Body composition & Docetaxel (Taxotere)

[pjoshea13]

New study below.

Actually from 2016, but PubMed presumably wasn't carrying the "Clinical Nutrition ESPEN" journal back then. (Anyone ever see a copy? LOL) It's mostly an Irish study with one Canadian.

A note on BMI & visceral fat:

BMI is a low-tech estimate of visceral fat. All you need is weight & height to do the calculation. There are many studies showing that men with higher BMIs have poorer PCa survival. But BMI is not accurate, & for many men, it overstates visceral adiposity.

It can also understate it. A Dean Ornish low-fat (10%) diet can result in a low BMI, but it is a very high carbohydrate diet & is associated with elevated triglycerides. A high-carb diet exposes the body to elevated glucose levels. The body's response is to convert excess glucose to triglycerides & store them (in fat cells). Triglycerides are preferentially stored as visceral fat. It is a hormonally active fat & quite dangerous. Periprostatic fat, for instance, is associated both, with increased PCa risk & increased aggressiveness.

In the new study of Taxotere use in CRPC cases, we get the seemingly paradoxical finding that a:

"... high volume of visceral fat and BMI <25 kg/m2 are associated with reduced survival in patients with castrate resistant prostate cancer being treated with docetaxel chemotherapy"

A BMI of 18.5 to <25 is considered "normal", i.e. desirable. How can one have a normal BMI & excessive visceral fat? The Ornish diet is perfect for lowering BMI & increasing fat stores around the internal organs. You can't see or pinch this fat - only a scan can determine how much is being carried.

The phenomenon is known as TOFI (thin-outside-fat-inside). [2]

Anemia was also found to be associated with a "shorter overall survival".

Red blood cell levels are affected by testosterone [T] levels. Men with castrate T tend to have a RBC at the bottom of the observed range, or lower.

Oxygen is transported from the lungs to cells via the hemoglobin in red blood cells. Iron is required to make hemoglobin. However, anemia in CRPC cases is likely due to a shortage of red blood cells - not a shortage of iron. & yet, according to Dr. Myers, GPs regularly prescribe iron to men with anemia. Men with PCa should never supplement with iron. The study doesn't mention if/how men were being treated for anemia, so we don't know if iron was a survival risk factor.

With a shortage of oxygen, PCa cells become hypoxic. This causes the production of hypoxia-inducible factor-1alpha [HIF1A]. This is bad news, since HIF is involved in aggressive cell survival, angiogenesis & treatment resistance.

A nitroglycerine patch can help improve the blood supply to the tumor & may delay the appearance of HIF1A.

Also from the study: "Sarcopenia was present in 47%" of cases. This is a loss of muscle mass, which of course happens with castration. Resistance exercise can counter it.

Sarcopenia was not associated with survival, but "sarcopenia and low {muscle attenuation} are associated with neutropenia".

{"Neutropenia ... is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood.[1] Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria, bacterial fragments and immunoglobulin-bound viruses in the blood.[2] Patients with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening (neutropenic sepsis)." [3]}

"DLT" might be dose-limiting toxicity?

Interesting PCa study from a bunch of nutritionists. Food for thought for those contemplating Taxotere. Suggestive of changes that might improve survival.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/285...

Clin Nutr ESPEN. 2016 Jun;13:e39-e45. doi: 10.1016/j.clnesp.2016.04.001. Epub 2016 May 6.

Impact of body composition parameters on clinical outcomes in patients with metastatic castrate-resistant prostate cancer treated with docetaxel.

Cushen SJ1, Power DG2, Murphy KP3, McDermott R4, Griffin BT5, Lim M4, Daly L6, MacEneaney P7, O' Sullivan K8, Prado CM9, Ryan AM6.

Author information

1

School of Food & Nutritional Sciences, University College Cork, Cork, Ireland. Electronic address: [e-mail].

2

Department of Medical Oncology, Mercy & Cork University Hospitals, Cork, Ireland.

3

Department of Radiology, Cork University Hospital, Cork, Ireland.

4

Department of Medical Oncology, St. Vincents University Hospital, Dublin, Ireland.

5

School of Pharmacy, University College Cork, Ireland.

6

School of Food & Nutritional Sciences, University College Cork, Cork, Ireland.

7

Department of Radiology, Mercy University Hospital, Cork, Ireland.

