Mastering the Art and Science of Integrative Cancer Medicine


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Stage 3 Melanoma Patient, Stable

A 61-year-old woman consulted with me early in 2021 for help with her stage 3 melanoma which began in 2018 and which was initially excised from her back. It then subsequently spread to lymph nodes in her groin. Her oncologist wanted her to start on immunotherapy to protect against brain and other metastases. She was resistant to this suggestion, having read the side effects, and consulted with me.

Other mutations that are not uncommon in melanoma, such as the V-600 E mutation, “has also led researchers to accomplish newer therapeutic strategies that lead to improved disease-response and grant survival benefits. Vemurafenib, a BRAF inhibitor agent, is one of the few available targeted therapies that is FDA approved and provides promising results in metastatic disease. However, its resistance at an early stage is of great concern. Recent implementation of combinational therapies including targeted therapy, immunotherapy, and biological agents has appealed many researchers to define the adjunctive role of available therapies and their limitations in advanced stage and metastatic melanoma.”21

Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation. Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600–mutated melanoma.22

The lesson here, being aware of this more updated clinical research, is that modern oncology continues to develop strategies for cancer treatment. And the additional lesson is that there are combinations of integrative therapies that can support the use of these therapies so as to prevent serious side effects and to potentiate them. A discussion of this subject is beyond the scope of this article. Suffice to add here that a well-recognized potential side effect of immunotherapy is autoimmune conditions.

Regarding lab tests pertinent to melanoma, her LDH (a good tumor marker in melanoma) continues to be normal, as does her beta 2 microglobulin.

Her serum S-100B levels are high at 137 (0-96). This is a great marker for micrometastases in melanoma. S100 calcium-binding protein B (S100B) is a protein of the S-100 protein family. S100 proteins are localized in the cytoplasm and nucleus of a wide range of cells and are involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. This protein may function in the proliferation of melanoma cells, as well as in other cancers, notably when there is nervous system damage. Her serum CoQ10 level is normal and has stayed normal. When this is low, there is a greater risk of metastases.23

I advised the patient to add high-dose quercetin to her program, and perhaps a general antihistamine, which published studies suggest may help in melanomas. In a research letter, “Antihistamines May Improve Survival Among Patients with Malignant Melanoma” in the journal Allergy, researchers reported that the common allergy medications desloratadine and loratadine may be associated with improved survival in patients with malignant melanoma. And the ASCO Post reported in May 2020, “Antihistamines May Improve Survival Among Patients with Malignant Melanoma.”24 Also, “Users of two common antihistamines—desloratadine and loratadine—have lower mortality rates from cutaneous malignant melanoma than patients who use other antihistamines,” researchers reported in March 2020.25 

In addition to a robust oral protocol and IV vitamin C, she was started on subcutaneous mistletoe, and developed a significant rash with even the lowest strength, so this dose was titrated for an optimal response. Mistletoe is a form of immunotherapy, though this is not often recognized or acknowledged in oncology. From the beginning, this woman was very sensitive to low doses of subcutaneous mistletoe, which enables us to see that there are no formulas in medicine, and that protocols must be adjusted to the individual.

She continues as my patient and is clinically doing well. Follow-up MRI and CT have both been stable with no progression of her melanoma.

What this case demonstrates is how to help someone with an aggressive cancer type:

  • By understanding the intricacies of her cancer and her terrain, and the importance of specific lab test markers in melanoma;
  • Helping her to steer through the oncology world and to remain with a stable but dangerous cancer;
  • Maintain a good quality of life;
  • Follow a well thought out integrative cancer program;
  • Prepare for any eventual need for immunotherapy, which her oncologist wants her to do now, but she is hesitant.

She is a very pleasant and intelligent person who has researched her condition well, and who understandably is under stress regarding her condition and the advice she is receiving. She continues to be reticent to undergo immunotherapy, due to the potential of side effects. Of course, if her subsequent MRIs and CTs show any further spread of this aggressive cancer, she is open to immunotherapy.


Rekindling Passion Every Day

In the beginning, what works best for me, when I walk through the door into an exam room to see a cancer patient, or when the patient walks into my office, is to recognize and feel the individuality of that patient. My initial task is to empty myself of any preconceived notions I may have, and to strive to become the best integrative cancer physician I may be. 

I observe the following things:

  • What is my initial sense when the patient walks in?
  • What is his or her state of mind?
  • Do I feel fear and anxiety from the patient, or confidence and trust?

It is the manner in which I combine and make sense out of what I feel and perceive with what I know about the person’s terrain and the cancer itself, including treatments, that the art and alchemy of discovering a path towards healing for the person in front of me may come to fruition. 

In taking this approach, we rediscover each day, through our patients, our passion for this work. This passion can help each of us deal with the issues of life in which we ourselves may be struggling. That helps us to find our way to the feeling that we have fulfilled our task for that person and that day. This is holy work, and it is holy ground. 

www.robertzievemd.com


References

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  2. Printz C. Radiation Treatment Generates Therapy Resistant Cancer Stem Cells from Aggressive Breast Cancer Cells. Cancer. July 1, 2012; Radiation-induced reprogramming of breast cancer cells. 2012 Jul 1;118(13):3225. doi: 10.1002/cncr.27701.
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  9. Zhisong Fan et al. G-CSF in Human Gastric Cancer Leads to Poor Survival.Med Sci Monit. 2018 Mar 23, 24: 1701-1711.
  10. Waller EK. The role of sargramostim (rhGM-CSF) as immunotherapy. Oncologist. 2007;12 Suppl 2:22-6. 
  11. Mulcahey N. A Potential Decision-Making Tool for Trastuzumab Use in Breast Cancer. Cancer Res. 2009;69(16).
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  14. Menendez JA, et al. Oleic acid, the main monounsaturated fatty acid of olive oil, suppresses Her-2/neu (erbB-2) expression and synergistically enhances the growth inhibitory effects of trastuzumab (Herceptin) in breast cancer cells. Oncol Lek. 2013 Nov;6(5):1265-1270.
  15. Jae-Hoon Jeong. Quercetin-induced ubiquitination and down-regulation of Her-2/neu. J Cell Biochem. 2008 Oct 1; 105(2): 585–595.
  16. Ming Shi, et al. Catecholamine-Induced β2-adrenergic receptor activation mediates desensitization of gastric cancer cells to trastuzumab by upregulating MUC4 expression. J Immunol. 2013 Jun 1;190(11):5600-8.
  17. Abdelfatah S, Efferth T.  Cytotoxicity of the indole alkaloid reserpine from Rauwolfia serpentina against drug-resistant tumor cells. Phytomedicine. January 2015; 22(2)
  18. Ming Shi, et al. The β2-adrenergic receptor and Her2 comprise a positive feedback loop in human breast cancer cells. Breast Cancer Res Treat. 2011 Jan;125(2):351-62.
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  20. Jandial DD, et al. Induction of G2M Arrest by Flavokawain A, a Kava Chalcone, Increases the Responsiveness of HER2-Overexpressing Breast Cancer Cells to Herceptin. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547191
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