Good, Better and Best?

Last week, the medical journal The Lancet published the results of a clinical trial that compared three chemotherapy treatments for metastatic (stage IV) colon and rectal cancer. The journal's editors characterized these three forms of chemotherapy as "Good, Better, Best," and stated that "many efficacious chemotherapy regimens are available for the treatment of colorectal cancer." To put it mildly, I think this is an exaggeration of the benefit of chemotherapy for advanced cancer of the colon and rectum.

According to the data, the average survival of patients in this study ranged from 266 days for the "good" therapy to 302 days for the "best" therapy. Taken as a whole, the average survival was around 10 months. However, this only tells part of the story.

The so-called "good" treatment (a new drug called raltitrexed) turned out to be no more effective, but quite a bit more toxic, than the "better" and "best" regimens. Many patients taking raltitrexed developed severe diarrhea, nausea, and vomiting, as well as rampant destruction of their bone marrow. Raltitrexed was so toxic that eighteen patients (about 6 percent) died from its adverse effects!

The other two treatments, which had about equal effects on survival, were based on the drug 5-FU. The de Gramont regimen consisted of folinic acid plus a single big dose of 5-FU followed by an infusion of 5-FU. The Lokich regimen consisted of a protracted infusion of 5-FU. The authors of the study called the Lokich continuous infusion of 5-FU "an excellent alternative regimen," although it brought toxic effects of its own, such as more infections and blood clots.

The purpose of giving 5-FU is said to be "palliation." This is defined by the authors as the "improvement, control, and prevention of symptoms." But palliation of symptoms is only one aspect of quality of life for cancer patients. Does 5-FU, as a palliative therapy, really contribute to an improved quality of life or greater sense of well-being? Many patients had to stop treatment prematurely because of its toxicity. And while about half the patients reported a decrease in symptoms such as fatigue, pain, insomnia and appetite loss, nearly 75 percent reported moderate or severe toxic effects, including an increase in nausea and vomiting, constipation, diarrhea, dry and sore mouth, eating problems, and pain in the hands and feet.

In a previous analysis of 13 trials of palliative chemotherapy for advanced colorectal cancer, the average (median) survival was 11.7 months with chemotherapy compared to 8.0 months without. Thus, chemotherapy extended survival by 3.7 months. An unresolved issue is that these studies compared patients who received active treatment with those who simply got supportive care. "Supportive care" sounds humane, but in actuality these patients were told that they would be offered no further anticancer treatments. Those in the chemotherapy group at least received hope in the form of active treatment.

Could this make a difference in survival? I believe so. "People's perceptions of their treatment play an important role in healing," according to Professor Daniel E. Moerman of the University of Michigan-Dearborn. Any treatment works better when both physician and patient believe in it. To deprive patients of all hope could certainly act as a "nocebo" (a negative placebo) and have damaging effects on psychosocial well-being. As an Oslo study has shown, psychosocial well-being is an important predictor of survival for some cancer patients.

It is true that some new drugs, such as CPT-11, have been introduced to treat advanced colorectal cancer. But 5-FU is still the standby. I find it dismaying that a drug that was already old hat when the "War on Cancer" was launched in 1971 is still the best that the oncology community can come up with. Isn't it time that they broke out of the chemotherapy model and looked at more promising treatments in the realm of complementary and alternative medicine?

Here at the Moss Reports

There will not be a newsletter next week, as I am going to Orlando, Florida, for the American Society of Clinical Oncology (ASCO) meeting. I hope to bring back news of exciting treatments emerging from cancer clinics and laboratories around the world. See you in two weeks.

--Ralph W. Moss, Ph.D.

Sources:

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Christensen D. Medical mimicry. Science News 2001;159:5.
http://www.sciencenews.org/20010203/bob9.asp

Good, better, best (Talking Points). Lancet 2002;359:1533.

McKenna DJ et al. Black cohosh: efficacy, safety, and use in clinical and preclinical applications. Altern Ther Health Med 2001;7:93-100

Kaasa S and Mastekaasa A. Psychosocial well-being of patients with inoperable non-small cell lung cancer. The importance of treatment- and disease-related factors. Acta Oncol 1988;27:829-35.

Kaasa S et al. Prognostic factors for patients with inoperable non-small cell lung cancer, limited disease. The importance of patients' subjective experience of disease and psychosocial well-being. Radiother Oncol 1989;15:235-42.

Maughan TS et al. Comparison of survival, palliation, and quality of life with three chemotherapy regimens in metastatic colorectal cancer: a multicentre randomised trial. Lancet 2002;359;1555-63.

Simmonds PC. Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. BMJ 2000;321:531-5.