Fatigue

Contents

• Introduction

• One Patient's Experience

• Depression and Fatigue

• L-Carnitine Deficiency May Cause Fatigue

• An Anecdotal Report from an HRPC Patient with Fatigue Who is trying L-Carnitine

• References for L-Carnitine

• American ginseng (panax quinquefolius) for cancer-related fatigue (added 7/26/07.)

• Excerpt from "Choices: Living with Cancer, Dying with Dignity" on Fatigue

Introduction

For a perspective on the importance of combating fatigue, consider that a survey of more than 1000 cancer patients reported in the Annals of Oncology found that 58% complained of fatigue, more than double the patients who complained about pain (22%) or about nausea and vomiting (18%) (Stone P et al. Ann Oncol. 2000;11;971-975.)

Various ways of combating fatigue are covered on this page as well as the other, single patient page.  Note also, that exercise is the only method that has shown consistent evidence of benefit for combating fatigue. 

The National Cancer Institute (NCI) has an excellent website that discusses most, if not all, of the side effects of cancer, among them fatigue. Go to this website and then click on the fatigue section (or any other section that interests you:

http://www.cancer.gov/cancer_information/coping

The Cancer.net website, affiliated with ASCO, has a section on fatigue.

The NCCN(National Comprehensive Cancer Network) has recently published a 35 page document for a clinical practice guideline to Cancer-Related Fatigue. This document is in Adobe PDF format and can be downloaded and printed. Go to http://www.nccn.org/ and follow links to practice guidelines and supportive care.

A recent paper by Stasi R et al, Cancer-Related Fatigue, Cancer 2003;98:1786-801, is a review of the published literature on this subject. Some key points:

- In 50-75% of the cancer patients fatigue was reportedly present at diagnosis.

- While undergoing chemotherapy, cancer-related fatigue increased to 80-96%.

- For patients receiving radiotherapy, the increase was to 60-93%.

- Only two of the many things that have been tested for treating cancer-related fatigue were found to have a consistently positive effect: treatment of cancer-related anemia via erythropoietin agents and aerobic exercise (walking, bicycling, swimming.)  See this photo. 

One Patient's Experience

Other suggestions for reducing fatigue is the following as being tried by one hrpca patient (your physician needs to be involved in doing what this patient is doing):

I've been able to get a little improvement in my fatigue with a variety of things:

Glutamine -  up to 10g q.i.d	helps heal damaged, normal cells
Acetyl L-carnitine - 1000 mg b.i.d.	promotes cellular creation of energy. See below for the results of a study of using L-carnitine for fatigue.
Use of Procrit or Epo or Aranesp	Reduce or eliminate anemia
Drink plenty of water	staying hydrated
Effexor - about 10 mg b.i.d.	an antidepressant that palliates pain from PN. Keep depression in mind as something to prevent  and eliminate because it is the basis of qol.
Provigil - a drug for narcoleptics	I take a pill if I need to stay wide awake for an entire day; then it still lets me sleep.  (I don't use this much)
Sleep	I try to sleep all I can, and that is sometimes 12 hours a night.

Another single patient case study on reducing chemotherapy induced fatigue is a comparison of Modafinil and Methylphenidate.  This is new as of 6/24/04.

Depression and Fatigue

On the NCI coping website above, there is an article entitled, "Reducing Depression Does Not Reduce Fatigue".  To quote from that article, "Cancer patients often experience both depression and fatigue, and physicians have had good reason to think that relieving depression might also reduce fatigue. But a new large randomized trial has disproved that theory and shifted researchers' attention to other possible strategies to fight cancer-related fatigue."

L-Carnitine Deficiency May Cause Fatigue

A recent paper in Nutrition, reports on the use of L-Carnitine and its efficacy for fatigue, nutritional status, oxidative stress and related quality of life (1). The study only involved 12 patients(mixed group - not PCa specific), but the results may be of use in fighting fatigue and maintaining good nutritional status along with a better QOL. Patients were only slightly anemic (hemoglobin 10.9 g/dL) and hemoglobin levels did not change after treatment. The dose of L-Carnitine was  6 g/d for 4 weeks, orally administered.  All patients continued with their anti-cancer treatment during L-Carnitine supplementation.

They found that, "Nutritional variables (lean body mass and appetite) increased significantly after L-Carnitine supplementation. Levels of reactive oxygen species decreased and glutathione peroxidase increased but not significantly. Proinflammatory cytokines did not change significantly."  Thus, fatigue and QOL improvements are probably explained by the increase in lean body mass.  So fatigue may be a constituent of the cancer-related anorexia cachexia syndrome.

More recently, Cruciani RA, et al (2) reported on the results of a phase I/II trial with L-Carnitine supplementation. Patients with advanced cancer, carnitine deficiency (free carnitine <35 for males or <25 microM/L for females, or acyl/free carnitine ratio >0.4), moderate to severe fatigue, and a Karnofsky Performance Status score ≥50 were L-Carnitine at doses of 250-1500mg twice a day for 7 days.

Total carnitine levels in the intent to treat patients (27 patients) increased from 32.8 M/L to 54.3 M/L and free carnitine levels increased from 26.8 M/L to 44.1 M/L and fatigue decreased. The maximum dose achieved was 3000mg. No toxicities were noted.

