THREE COLON CANCER BLOOD TESTS PREDICT EFFICACY/TOXICITY OF CHEMOTHERAPY

Two of the first questions that arise in  any cancer patient’s mind when their doctor proposes chemotherapy are:

Will this chemo really help me at all? and How bad is chemo going to make me feel?

Up until recently, there have been no real answers to either of these questions. The standard oncologist’s response, if the patient even dares to ask the first question, has been “Well, the reaction is different for each patient”, followed by some references to “statistics show prolonged survival time”. In my husband’s case, the answer in regards to a proposed “salvage” Erbitux regimen was a distinctly ominous “Well, it’s all we’ve got left for you.”

The typical oncologist’s answer to the second question, “How bad will it make me feel?” may include consumer-beware phrases like “some mild side effects” and “generally well-tolerated”— which I would now translate, with the wisdom of hindsight, as

“I, the doctor, have not seen very much suffering caused by this drug. However, it is my policy to insulate myself from the suffering of my patients.”

Times have changed since our last chemo discussion with John’s oncologist in 2008. There is new hope for all colon cancer patients, for whom answers to these questions may lie in three simple new blood tests.

For anyone who is a candidate for chemo with 5FU,  the base ingredient in virtually every first-line chemo regimen, a relatively new test for the DPD enzyme indicates the subset of patients for whom this particular chemotherapy will be toxic. Here’s a vital fact: 31-35% of patients treated with 5FU develop severe toxicity reactions. The enzyme largely responsible for metabolism of 5FU is the DPD enzyme. A deficiency of this enzyme causes the 5FU to linger in the system rather than passing through; the build-up of 5FU can be toxic. Complete DPD toxicity is rare, occurring in only 1% of the population, but for that 1%, 5FU can be fatal in just one dose. However, 3%- 5% of all cancer patients are partially deficient in DPD– and of those who experience severe toxicity, 43-59% are DPD deficient. A National Institutes of Health paper from 2007 went so far as to recommend that any patient suspected of DPD deficiency NOT receive 5FU chemo due to life-threatening toxicity: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2563423/.  Warnings have been added to labeling of both 5FU and oral Xeloda which state that these drugs are contraindicated for patients with known DPD deficiency.

The friend I mentioned in my last entry who was hospitalized for 2 weeks due to chemo toxicity recently requested the DPD enzyme test before deciding whether to continue with 6 months more of 5FU-based chemo. Her oncologist refused to authorize the DPD blood test for her, for reasons that are not entirely clear. The NIH paper does mention that the blood test is “labor-intensive”, but adds that there is now an alternative quick and easy breath test for DPD deficiency.

A second relatively new blood test should be of great interest to colon cancer patients who are considering chemotherapy with Ininotecan, a.k.a. “Satan in a bag”/ “evil Inino”. The UGT1A1 assay indicates those patients who are likely to experience toxicity from this drug. This link to the website for the blood test includes a thought-provoking analysis of  the troubling reluctance of oncologists and HMO’s to offer this seemingly important diagnostic test: http://www.g2reports.com/issues/DTTR/2007_2/1611334-1.html

Finally, there is a simple, non-invasive blood test with the promise of rescuing metastatic colon cancer, breast cancer, and prostate cancer patients from needless suffering caused by a chemotherapy regime that is not effective. The CTC (circulating tumor cell) test approved by the FDA in November 2007 actually shows whether a patient is responding to chemotherapy by measuring the number of tumor cells in the blood. A baseline test is done before chemo begins, followed by re-testing after one month. If the number of circulating cells has increased rather than decreased, it is an indication that the treatment is not effective.

The CTC test also indicates which patients are likely to have a favorable survival prognosis, as there is apparently a statistical correlation between the number of  circulating tumor cells and length of survival. A CTC result of greater than 3 cells per 7.5 mL of blood is associated with a poor prognosis.  I’m not at all sure that most cancer patients would want to be made aware of a potential poor prognosis, but surely virtually all cancer patients would want to know if they were pursuing a painful and costly treatment that was likely to be ineffective. Here is a link for the CTC test: http://www.webmd.com/cancer/news/20080128/test-may-predict-colon-cancer-survival

The bottom line for all three of these non-invasive blood tests is their really exciting potential for eliminating at least some of the suffering that is inherent in being treated with chemotherapy for cancer. It is troubling that all three are apparently infrequently offered.  Every cancer patient should be aware that these tests do exist and are currently available. Please help to spread the word. May all patients benefit…

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About surfingon

I live in Hawaii. I surf in the winter and swim in the summer. I have been a hospice volunteer with a contemplative-care oriented hospice for 25 years have been part of their team that trains new volunteers for the last 9 years. I have walked the colon cancer path with my beloved husband these past 5 years. He died very peacefully in April 2009. I now seek to share what we learned, to shed light on the many dark corners of this often mystifying, heartbreaking and heart-opening journey.
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2 Responses to THREE COLON CANCER BLOOD TESTS PREDICT EFFICACY/TOXICITY OF CHEMOTHERAPY

  1. NMS says:

    Great information. Agree with the “troubling reluctance” of oncologists to address these toxicities upfront. I asked “what if” several times, different oncs, about the “1%” DPD deficient, essentially got shrugged off, no meaningful action for or without DPD determination.

    Apparently “only” in the “next” lower level of severe toxicity category, ca 3%-6% wide, we deal with 5FU toxicity several ways: 1. least toxic 5FU formula (generic uracil-tegafur, UFT); 2. started at low(est) dose for continuous use; 3. less/non-toxic biomodulation in place of leukovorin (cimetidine for very common E-selectin biomarker); 4. specific nutrition, enhanced glutamine (grams), vitamin C (grams, 5x/day), zinc, niacin(amide) for stomatitis on top of other nutrients. These tactics delay and reduce toxicity, which may still require reduction or discontinuation if the dose is still too high.

    DPD inhibited drugs (UFT, TS-1) bypass most of the variable blood levels inherent in non-inhbited 5FU drugs, reducing the window of vulnerability. This paper, http://www.nature.com/bjc/journal/v90/n5/full/6601619a.html#bib17,
    compared two years of continuous treatments with low side effect profiles for UFT vs UFT+PSK.

    Getting good response on CA19-9, down 56%, 5+ months post surgery, 4 months 5FU related chemo.

  2. Holly Thomas says:

    I just wanted to let you know that ITT Labs located in Birmingham, AL is performing a test to predict toxicity to 5-FU based drugs. A large percentage of the cases of 5-FU toxicity are caused be a deficiency in the DPD enzyme. This test actually measures DPD enzyme activity and is a very reliable method of predicting toxicity to 5-FU or Xeloda (capecitabine) or determining if a deficient DPD enzyme is the cause of toxicity. Right now we are offering the test for $225.00 and we return the results to the oncologist within 2-3 business days. Please check out our website at http://www.ittlabs.com if you have any questions about the assay or call the lab at 205-533-7162.

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