The Record... (cont'd)
Before I send to Sharon the information we just reviewed on nomenclature, company information and status, I think I'll take a look at the pharmacology and clinical data. Adis R&D Insight has very extensive information in this area. Then I can send the nomenclature and pharmacology information at the same time.
Adis gives detailed pharmacology and clinical overviews. Included are pharmacodynamics, mechanism of action, route of elimination, therapeutic trials, adverse events, drug interactions, and pharmacokinetics. They are all part of the text (/TX) field. In a drug like vatalanib, which is used to treat colorectal cancer, there is extensive data for each of the uses for the drug.
View the record below to see the pharmacology and clinical data for vatalanib. Then, go to the next page.
Pharmacology Overview:
Antimicrobial activity:
Pharmacodynamics:
Inhibits VEGF-dependent tumour growth in xenograft
models; reduces blood flow into tumour; reduces number
of primary renal cell xenografts; reduces vascular
permeability in patients with glioblastoma; inhibts
the growth of multiple myeloma cells in culture; enhances
the anti-growth effect of dexamethasone in multiple
myeloma cells
Immunogenicity:
Mechanism of action:
Tyrosine kinase inhibitors
Protein kinase inhibitors
Protein kinase modulators
Phosphotransferase (Alcohol Group Acceptor)
inhibitors
Phosphotransferase (Alcohol Group Acceptor)
modulators
Kinase inhibitors
Kinase modulators
Transferase inhibitors
Transferase modulators
Enzyme inhibitors
Enzyme modulators
Vascular endothelial growth factor antagonists
Angiogenic protein inhibitors
Protein inhibitors
Peptide antagonists
Growth factor antagonists
Intercellular signalling peptide and protein
inhibitors
Protein modulators
------------------------------------
tmax (h) (oral) 1.1 - 2 (Adult)
t (1/2) beta (h) 4.5 - 4.7 (Adult)
------------------------------------
Activity versus parent drug: unspecified parent
Clinical Overview:
Route(s) of Administration: PO
Administration Freq.(per day): , od
Adverse events:
occasional: Aphasia, Ataxia, Confusion, Deep
vein thrombosis, Dizziness, Fatigue, Headache, Nausea,
Vomiting.
Drug Interactions:
Unknown.
Adverse Events:
Clinical studies: In a phase I trial, IV and oral
formulations of vatalanib were generally well tolerated.
The most frequent adverse events (AEs) were nausea
and fatigue; two patients experienced grade 3 treatment-related
AEs and five patients discontinued the study due
to AEs/11/.
In a phase Ib trial, 19 patients with stage IC-IV
ovarian cancer received paclitaxel, carboplatin,
and vatalanib; vatalanib was dosed at 250-1250 mg/day
on days 3-21 of each 21-day cycle. The most common
adverse event (AE) was grade 1-2 hypertension. Only
one patient discontinued treatment due to an AE;
no patients experienced dose- limiting toxicity or
serious AEs/10/.
In an ongoing phase I trial, oral vatalanib (150-750
mg/day) was administered od for 28 days to 12 patients
with solid tumours (3 patients/dose level). No hepatic,
haematological or dose-limiting toxicity was observed
and dose escalation is continuing/12/.
Vatalanib had acceptable tolerability at dosages
of 500-2000 mg/day in patients with recurrent glioblastoma.
Adverse events included confusion, aphasia, gait
abnormalities, headache, fatigue, nausea, and deep
vein thrombosis/13/.
Nausea and vomiting are the dose-limiting toxicities
of vatalanib in patients with acute myeloid leukaemia
and myelodysplastic syndromes. The maximum tolerated
dose of vatalanib is 1500 mg/day in patients with
acute myeloid leukaemia and myelodysplastic syndromes/14/.
A phase I, open-label, dose-escalation and dose-expansion
study in 45 patients with metastatic renal cell carcinoma ....
[Portions of the record not shown.]
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