8

School of Mathematical Sciences, University College Cork, Ireland.

9

Alberta Institute for Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada.

Abstract

BACKGROUND:

Body composition may influence clinical outcomes of certain chemotherapeutic agents. We examined the prognostic significance of skeletal muscle mass and adipose tissue on docetaxel toxicity and overall survival in patients with metastatic castrate resistant prostate cancer (mCRPC).

METHODS:

A retrospective review of patients medical records with mCRPC, treated with docetaxel was conducted. Body composition parameters (skeletal muscle mass, muscle attenuation [MA], visceral and subcutaneous adipose tissue) were measured at L3 by computed tomography (CT) and defined using previously established cut points. Toxicity profile was assessed after 3 cycles of the drug and graded according to the National Cancer Institute Common Toxicity Criteria (version 4). Overall survival was analysed.

RESULTS:

Overall 63 patients, mean age 69 years (SD 8.3), were included. Sarcopenia was present in 47% (n = 30) and of these 26.7% (8/30) were sarcopenic obese. Common toxicities (all grades) observed included fatigue (80.9%), pain (46%), and constipation (34.9%). DLT occurred in 22 (34.9%) patients; of these 10 patients (15.8%) experienced dose reductions and 12 patients (19%) experienced dose terminations. Measurements of adiposity were not predictive of DLT, however 59.1% patients who had a combination of both sarcopenia and low MA experienced DLT compared to 29.3% of patients without sarcopenia and low MA (p = 0.021). Skeletal muscle index and MA were significantly lower in patients who experienced neutropenia (grade I-II) (46.5 cm2/m2 vs. 51.2 cm2/m2, p = 0.005) compared to their counterparts (24.6 HU vs. 32.2 HU, p = 0.044). Neither sarcopenia nor sarcopenic obesity was associated with overall survival. In multivariate analysis, BMI ≥25 kg/m2 (HR: 0.349, CI: 0.156-0.782, p = 0.010) was a significant predictor of longer overall survival and both visceral fat index ≥ median 58.7 cm2/m2 (HR: 2.266 CI: 1.066-4.814, p = 0.033) and anaemia (HR: 2.81, CI: 1.297-6.091, p = 0.009) were significant predictors of shorter overall survival.

CONCLUSIONS:

Sarcopenia and low MA are associated with neutropenia (grade I-II). Furthermore, presence of anaemia, high volume of visceral fat and BMI <25 kg/m2 are associated with reduced survival in patients with castrate resistant prostate cancer being treated with docetaxel chemotherapy.

Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:

Body composition; Chemotherapy; Docetaxel; Prostate cancer; Sarcopenia

PMID: 28531567 DOI: 10.1016/j.clnesp.2016.04.001

[2] en.wikipedia.org/wiki/TOFI

[3] en.wikipedia.org/wiki/Neutr...

[bdriggers]

I wonder how this applies to post treatment. Before my diagnosis, I was 6 foot 1 inch and 300 pounds. Today, I'm 190lbs. My BMI is 26 per my fancy scale. Since visceral fat is hormonal active, my weight and lifestyle may have contributed to the development of my Cancer, but now, might the weight lose and lower BMI help fight BCR. I follow the Mediterranean diet as close as I can. Anyway, that's my thought on it.

[pjoshea13 in reply to bdriggers]

With the Med diet at up to 40% fat, your triglycerides are presumably well under control - along with visceral fat.

The U.S. food pyramid encourages a poor fat:carb ratio. Ornish goes to an extreme that few can follow, but too many grab the LO-Fat options in the supermarket, believing them to be healthier.

Britain is currently the "fat man of Europe". In 2016, the National Obesity Forum advised "that people should eat more fat, reduce carbohydrates and stop counting calories".

Naturally there was a backlash, with "experts" explaining why the advice was dangerous. The NOF position was that people following government recommendations were simply getting fatter.

NOH: "Clinicians – rather than researchers or academics – who actually deal with patients have been almost 100% supportive.”

-Patrick

[DonUSNA73]

I wonder if the > 25 BMI being a predictor of longer survival was really an indication that the sickest subjects were not eating much and so had lower BMI?

[pjoshea13 in reply to DonUSNA73]

Don,

But those men would not also have had the highest levels of visceral fat.

Good thought though.

-Patrick