The War on Cancer

Townsend Letter for Doctors and Patients,  August, 2001  by Ralph W. Moss

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Glee Over Gleevec

Each year, 26,000 of the world's oncologists parade their accomplishments at the annual meeting of the American Society of Clinical Oncology (ASCO). In May, the media was filled with reports of the impending conquest of cancer. This happens every year, but this year's mania exceeded all others. The front cover of Barron's screamed, "Investing in Health: Curing Cancer." The article stated baldly: "We are finally winning the war." The business weekly predicted that, for our children, cancer will be just another ho-hum disease, for which they will "pop a few pills every day." The New York Times announced "the long-awaited payoff from decades of research into the molecular biology of cancer. Unlike chemotherapy and radiation... the new agents are designed to kill cancer cells alone. In principle, they should eliminate malignancies more effectively while being far gentler on the patient."

An oncologist at the University of Arizona told reporters that in 20 years "he might just be out of a job." But it was Time magazine (May 28, 2001) that went over the top. Its cover read, "There is new ammunition in the war against cancer... .Is this the breakthrough we've been waiting for?" The word "CANCER" was two inches high. This message of cure was carried to the farthest corners of the globe. An elderly relative of mine, who is not sure who is president of the United States, had heard about the cancer cure.

So, is the end in sight? To answer this, we need to examine Gleevec, the drug that triggered the hysteria. In May, Gleevec was approved by the FDA as a treatment for chronic myelogenous leukemia (CML). Time's sources call it "a magic pill...a miracle...a breakthrough." CML affects 4,500 Americans per year, about 0.3 percent of the 1.2 million new US cancer patients. The treatment is logical. Since 1960, it has been known that CML patients have a small "Philadelphia chromosome" that is not found in other people, including other cancer patients. This provides a unique molecular target for a new drug. However, this clear-cut target is lacking for most other cancers.

Surprisingly, Gleevec was not tested in randomized controlled trials (RCTs) before being approved by the FDA. In the results of a small test reported in the New England Journal of Medicine, Gleevec did restore normal blood counts in 53 out of 54 interferon-resistant CML patients (2001;344:1031-7). But whether or not Gleevec positively affects long-term survival is still not known. As Richard Klausner MD, director of the National Cancer Institute, has correctly said, "It is still unclear for how long Gleevec will control CML. Nor is it known if the drug actually cures CML patients or delays the onset of more advanced forms of the cancer."

Another use for Gleevec might be in the treatment of gastrointestinal stromal tumor (GIST), which also affects about 5,000 Americans annually. With daily Gleevec treatment, for up to three months, there were partial responses in 54% of GIST patients. The disease stabilized in 34% of patients. However, these patients have only been studied for a few months.

Now that Gleevec has been approved, people with other kinds of cancer are demanding this "miracle drug." Prescribing Gleevec for other tumors may be "irresponsible," to quote researcher Allan van Oosterom, but try and stop patients from getting it! Not surprisingly, this "miracle" comes at a high price: Novartis is charging $2,400 per month, or almost $30,000 per year. And patients may need to continue taking it for life.

Is the tentative success of Gleevec the "proof of principle" that similar drugs will work in more common forms of cancers? I don't think so. Most of the other new drugs do not have such clear-cut molecular targets. In fact, for most anticancer drugs, the preliminary clinical evidence is not very encouraging.

Fate of Endostatin

It is instructive to look at Endostatin, a much-touted anti-angiogenesis treatment. Just three years ago, the New York Times touted Endostatin as a virtual cure of cancer. But at the 2001 ASCO meeting, scientists from M.D. Anderson Cancer Center reported the results of a phase I clinical trial. Of 22 patients, only one showed any evidence of anti-tumor activity; a second patient was celebrated just for remaining in the study for one year.

Time assembled ten other alleged miracle drugs. The list includes AstraZeneca's Iressa. At the company's website, Iressa is described as "exciting," "novel" and a "breakthrough." The drug "has shrunk tumors in phase I trials in patients who have failed multiple lines of chemotherapy," they say. And this is technically true, since there was a partial response in two patients, one with non-small cell lung cancer (NSCLC), the other with prostate cancer. The overall partial response rate was 1.5 percent (Proc ASCO 2000 #686). Undeterred, company spokespersons classify this as "encouraging anti-tumor activity in a selected range of tumor types." At this year's ASCO meeting, one small Japanese trial showed 5 out of 23 partial responses in lung cancer (ASCO 2001 #1292). Nor is Iressa entirely nontoxic: there were "skin changes" in 58%, diarrhea in 33%, nausea in 25% and vomiting in 22% of patients. Four patients had to withdraw because of toxicity.