A phase III trial is being run:

Phase III Randomized Study of Levocarnitine (L-carnitine) for the Management of Fatigue in Cancer Patients This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to gender, ECOG performance status (0-1 vs 2-3), and concurrent chemotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral levocarnitine (L-carnitine) twice daily on weeks 1-4.

Arm II: Patients receive oral placebo twice daily on weeks 1-4.

After week 4, all patients receive oral L-carnitine twice daily on weeks 5-8.

Fatigue is assessed at baseline and then at weeks 4 and 8.

The dose is not stated, but is most likely the 1500mg twice a day used in the phase I/II trials. The trial url is

http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=384087&version=HealthProfessional&protocolsearchid=2995098 and there are contact numbers at the bottom.

This might work IF you had a carnitine deficiency (< 35microM/L). Presumably you could see if you are deficient, take for 7 days and see if that raises the L-carnitine level and you feel less fatigued, otherwise, continue for another 7 days, etc. Or give it a try for a full 8 weeks per trial.

An Anecdotal Report from an HRPC Patient with Fatigue Who is trying L-Carnitine.

First, I have no idea whether my L-carnitine level is deficient. It has not been tested. I understand that I should measure out at 35 microM/L or more (normal for males). But, without knowing whether I'm deficient I nonetheless knew that my fatigue was moderate to severe causing involuntary laying around sleeping or doing nothing for 12 or 13 hours out of every 24. The rest of each day I was pretty doggone tired. The Phase 1 study described at www.hrpca.org/fatigue.html suggested that L- carnitine is pretty safe to take so I decided to have a go at it and talk to my onco later (next visit). I found it over the counter at my grocery store, 500mg, forty for $8.00. Last Thursday, Jan. 25, 2007, I took 1000mg in the a.m. and 1000mg in the p.m. Same dosage each day since, so, I've taken it for 5 days if we include today.

I also know that my hemoglobin for the last 3 months has been measuring 12.5 to 12.9 thus disqualifying me for an injection of aranesp. That drug has always helped with my fatigue but it is quite expensive so insurers like to see hemoglobin below 12 before paying.

Result: My L-carnitine supplementation has helped. Yesterday I had very little fatigue after 7 hours sleep the night before. Today I am experiencing very little fatigue after 7 hours sleep last night. No adverse side effects so far. I will take it for two more days and then stop until I see my onco on Feb. 8 when we will discuss.

I do not necessarily advocate trying things without first discussing with a doc and I am certainly not suggesting that now; however, I hope you and your doc can use my anecdotal success for discussion purposes. I'll tell you one thing for sure, my onco will have to forcibly argue me out of using L-carnitine; it sure helped me feel better.

Later he reports: I ended up taking it as described for a 7-day period then stopped until next appointment with my medical onco. That was a 7-day wait to see him. The fatigue began to return during the wait. On February 8 appointment I showed him the OTC bottle and we discussed taking it. He said go ahead and no need to test my carnitine level. I restarted it yesterday at 1000 mg in a.m. and 1000 mg in evening.

References for L-Carnitine

(1) Gramignano G., Lusso MR, Madeddu C, Massa E, Serpe R, Deiana L, Lamonica G, Dessi M, Spiga C, Astara G, Maccio A, Mantovani G, Efficacy of l-carnitine administration on fatigue, nutritional status, oxidative stress, and related quality of life in 12 advanced cancer patients undergoing anticancer therapy. Nutrition, 2006 Feb;22(2):136-45.

(2) Cruciani RA, Dvorkin E, Homel P, Malamud S, Culliney B, Lapin J, Portenoy RK, Esteban-Cruciani N., Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study, J Pain Symptom Manage. 2006 Dec;32(6):551-9.

Updated 2/13/2007 by Howard Hansen

American Ginseng Study on Cancer-Related Fatigue

Ginseng is often used by cancer patients and is a part of traditional Chinese medicine.  Known as an "adaptogen," it is said to help the body adapt to and overcome stress.  The possibility of having an anti-fatigue effect comes from preclinical studies and a 2003 ASCO meeting paper using Asian ginseng that suggested a benefit to cancer survivors.

Ginseng used: 4-year-old root American ginseng.

Doses studied: Three doses were used -- 750mg/day, 1000mg/day and 2000mg/day vs a placebo.  Dosing was twice a day for 8 weeks.

Number of patients: 282 with a variety of cancers with about half receiving chemotherapy, 69-72/arm.

Side Effects: There was no difference between the active and placebo groups in the rate of adverse effects reported or in the number withdrawing from the study due to adverse effects.

Results: This randomized pilot trial provided data to suggest that American Ginseng doses of 1000-2000 mg/d may be effective for alleviating cancer related fatigue: 25% of patients taking 1000 mg of ginseng and 27% of patients taking 2000 mg reported feeling "moderately better" or "much better," compared with only 10% of patients in both the placebo and the 750-mg-ginseng groups. At a press conference, the investigators indicated that, "there was not enough evidence yet to recommend the use of ginseng to patients; at present, evidence supports only exercise as an intervention that benefits fatigue...." They also cautioned that patients should make sure that their doctor(s) know they are taking this herb and to stop when starting therapy as just how the supplement might interact with treatment is unknown.

