Tuesday, October 26, 2010

Reducing chemotoxicity - Herbs to the rescue!

"Herbal medicine reduces chemotherapy toxicity," this headline in the "highlights" section of the latest issue of Nature Reviews Drug Discovery, caught my attention.  This was the first time, I saw "herbs" casted in a positive light re: cancer care -- completely opposite to the establishment's stream-rolled opinion that herbs, generally speaking, interfere in unknown ways with current allopathic medications and medical care.

    Nausea, vomiting and diarrhea are common side-effects of irinotecan, a DNA Topo I inhibitor.  The "herb mix" in the news is PHY906, a mixture of four Chinese herbs.  The researchers found that in a mouse model of colon carcinoma, PHY906 decreased weight loss and potentiated anti-tumor activity of irinotecan.  It also increased the number of proliferative cells, decreased the number of apoptotic cells, reduced infilteration of NEUT and macrophages, and inhibited inflammatory mediators, TNFalpha, Cox2, iNOS and NFkB activity.  It also increased intestinal progenitor cell markers, such as, CD44, GPCR5, ASCL2 and induced Wnt signaling (increased Wnt3, frizzled 5 and Lrp5 levels.)  In summary, PHY906 is potent anti-cancer but inflammation reducer (one cause of toxic side-effects).  A clinical trial sponsored by Yale and  a New Haven, CT, startup, PhytoCeutica is registered under NCT00730158.  

    The basis of PHY906 is an 1800 year old cocktail consisting of Chinese peonies, Chinese liquorice, the fruit of a Chinese date tree and flowers of the Chinese skullcap plant.  Planning and conducting an herb clinical trial is not straightforward.  FDA regulations are still being developed to regulate botanical products as drugsIf PHY906 reaches clinic, its stimulatory effects on progenitors will set it apart from the other tools to manage chemotherapy GI side-effects.  The progenitor-specific effect may help in regeneration and repair of the tissue/organ.

    (Cover Art: CURE’s "A Patient’s Guide to Side Effects")

    Constellation of chemo-induced side-effects:

    There is a constellation of chemotherapy-induced side-effects and GI toxicity is just one of them.  

    Here is a brief digest of a patient booklet, published by CureToday, on chemo-induced side-effects and some of the common interventions.

    Antiemetics (such as, Aloxi, Anzemet, Kytril, Zofran and its oral spray version, Zensana) that block serotonin pathway help with Nausea and vomiting.  Other antiemetics, such as, Emend work by blocking NK1 receptor (the vomiting induction pathway in brain) and are effective.  Lifestyle changes, such as, avoiding food and smells that trigger nausea are helpful.  Sensory or motor neuropathy can occur even years after chemotherapy.  Clinical depression  is also a major concern.  Motor (muscle weakness) and sensory (pain, numbness, tingling) symptoms can be managed with anticonvulsants, lidocaine patches and alternate approaches, including, yoga, physical therapy, etc.  Pain is an issue for over 90% of the patients and in ~50% it is chronic.  Morphine for chronic pain remains a preferred choice.  Duragesic and buprenorphine skin patches have fewer side effects than morphine.  Prialt, isolated from a snail toxin, binds Ca2++ ions and blocks a different pathway than morphine, is directly injected into spinal fluid.  Pain management is often handled by Pain Specialists.  Oral mucositis is a problem, particularly with 5FU and methotrexate use.  It is generally  managed with OTC pain medications.  The latest drugs for mucositis are Kepivance and GelclairAcne-like or rosacea-like rashes are commonly seen with drugs targeting EGF-EGFR pathway, including Tarceva, Erbitux, Tykerb and Vectibix.  Rash is actually considered a biomarker for these drugs’ efficacy, and can be easily managed using antibiotics, antihistamines and acne or eczema creams.  Procrit or Aranesp are used for anemia management.  Neutropenia is actively monitored and if neutrophil counts go down, Neupogen or its longer acting cousin, Neulasta, which requires just one injection in three weeks, is used.  A newer option is MozobilHair loss may be near complete in patients on Adriamycin, Taxol and Taxotere, or much less, as with Oncovin and Gemzar.  Wigs and hair care are recommended.  Hair growth generally resumes after cessation of chemotherapy.  Fatigue could be due to anemia or low thyroid function.  Ritalin and Provigil can also be prescribed for fatigue.

    *Palliative care is an extremely important part of cancer treatment 
    and cannot be overlooked!

    Further Reading
    • The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity. Lam W, et al., Science Translational Medicine 2010 Aug 18;2(45):45ra59. | PubMed | Scholar | 
    • How an 1,800-year-old herbal mix heals the gut. Ewen Callaway. Published online 18 August 2010. Nature News | FullText | DOI | 
    • CURE’s "A Patient’s Guide to Side Effects," CURE Patient Guides| FreePDF | FullText |
    Alza Corp (now J & J)- Duragesic (fentanyl)
    Amgen- Aranesp (darbepoetin alpha), Kepivance (palifermin), Neupogen (filgrastim; G-CSF), Neulasta (pegfilgrastim), Procrit (epoetin alfa), Vectibix (panitumumab)
    Cephalon - Modafinil (modafinil)
    Elan - Prialt (Ziconotide)
    Eli Lilly - Gemzar (gemcitabine), Oncovin (vincristine)
    Genzyme - Mozobil (plerixafor)
    GSK - Tykerb (lapatinib), Zofran (ondansetron) and its oral spray version, Zensana)
    Merck - Emend (aprepitant)
    Pharmacia (merged with Pfizer) - Adriamycin (doxorubicin)
    Reckitt & Colman - Buprenex (Buprenorphine)
    Roche - Kytril (granisetron) -
    Sanofi-Aventis - Anzemet (dolasetron), Taxotere (docetaxel)
    Telik - Telintra (Ezatiostat, TLK199)

    //edited.may 20, 2012

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