Does chemotherapy have long-term side effects beyond the known immediate toxicity? Though most patients never get a chance to consider, let alone voice a concern over long-term side-effects of chemo as they get herded through the traditional oncological procedures, new studies suggest they exist. Depending on the regimen of chemotherapy chosen, potential long-term adverse effects include premature menopause, cognitive impairment, cardiovascular and neuromuscular toxicity, and secondary malignancies as the chemo may kill rapidly replicating cells but then leaves circulating tumors cells to thrive. Recently, two groups of investigators have studied whether premature aging is also a possible effect.

imagesSanoff and colleagues (1) cite evidence that “adjuvant chemotherapy may confer effects consistent with molecular aging of 10 to 15 years in breast cancer patients”. The observed cellular senescence is due to the drugs activation of INK4/ARF locus on chromosome 9p21.3, which codes for the tumor-suppressor proteins p16INK41 and ARF in peripheral blood T cells. Studies have also shown that other markers of aging, including decreased leukocyte telomere length (LTL) and expression of senescence-associated cytokines such as interleukin 6 are present in a much higher degree post-chemo. (2)

Post-chemo expression of p16INK4a and ARF corresponds to an almost 15-year chronological aging in the hematologic compartment, specifically CD3+ lymphocytes. The senescence-associated cytokines VEGFA (vascular endothelial growth factor A) and monocyte chemotactic protein-1 were also persistently elevated with adjuvant chemotherapy.

Understand, chemotherapy has three main applications. It is thought to be curative for only a small number of malignancies including childhood leukemia, Hodgkin’s and non-Hodgkin’s lymphoma. It has a palliative role for most metastatic epithelial malignancies. Finally, it is used in an adjuvant role in several types of epithelial malignancies particularly breast cancer. First employed in the mid 1970s, adjuvant chemotherapy has been associated with up to a 30% relative improvement in long-term overall survival in high risk breast cancer but demonstrates significantly less absolute improvement.

Now that adjuvant chemotherapy is being recommended in nearly every cancer case, both the relative and absolute improvement in overall survival is even less impressive. With a growing number of long-term cancer survivors, we are only now able to define the delayed implications of adjuvant chemotherapy. These long-term side effects include acceleration of neurocognitive decline, musculoskeletal complications such as early onset osteoporosis, premature skin and ocular changes and the most common long-term complaint; mild to profound fatigue. This complex of problems is suggestive of early onset frailty. (3)

If I may offer some suggestions that doctors might offer patients exposed to chemotherapy, they might include:

1. Green Tea Extract (EGCg) at a daily dose of 1500-2500mg. This can help promote osteoblastic activity and decrease overall IL-5 levels.

2. Resveratrol at a dose of 10-20mg TID. Don’t be fooled into believing that drinking a glass or two of red wine supplies your resveratrol needs. A fluid ounce of red wine averages around 90 micrograms of resveratrol. The studies on resveratrol supplementation suggest 20 mg (20,000 mcg) of resveratrol is needed to positively affect aging. Therefore, 20-mg resveratrol provides approximately 220 times the amount of resveratrol found in one fluid ounce of red wine. Since a glass of wine is approximately 5 and 1/3 ounces, a person taking one 20-mg resveratrol supplement may ingest the equivalent amount of resveratrol found in 41 glasses of red wine. Needless to say, that is a lot of red wine and no one needs the alcohol. When reversing the telomere decay from the effects of chemotherapy, I suggest a higher dose of resveratrol and throughout the day. Since resveratrol has a very short half-life in the body, it is very necessary to spread out the dosage over time.

3. Liver pathway support. It is essential to support methylation and other detoxification pathways. There are numerous good products on the market available to do so and I suggest you keep patients on something for this for life.

4. Decrease brain inflammation. We use a product we’ve developed that we call BAM (Brain Anti-inflammatory Mix) but generally you want to use herbs such as Ginkgo, Turmeric, Boswelia, White Willow Bark, Ginger Root, Nettle Root Extract, Arnica Extract, and Celery seed. You can add Bacopa to this list as well as ALA, NAC, etc.

5. Heal the barriers (gut and brain) with appropriate nutrition and diet.

6. Decrease any other inflammatory causes.

Well, once again, I hope this helps!

(1) Sanoff HK et al. J Natl Cancer Inst 2014 Mar 28. Duggan C. J Natl Cancer Inst 2014 Mar 13.
(2) THE FRANZ BUSCHKE LECTURE: LATE EFFECTS OF CHEMOTHERAPY AND RADIATION THERAPY: A NEW HYPOTHESIS PHILIP RUBIN, M.D. Chairman, Division of Radiation Oncology, University of Rochester Cancer Center, Rochester, NY 14642
(3) Possible acceleration of aging by adjuvant chemotherapy: A cause of early onset frailty? Ronald Eric Maccormick, Medical Hypotheses, Volume 67, Issue 2, 2006, Pages 212–215