tumor | The Healthy Living Group

Retinoic acid may improve immune response against melanoma — an article from Science Daily.

Myeloid derived suppressor cells (MDSC) play an important role in tumor progression. In cancer patients, the presence of MDSCs is associated with low survival rates and tumor recurrence.

MDSCs have a remarkable ability to suppress T-cell responses and to modulate the fate of multiple cells of the innate immune system. MDSCs utilize multiple mechanisms targeting the effector functions of cells involved in both the innate and adaptive immune responses to suppress anti-tumor immunity.

As stated in the article, retinoic acid stimulates MDSC to differentiate into immune-supporting cells. In addition, All-trans-retinoic acid (ATRA) is a potent differentiating agent, stimulating cancer stem cells to differentiate into less aggressive/resistant cells.

In the new study that has just started enrollment, All-trans retinoic acid (brand name – Vesanoid), is being used at a dose of 150 mg/m2 orally for 3 days surrounding each of the first four infusions of pembrolizumab. There are multiple studies that are ongoing, evaluating the combination of ATRA with chemotherapy and immunotherapy, ranging from doses of 20 mg/m2 up to 150 mg/m2.

ATRA is not specific to the treatment of melanoma; it may be used as an adjunct when treating any cancer.

healthyliving August 15th, 2019

Posted In: cancer care

Tags: all-trans-retinoic acid, ATRA, immune, immune response, MDSC, melanoma, myeloid derived suppressor cells, research, retinoic acid, stem cells, study, tumor, tumor progression

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Low-dose Chemotherapy Protocol Relies on Normalization of Tumor Blood Supply – an article from Massachusetts General Hospital.

If you search metronomic chemotherapy at clinicaltrials.gov, you will find at least 178 citations. While most oncologists will tell you that either low dose chemotherapy does not work, or that there has not been a randomized trial comparing standard of care to low dose metronomic, this concept is attracting plenty of attention from the academicians.

While cytotoxic chemotherapy works only through direct killing of cancer cells (and normal cells), low dose metronomic chemotherapy targets tumor vasculature, improves the host anti-cancer immune response, improves blood supply to the tumor (thereby increasing chemotherapy delivery to the tumor, as well as oxygen delivery, which then turns off HIF-1 alpha), and improves the tumor stroma to favor a host anti-tumor response.

Unfortunately, one size never fits all, so even low dose metronomic chemotherapy needs to be altered (dose and frequency) according to tumor response. The data continues to mount, and in the near-future, maximum tolerated dose chemotherapy, in the treatment of solid tumors, will no longer be the norm.

healthyliving July 8th, 2019

Posted In: cancer care

Tags: chemotherapy, low dose, low-dose chemotherapy, maximum tolerated dose, tumor, tumor treatment

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“Circulating Tumor Cells Predictive of Adjuvant Radiotherapy Benefit in Early Breast Cancer” – an article from Cancer Therapy Advisor can be accessed here.

This article validates what I have been proposing for quite some time; we should be checking for circulating tumor cells (CTCs) in early stage cancer.

In the US, we have a test called CellSearch, to search for CTCs in breast, prostate, and colorectal cancer. This test is FDA approved to help physicians make clinical decisions in patients with metastatic breast, prostate, and colorectal cancer.

We know the greater the number of CTCs, in a patient with metastatic cancer, the worse the prognosis. This study found that approximately 20% of patients with early stage breast cancer had CTCs. This study also showed that more aggressive treatment, adding radiation therapy, in those with CTCs, improved survival.

One of my mantras has always been, “the practice of medicine lags far behind the science of medicine.” This scientific data can and should be applied to the practice immediately. On early stage cancers, we should be checking for CTCs. If we are dealing with breast, colorectal, or prostate cancer, we can use the CellSearch test for those in the U.S. If it is a different type of cancer, we will need to send the patients’ blood outside of the country (such as a lab in Germany), where they test 6 other genetic markers for CTCs. If the patient has early stage cancer and CTCs, in my opinion, the adjuvant or neoadjuvant treatment should be continued until the CTCs are zero.

healthyliving February 7th, 2019

Posted In: cancer care

Tags: breast cancer, cancer, cancer care, radiotherapy, tumor

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Here is another publication on the use of low dose chemotherapy, but instead of being delivered in a metronomic fashion, one of the chemotherapy drugs was delivered in a continuous fashion. You can read the article on the National Institutes of Health website, by clicking the title below.

Low-Dose Continuous 5-Fluorouracil Combined with Leucovorin, nab-Paclitaxel, Oxaliplatin, and Bevacizumab for Patients with Advanced Pancreatic Cancer: A Retrospective Analysis

As I have previously mentioned, the longer the interval between chemotherapy dosing, the more likely cancer resistance will ensue.

In the current work, 1-year survival was 82%, versus 45% reported for FOLFIRINOX (standard of care), and median overall survival was 19 months, exceeding the 11.1 months for FOLFIRINOX. The authors conclude with the following, “In spite of the depressing statistics resulting from mostly negative trials, oncologists continue to accept the marginal benefits of currently sanctioned therapies for pancreatic cancer…There is no conclusive evidence that these treatment protocols are better than the 5FU-based regimens which were used in the 1980s and 1990s.”

Where and how did the concept of maximum tolerated dose chemotherapy (MTD) arise? MTD protocols were developed initially in the context of treating childhood leukemias and lymphomas; their extended clinical applications to the treatment of solid tumor malignancies were based largely on the therapeutic successes observed in the treatment of Hodgkin’s Disease and childhood ALL.

Therapeutic modeling in solid tumors was largely based on the growth parameters defined by the growth of leukemia cells. The primary therapeutic target in the leukemias/lymphomas is the abnormal cancer stem cell population of the bone marrow/lymph node. This target is more amenable to treatment with cytotoxic drugs that block cell cycle proliferation than are solid tumors, as the propagation of abnormally dividing cells comprises the primary cancer phenotype.

Solid tumor malignancies develop a phenotype that is a product not only of genetically induced cell cycle dysregulation, but also as a consequence of the abnormal microenvironment created by the tumor mass. The net result is a tumor whose proliferative capacity is generally restricted to its outer margins, thereby seriously limiting the potential efficacy of cancer drugs that target dividing cells.

Bottom line: We are still using chemotherapy dosing for solid tumors based on studies and trials treating leukemias/lymphomas, when in fact, these are two entirely different disease processes. It is time for a Wake-UP Call!

healthyliving October 1st, 2018

Posted In: cancer care

Tags: cancer care, chemotherapy, solid tumor, tumor

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