Thursday, June 28, 2012

Making Chemotherapy Toxicity Palatable by What You Put or Don’t on Dinner Plate

Watching what we eat and how much we eat may be an effective tool to manage the toxicity of chemotherapy drugs says this month's online article in the New England Journal of Medicine.

Alessando Laviano and Filippo Rossi Fanelli from the Sapienza University in Rome, Italy, reviewed recent research and clinical data suggesting that food intake behavior modification may improve efficacy, mitigate toxicity and increase compliance of chemotherapy treatments.
Let the dietitian into the oncologist chambers”

The appreciation that food and timing of meals may affect the efficacy or absorption (from gut) of various drugs is as old as the history of modern pharmacy -- grapefruit juice can increase the absorption of statins and blood pressure medications tipping the balance towards overdose (and toxicity). While certain drugs, like Synthroid (levothyroxine) needs empty stomach to be properly absorbed.

The link between food and chemotherapy toxicity has evolved with the discovery that cancer cell metabolism is different from normal cells. Cancer and normal cells respond differently to the availibility of nutrients (food).

Warburg's discovery that cancer cells prefer anaerobic respiration (normal cells prefer aerobic pathway) made a hundred years ago combined with the understanding unique protein and lipid metabolism and signaling pathways over the last two decades has spawned efforts by several companies to discover new drugs targeting this metabolic difference.

Cancer cells are voracious energy consumers

While normal cells may enter quiescence and go on battery power under temporary fasting conditions, the cancer cells is unable to kick-start this protective response which makes them more vulnerable to chemotherapy drug. In the absence of energy, cancer cells enter the "oxidative stress" state: they make oxygen free radicals (which are highly destructive), and since they often have lost part of DNA and protein repair machinery, they are vulnerable to outside threats, such as, chemotherapy drugs. Normal cells lie low and, thus, can escape the effects of chemotherapy drugs.

Show me the money

What is the evidence that supports cancer cells’ vulnerability under low energy state? Here is the evidence listed in support of diet management in the NEJM article:

  • Short-term starvation of activated oncogene containing yeast cells makes these cells susceptible to chemotherapy drugs.
  • Putting mammalian cell lines in an in vitro medium lacking glucose and growth factors makes them susceptible to killing by doxorubicin and cyclophosphamide drugs (both are common chemotherapy drugs).
  • Human cancer cells implanted under their skin grow poorly, even decrease in size, if these mice were temporarily starved for 2-3 days.  And, not only these tumors grew poorly in these mice, chemotherapy drugs are more effective in getting rid of such tumors. This was true for several metastic tumor types tested: melanoma, neuroblastoma and breast cancer.
  • One clinical trial with 10 patients found reduced chemotoxicity symptoms.

The future

The old school chemotherapy drugs, most targeting DNA replication or protein transcription/translational machinery in proliferating cells, are known to make a cancer patients miserable by "collateral damage" to normal bone marrow, gut lining, etc. 

The current crop of "targeted therapies" are not drone strikes either, as professed.  Most have the so-called "off-target" effects which is a euphemism for, "yes, these too kill normal cells and fucntions beyond a certain dose."  

Thus, for both old and new drugs, mangement of toxicity is an important part of cancer management, and diet management can work across the board.

Alessandro Laviano, & Filippo Rossi Fanelli (2012). Toxicity in chemotherapy--when less is more N Engl J Med, 366 (24), 2319-2320

Related Posts:

Oral Mucositis: an Underappreciated Problem in Cancer Care. May 20, 2012.
Reducing chemotoxicity - Herbs to the rescue! October 26, 2010.

1 comment:

  1. That sounds like something they would do at a hospice or something. Still, if it gets the job done, then we might as well follow it.