Miljenko,
With respect to DD, a clarification. You're right, we can all do it, and an example follows. But interpreting it is where many of us fall short of a fellow with your background.
Anyhow, CA4P blood infection attacks: rumor or what? Heckuva good question. To counter the tiny clue you found, here's another clue, equally tiny, on the opposite side.
>>Eur J Cancer 2000 Sep;36(14):1833-43
Vascular targeting of solid tumours: a major 'inverse' volume-response relationship following combretastatin A-4 phosphate treatment of rat rhabdomyosarcomas.
Landuyt W, Verdoes O, Darius DO, Drijkoningen M, Nuyts S, Theys J, Stockx L, Wynendaele W, Fowler JF, Maleux G, Van den Bogaert W, Anne J, van Oosterom A, Lambin P.
Department of Experimental Radiobiology/Radiotherapy, Catholic University of Leuven (KULeuven), University Hospital Gasthuisberg, Herestraat 49, B-3000, Leuven, Belgium. will.landuyt@reg.kuleuven.ac.be
Tumour-specific vascularisation may be therapeutically approached in two different ways: by antiangiogenic treatments specifically directed to dividing and migrating endothelial cells, or by agents that target principally the inadequate and ill-structured tumour vasculature. Combretastatin A-4 phosphate (combreAp), a recently synthesised prodrug (OXiGENE, Lund, Sweden), is a vascular targeting agent of the latter kind. We evaluated the effect of a single intraperitoneal (i.p.) combreAp injection on the growth of rhabdomyosarcomas syngeneic in WAG/Rij rats. Different tumour volume groups, ranging between 0.1 and 27 cm(3), were selected to assess the relationship between the size at treatment time and the response to combreAp. A double combreAp treatment (2x25 mg/kg) was investigated within the same overall aim: the relationship between growth delay and tumour size. Our results show that the systemic administration of combreAp induces a clear-cut differential growth delay in the solid rat rhabdomyosarcomas: with very large tumours (>/= 14 cm(3)), a 17.6-fold stronger effect was measured than with very small tumours (<1 cm(3)). This is the 'inverse' of the volume-response seen with the conventional therapeutic approaches (radiotherapy, chemotherapy or surgery). These combreAp antitumour responses were observed without treatment limiting systemic toxicity in the rats. With clinical digital subtraction angiography, using microsurgical cannulation of a major tumour draining vessel, and with histopathology, we demonstrate that growth delay is related to an early (within 3-6 h) and extensive breakdown of tumour blood vessels. The experiments involving a second injection also indicate a volume-dependent effect of combreAp in reducing the regrowth rate of small or large rhabdomyosarcomas. This significant differential volume-response obtained with 'selective' vascular targeting, stronger in larger tumours than smaller ones, suggests the potential of broadening the therapeutic window.
PMID: 10974632 [PubMed - indexed for MEDLINE]<<
Emphasis mine.
Are these rats so clean that there would be no blood infections for CA4P to attack? Hence the problem, if it exists, was not picked up in preclinical studies? What of management's statement about no fatalities? If the effect is as bad as the Yahoo! posts suggest, wouldn't that cause a severe adverse event, at least? Would we, or would we not have heard about this?
I'd think the attack of infections, if a real effect, would be by a different mechanism of action, so wouldn't it be fairly easy to find the offending moiety and get rid of it?
In any case, if true, the problem will slow development more than is currently anticipated by most investors, IMO. How much, I couldn't say. The odds that it's a problem are less than 50%, IMVHO. No references given to support the claim of the Yahoo! poster, nothing obvious in the literature. But I am underqualified and would have liked to have hashed this out earlier.
Cheers, Tuck |
