A phase I trial of hypoxoside as an oral prodrug for cancer therapy--absence of toxicity.
OBJECTIVE
To assess the toxicity of hypoxoside taken orally by 24 patients with lung cancer.


METHODS
Open study with patients taking 1,200-3,200 mg standardised Hypoxis plant extract (200 mg capsules) per day divided in 3 doses in order to maintain metabolite blood levels near 100 micrograms/ml.


METHODS
Patients with histologically proven squamous, large-cell or adenocarcinoma were hospitalised initially at the radiation oncology ward, Karl Bremer Hospital, Bellville, W. Cape. Thereafter they returned every 2 weeks for full clinical examinations.


METHODS
Routine biochemical and haematological measurements were done. Patients underwent regular full clinical examinations including radiographs and computed tomography scanning according to the discretion of the principal investigator.


RESULTS
Nineteen patients on hypoxoside therapy survived for an average of 4 months with progression of their primary tumours and metastases, while 5 survived for more than a year. One of them survived for 5 years and histological examination of the primary lesion showed absence of cancer. No toxic effects, in clinical examinations or biochemical or haematological measurements, were found that could be ascribed to the ingestion of hypoxoside. Only one occasion of possible drug intolerance, with anxiety, nausea, vomiting and diarrhoea, was noted.


CONCLUSIONS
The absence of toxicity warrants further investigation of hypoxoside as an oral prodrug, especially in patients with slow-growing necrotising tumours that are inoperable and have high concentrations of beta-glucuronidase and sulphatase as well as a high sensitivity for rooperol.
Smit
B J
BJ
Department of Radiotherapy, University of Stellenbosch, Tygerberg, W. Cape.
Albrecht
C F
CF
Liebenberg
R W
RW
Kruger
P B
PB
Freestone
M
M
Gouws
L
L
Theron
E
E
Bouic
P J
PJ
Etsebeth
S
S
van Jaarsveld
P P
PP
D000230:Adenocarcinoma / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000480:Alkynes / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D005069:Evaluation Studies as Topic; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
D000480:Alkynes; D000970:Antineoplastic Agents; D005960:Glucosides; D011355:Prodrugs; C087941:hypoxoside