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Inflammation Alternatives

One of the most common complications of brain tumor growth is the resulting peritumoral edema (hereafter referred to simply as edema; also called oedema). Edema is a major cause of neurological deficits, an independent prognostic factor for overall survival, and often the condition which ultimately causes death in high grade brain tumor patients1.

The causes of peritumoral edema are not fully understood, but it is believed that edema forms as a result of excess fluid buildup in the extravascular space surrounding the tumor and an inability of the brain to clear this fluid due to the injured blood brain barrier. The leaky capillaries common in malignant tumor angiogenesis contribute increased permeability mediated by the release of vasoactive cytokines such as tumor necrosis factor alpha (TNF-alpha), several different interleukins, and vascular endothelial growth factor (VEGF)2,3.

In gliomas, but not in other types of low grade brain tumors, VEGF expression correlates to the degree of malignancy. Yet the grade of edema is closely related to the degree of malignancy in all brain tumors as well as the location of the tumor within the brain4. In glioblastoma, nearly all progressing tumors show a large degree of edema and those that don't are usually buffered or obstructed by cystic formations.

Because of the demonstrated role of inflammatory cytokines in edema production, especially the specific role of cyclooxygenase-2(COX-2), a wide variety of substances are available which may provide relief against edema5. The gold standard treatment against edema is a corticosteroid called dexamethasone (Decadron), however its significant adverse side-effects should encourage patients to try other edema treatment options.

Corticosteroids like Decadron are powerful and fast-acting, with dose-dependent benefits and side-effects, especially when used in large amounts over long periods. Decadron use is often necessary as a temporary, precautionary measure after surgery, but patients should generally try to wean off of Decadron if possible. Corticosteroid dosages must be tapered slowly over time to let the body's natural adrenal functions kick in and to prevent severe withdrawal-like symptoms.

Besides frequent use of MRIs, there is no reliable way to predict the extent to which brain edema must be controlled with corticosteroids, so patients are often left with the precarious goal of using trial and error methods to see if lowering a dexamethasone dosage produces any negative effects. It's important to wean yourself off dexamethasone under the supervision of a doctor, to familiarize yourself with the symptoms of brain edema, and to expect some brief withdrawal side-effects as the dosage is tapered.

1. PMID: 19473360

2. Eano.eu Article

3. Medscape.com Article

4. PMID: 6098291

5. PMID: 12576462

The follow is a summary of edema treatment methods other than corticosteroids. Most of these treatments also have demonstrated efficacy in other types of cancer as well.

  • Boswellic acid: From the Indian plant boswellia serrata. Was given Orphan Drug status by the European Union in 2005 for peritumoral edema. The effect of boswellic acids (especially the beta acids) is dose-dependent and the upper limit is unclear, however some people take more than 5,000 mg per day. Boswellic acids are also cytotoxic to glioma cells.
  • Xerecept (hCRF): This is a study drug from Neurobiological Technologies that has seen significant testing as a replacement or adjuvant drug for treating peritumoral edema. There are huge, multi-national, multi-site trials currently underway. To find the location of the nearest hospital which administers Xercept, go to http://www.braintumortrials.com.
  • Recentin (cediranib or AZD2171): This is an experimental oral, pan-VEGF angiogenesis inhibitor currently in major multi-site trials that has also turned out to be an excellent anti-edema agent. I'm not sure if it's clear whether the anti-edema effects are separate or simply from the VEGF inhibition. Several participants in the most recently updated trial were able to go off of Decadron entirely. Currently you'd have to join a trial to get it.
  • Selective COX2 inhibitors: Celebrex may be the only drug left available as a prescription COX2 inhibitor. Celebrex has been taken by 30 million Americans alone. Several leading brain tumor centers, including Duke, have conducted trials of Celebrex as an adjuvant drug to standard Temodar protocols since Celebrex appears to have an independent cytotoxic mechanism against gliomas. Try 400 mg or less.
  • NSAIDs: COX1 and COX2 inhibitors in common over-the-counter pain medications, like aspirin, ibuprofen, tylenol, etc.
  • Bromelain: around 1000 mg/day. The effects of bromelain are notoriously mild.
  • Boron: at least 3 mg/day. Boron down-regulates NF-kappaB and does a variety of other things which make it very difficult for brain tumors to thrive.
  • Curcumin: dosage is tricky because there is evidence that its bioavailability after consumption is limited. Dosages below 3 g/day (3,000 mg/day) may not be active in humans. One clinical study could not detect curcumin in blood plasma at dosages lower than 10 g/day. The highest dosage noted in clinical studies appears to be 12 g/day. Curcumin down-regulates COX2, LOX and many other inflammation-related things. A few studies have shown that piperine can increase the bioavailability of curcumin, perhaps by significant amounts, however piperine itself inhibits several important metabolism enzymes in cytochrome P-450 that are necessary for common brain tumor treatment drugs, like warfarin. So use piperine with caution.
  • Omega-3 Fatty Acids: The American Heart Association recommends 1-3 g/day of EPA + DHA fatty acids, usually from fish oil or nuts.
  • Quercetin: A common dosage appears to be 200 mg/day; inhibits NF-kappaB
  • Luteolin: LEF recommends 8 mg/day; inhibits the inflammatory cytokines interleukin-6 and interleukin 1B.
  • Stinging Nettles Extract: Several studies have shown that stinging nettle extract inhibits tumor necrosis factor-a (TNF-a) and another inflammatory cytokine called interleukin-1b (IL-1b). It also inhibits COX-2 and LOX. It has apparently been long used in Germany as a safe adjuvant remedy for arthritis.
  • Serrapeptase: I'm not sure if anybody understands why this enzyme works, but apparently it is more commonly used in Europe (as are boswellic acids). Dosage can range between 10 mg to 30 mg per day.
  • DMSO (dimethyl sulfoxide): Although fairly effective for brain edema, it must be administered intravenously and under the care of an experienced physician. Most doctors are not familiar with its use in this fashion. There are also potential side-effects. Reportedly some MDs at the NIH can administer DMSO via IV.