 
Reference on Ginseng

D. L. Barton, G. S. Soori, B. Bauer, J. Sloan, P. A. Johnson, C. Figueras, S. Duane, S. Dakhil, H. Liu, C. L. Loprinzi, A pilot, multi-dose, placebo-controlled evaluation of american ginseng (panax quinquefolius) to improve cancer-related fatigue: NCCTG trial N03CA, Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 9001.

H. Hansen 7/26/07.

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Excerpt from "Choices: Living with Cancer, Dying with Dignity" on Fatigue

INTRODUCTION

You may notice that even on a relaxing day, you become very tired in the afternoon. Or you may find that you cannot finish projects because you are suddenly overwhelmed by fatigue. You may be unable to keep your eyes open or feel as if you cannot move out of your chair. Tasks that were once simple may seem too complicated to understand. All of these symptoms can be attributed to fatigue.

While sleepiness may be caused by pain medication—especially when taking a new prescription or dosage—fatigue is usually not caused by medication. If pain medicine is in the right dose, you will probably feel more energized, not less, because you are sleeping better and not worn out by the pain itself.

Fatigue is caused by the cancer. In a process not fully understood by medical science, the cancer cells release toxins. Like any toxic substance, these cytotoxins weaken your system. As your body attempts to fights the foreign materials released by the cancer cells, you become tired and feverish, just as you do when fighting any illness. The liver and the kidneys may be strained and begin to fail.

As mentioned in the section "Low Blood Counts," the number one cause of fatigue is impairment of the bone marrow and its inability to produce enough red blood cells to provide your body with the oxygen it needs.

PALLIATIVE MEASURES

Depending on the cause of the fatigue, blood transfusions or changes in medication or the use of oxygen may help. So, too, may changes in lifestyle.

LIFESTYLE CONSIDERATIONS

Fatigue is one of the most insidious and most irritating symptoms of cancer’s progress. It can come upon you suddenly, giving you the feeling that all the energy has drained out of your body and you cannot move another step. You may find yourself panting after one flight of stairs. Or you may simply take less pleasure in events and people because you are tired.

Most devastating to self-esteem and relationships is mental fatigue. When the body’s resources are strained, the body focuses its energy on essential physical systems. Mental processes shut down. Balancing the checkbook as you usually do suddenly may seem confusing. Planning your daily schedule may be overwhelming. Easy questions may evoke a sharp response because you don’t understand what is being asked. You simply can’t process information as well as you usually do, no matter how hard you try.

Mental fatigue is disruptive because, at first, neither you nor your family may realize what is happening. You may seem cranky or uncooperative rather than tired. Be aware that you may be experiencing severe fatigue. The awareness can help both you and your family avoid stress.

For example, if you are having trouble with the checkbook or a legal document or following a story, take time out. Rest or sleep, then try again. Do important work when you are at your best. For some, that is in the morning; for others, it may be later in the day or after a nap.

You and your family need to look out for signs that you need rest, such as body language or lessened ability to participate in conversations. Learning to recognize the signs will help you stop before you become over-tired, and before you and your family make decisions based on frustration rather than careful consideration of the facts and options.

To accommodate fatigue, you may need to work fewer hours each day; you will certainly have to pace your activities. Busy days, whether family gathering or trips to the medical center, may need to be followed by days of rest.

You may need to set aside time each day for rest.

Scheduling of activities will become important in order to avoid planning too many things on one day. If you plan to go to work in the afternoon, you probably should not do household chores in the morning.

One way to save energy is to ask that friends come to you rather than traveling to their house. Instead of preparing dinner, you may want to meet at a nearby restaurant, order a pizza or ask your visitors to bring food.

Remember that as you do less, your caregiver must do more. His or her fatigue must also be considered in your schedule. Set aside time for your caregiver to relax. Find ways to lessen the energy required for everyone’s chores. This may mean asking someone to help with cleaning or yard work, or it may simply mean that your approach tasks creatively.

Find ways to conserve energy. Instead of carrying your baggage onto the plane, check it at the curb. Get a handicapped parking tag so you can shorten the walk to the theater, the mall or business appointments. Use a wheelchair to tour the museum instead of walking.

Each of these changes in the way you do things represents a choice. You may choose to tour part of an exhibit on your feet rather than see everything from a wheelchair. It is important, however, for your to realize that you have choices. "Reduced energy" is not the same as "no energy;" changing how you do things is not the same as giving up the activities that give you pleasure.

Most cancer centers have pamphlets about fatigue because this is a side effect of many treatments as well as a symptom that the cancer is spreading.

PUBLIC IMAGE

Many of the suggestions for dealing with fatigue represent a public, although unspoken, statement that you’re "less able" than you were before. It is hard psychologically to sit in a wheelchair when you have been active. Letting someone do your chores or having your work taken over by co-workers is hard to accept. Talk to your doctor, your family, the cancer center social works and other patients about these losses and the options you have.

Molly Sower Sugarman

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