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Avastin.. this could be important to some here


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Posted

I received this today and wanted to share it in case it is applicable to anyone here.

Chris

New Warning Added to Avastin Cancer Drug

Genentech Inc., the maker of the cancer drug Avastin, had added a warning to their label stating a possible link between a brain condition and the use of the drug. The company states that less than .1% of patients have developed symptoms of reversible posterior leukoencephalopathy syndrome (RPLS).

Avastin is a monoclonal anti-body used to treat colon and rectal cancer. It is given by IV infusion, generally every two weeks.

If you are currently taking Avastin, talk to your doctor about the risk of developing RPLS. Although the risk is slight for most patients, it is a concern for many. More information about Avastin

Posted

Thanks for that info. I know some take avastin Alimta Combo and Found RPLS Info below:

Reversible posterior leukoencephalopathy syndrome (RPLE)

- Term first coined by Hinchey et al. in 1996 who reported on a series of 15 patients

- Has been described both in children and adults

Clinical features

- Acute to subacute onset

- Neurological symptoms:

Headache

Altered mental status / confusion / drowsiness

Visual disturbance

Hemianopsia, visual neglect, cortical blindness or Anton’s syndrome (denial of blindness, confabulation)

Seizures

Often precede other symptoms

Usually generalized tonic-clonic

May be preceded by visual aura/hallucinations

Single seizure infrequent, usually multiple

- Systemic signs

Hypertension

Usually acute onset

Can be mild to moderate OR severe (depending on patient’s usual BP)

Metabolic derangements

Hypomagnesemia

Hypocholesterolemia

Both of above present in > 50% patients with RPLE secondary to cyclosporin A

Aluminum overload

Elevated drug levels

Present in 50% patients with RPLE secondary to cyclosporin A (rate of rise may be important)

Renal failure

Worsens hypertension

Can cause fluid overload

Etiologies

Most commonly reported:

- Hypertensive encephalopathy

- Renal failure with hypertension, these patients appear to be more susceptible

- Eclampsia (pregnancy or puerpurium)

- Immunosuppressive agents and cytotoxic drugs (see below)

- Drug withdrawal (esp clonidine)

Case reports:

- Collagen vascular disorders, including SLE, PAN, Behcet’s

- TTP

- Acute porphyria

- Post organ transplantation

- Post-carotid endarterectomy (unilateral hemispheric) with reperfusion syndrome

- GBS with autonomic hyperactivity

Immunosuppressive and cytotoxic agents

- cyclosporin A

- tacrolimus / FK-506

- IFN-a

- cisplatin

- cytarabine

- IVIg

- Erythropoietin

Pathogenesis

- Not precisely known

- Rapid rise in blood pressure overwhelms normal autoregulatory mechanisms

- Leads to dilatation and leakage of cerebral arterioles causing vasogenic edema

- Posterior circulation has less sympathetic adrenergic innervation, and therefore is thought to be more susceptible to effects of rapid rise in blood pressure

Alternative hypotheses (which have largely fallen out of favor):

- Vasospasm secondary to sudden severe rise in pressure or toxin leads to ischemia and cytotoxic and vasogenic edema

- Toxic damage to blood brain barrier or vascular endothelium

Differential diagnosis

- Vascular

Infarct, especially “top-of-the-basilar syndrome” (with bilateral PCA ischemia)

Hemmorhage (congophilic parieto-occipital lobar ICH etc)

Venous thrombosis

- Infection

Encephalitis, meningitis

- Inflammatory / Autoimmune

- Postinfectious encephalomyelitis

- Vasculitis e.g. SLE

Investigations

CSF

- Usually normal

- May have mild elevation in protein

Imaging

- Changes noted below are seen in bilateral occipital and parietal lobes

- Often symmetrical but can be asymmetrical

- Primarily affects white matter, but grey can also be involved

*** Calcarine / paramedian occipital lobe is spared

- More rarely may involve brain stem, cerebellum, basal ganglia, frontal lobes

- Imaging findings are REVERSIBLE with prompt successful treatment (may take days to weeks for full reversal)

- If treatment is not promptly initiated, may progress to infarction or hemorrhage

CT / MRI

CT

Hypodense lesions

MRI

Iso- / Hypo-intense on T1

Hyperintense on T2

Iso- / Hypo-intense on DWI

Treatment

- Control blood pressure

- 10-20% decrease in MAP is usually sufficient to terminate process

- Discontinue or decrease dose of offending agents (immunosuppressive, cytotoxic)

- Treat hypomagnesemia

- Treat seizures with anticonvulsants

- Note: Phenytoin also induces metabolism of cyclosporin and FK-506

Prognosis

- Most patients recover completely with prompt treatment within hours (12-24h) to days

- Imaging findings may persist for weeks

- Can lead to poterior circulation infarction or hemorrhage if not treated promptly

- Patients do not require chronic antiepileptic treatment once imaging abnormalities have resolved

Differentiating top-of-the-basilar syndrome from RPLE

- Appropriate clinical scenario

e.g. acute hypertension, renal failure, transplant, use of immunosuppressive agent etc.

- Seizures

Uncommon in stroke, common and multiple in RPLE

- CT / MRI

Sparing of paramedian and calcarine occipital lobe in RPLE

Top-of the basilar syndrome often also involves thalamus and midbrain

Infarct is bright on DWI, whereas RPLE is iso or hypointense

- Rapid clinical / imaging resolution with appropriate treatment in RPLE

References:

Postgrad Med J 77:24-28, 2001

J. Neurol. 246:339-346, 1999

Neuroradiology 39:711-715, 1997

NEJM 334:494-500, 1996

Last update: August 2004

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