydralazine on blood flow through human lung tumours.
Hydralazine has been shown to reduce tumour blood flow and to potentiate the cytotoxicity of melphalan and bioreductive agents in mice. In order to determine whether such a strategy might have clinical potential, a study was undertaken to investigate the effects of hydralazine on blood flow through human tumours. Twenty-two patients with carcinoma of the bronchus received a single oral dose of hydralazine in the range 25 to 150 mg (0.37-2.86 mg/kg) according to age and acetylator status. Tumour blood flow was assessed by single photon emission computed tomography (SPECT) performed 10 min following intravenous 99Tcm-HMPAO on two occasions 2-8 days apart, the second being performed 60 min after hydralazine administration. In 20 evaluable patients, hydralazine caused a 38% increase in blood flow through the whole tumour (p = 0.007) and a 28% increase in flow through the tumour centre (p = 0.03) with greater increases occurring in patients sustaining greater falls in peripheral resistance. Tumour vascular resistance fell indicating active vasodilation in arterioles supplying tumours. Side-effects due to hydralazine were reported by eight patients.
Rowell
N P
NP
Department of Radiotherapy, Royal Marsden Hospital, Sutton, Surrey, U.K.
Flower
M A
MA
McCready
V R
VR
Cronin
B
B
Horwich
A
A
D000284:Administration, Oral; D000368:Aged; D002283:Carcinoma, Bronchogenic / Q000098:blood supply* / Q000000981:diagnostic imaging; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D012039:Regional Blood Flow / Q000187:drug effects; D014057:Tomography, X-Ray Computed; D014664:Vasodilation / Q000187:drug effects
D006830:Hydralazine