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Alert Number 108

Fludarabine Therapy Increases Risk of Skin Cancer

Date: July 19, 2005

This latest article (abstract below) should come as no surprise to you, if you have been following our discussion thread linking fludarabine therapy with deep immune suppression, and the resulting window of opportunity for serious infections and secondary cancers. To recap:

  1. Fludarabine therapy kills T-cells as well as B-cells. This is also true of Campath therapy, or high dose steroid therapy with drugs such as prednisone.
  2. Loss of B-cells, T-cells and very often sharply reduced levels of neutrophils adds up to deep and sometimes long lasting suppression of the immune system.
  3. Our bodies are constantly under attack, both by external invaders (bacteria, viruses, fungi) and home grown variety of malcontents, such as tiny colonies of pre-cancer cells. From the day we are born to the day we die, there is an on-going battle between our immune systems and these threats to our very lives.
  4. Most often, even in obviously "healthy" people, there is at best a stalemate. Many of the viruses such as Herpes (shingles), human papilloma virus (warts, genital cancers), cytomegalovirus, Epstein Barr virus (Mono, lymphoma), even TB bacillus are not completely eradicated. Small colonies of them survive in our bodies, waiting to pounce during a window of vulnerability when the immune system is not firing on all cylinders.
  5. Most of us who have been careless about sun exposure have small and unnoticed colonies of cells that have been damaged due to UV radiation. These pose little problem to people with functioning immune systems, the constant surveillance of our immune system cells quickly takes care of these pre-malignant cells, most of the time, keeping them from becoming a real problem later on.
  6. Not so for folks with deep and too long suppression of their immune systems due to therapy with drugs such as fludarabine, Campath. Chances are much higher that the unnoticed little rough patch of skin on your scalp uses this opportunity to blossom into full blown skin cancer.
  7. No big deal, you say? Hardly. Squamous cell carcinoma and basal cell carcinoma can become very serious, even life threatening co-morbidities in CLL patients.

You may not always have a choice about avoiding immune suppressive drugs. What should you do? Try and protect yourself against potential problems down the road by taking sensible precautions.

  1. Be extra prudent about sun exposure. And discuss with your doctor the need for vitamin D3 supplements, this vitamin is very important for general good health, and under normal circumstances our bodies make it upon exposure to UV in sunlight. But these are hardly normal circumstances, you have CLL. Right?
  2. Ask your doctor about protective measures against Herpes ahead of the fludarabine therapy. Shingles can be very painful, and I know of one patient who became blind as a result of shingles outbreak in both his eyes. The Mayo best practices we reviewed in an earlier article mandates pre-treatment with Famvir (or similar anti-viral) as protection against Herpes virus. Ask us about getting hold of the full text of this expert article, if you need it to convince your local guy.
  3. Campath therapy now requires standard medication to protect against CMV reactivation. If you have had exposure to hepatitis, TB and the like in your earlier life, it is important that you bring this to the attention of your oncologist.
  4. It really helps if you do not have an active infection going into chemotherapy with immune suppressive drugs.

Information is power. Below are a bunch of links to help you get started.

What You and Your Oncologist Need to Know about CLL
Fludarabine Monotherapy No Longer the Gold Standard
Dying to Get a Tan?
Vitamin D3 Essential for Health
Viral Drivers
Are We There Yet?

Be well,



Leuk Lymphoma. 2005 Jul;46(7):1051-5.

Accelerated growth of skin carcinoma following fludarabine therapy for chronic lymphocytic leukemia.

Rashid K, Ng R, Mastan A, Sager D, Hirschman R.

We present four patients with chronic lymphocytic leukemia treated with fludarabine, who developed aggressive skin cancer after years of quiescence, a short time after institution of treatment. Their leukemias responded well to therapy with fludarabine with initial treatment as well as relapse. Three patients had recurrence with basal cell carcinomas with multiple, rapidly growing tumors and one had recurrence of both basal and squamous cancers and eventually died of metastatic squamous cell carcinoma. Fludarabine induces prolonged period of lymphopenia, affecting especially the T cell population, which is crucial in the defense against skin cancers. There appears to be a direct association between fludarabine and the flare up of skin cancers in these patients, possibly analogous to the increased incidence of these malignancies in patients on chronic cyclosporine immunosuppression.

PMID: 16019557

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