Where to Go - A Survey of WorldWide CAM Cancer Resources

This week, we here at cancerdecisions.com are launching one of our most ambitious projects ever. Our Where To Go? series will be a regional survey of medical resources for cancer patients who are looking for the best cancer care, including complementary and alternative medicine (CAM) options.

Over the course of the coming months I intend to visit a geographically diverse selection of doctors and clinics in order eventually to assemble a comprehensive region-by-region CAM resource guide. Some people are looking for the best treatment opportunities within driving distance of their own homes. Others are ready and willing to range further afield in their search for innovative treatments. Either way, this series is intended to provide cancer patients with a means to identify the CAM providers and treatment options that are most appropriate for their own circumstances.

I have of course traveled many times in search of innovative cancer treatments, but the aim of this series is quite different from those earlier expeditions. This time, I am methodically trying to track down exactly what is available in any particular locale. Overall, the series will be descriptive, rather than prescriptive: armed with the facts and impressions that I provide, cancer patients can then weigh their options and make choices based on a comprehensive overview of what is available. For those who still need help, there are of course the comprehensive diagnosis-specific Moss Reports as well as my phone consultation service.

We have chosen to launch the Where To Go? series this week with a report on the CAM cancer resources in Houston, Texas, which I visited in April of this year. Houston is a major medical destination, not just for Americans but for people from many other countries. In this report I discuss M. D. Anderson Cancer Center, which, according to US News and World Report, is America's top rated cancer center. I also discuss what is arguably Houston's number one alternative cancer treatment destination, and examine a little known program utilizing whole body hyperthermia (heat treatment) in an academic setting.

In May I will be reporting on Philadelphia, home to five medical schools, and certainly one of America's most famous centers of medical excellence.

This will be followed in June or July by a report on my upcoming trip to Germany, where I will visit a dozen clinics and laboratories that are pursuing a CAM approach to cancer. (This is my sixth such site visit to Germany in the past decade.)

Reports on the Chicago region, New York, New England, Southern California, Nevada, Arizona, and Florida are all in the pipeline for the coming year.

I am open to readers' suggestions concerning doctors, clinics and hospitals that you feel are treating cancer in a particularly innovative way. Please send your suggestions to This e-mail address is being protected from spam bots, you need JavaScript enabled to view it . Unfortunately, due to the volume of email we receive it may not be possible for me to reply in detail to your message. But be assured that I will read all your suggestions and consider them carefully in arranging future site visits.

To order Where To Go? - Houston, TX please click here.

Cancer Drug Trials: Quitting While You're Ahead - Part II

When clinical trials of new cancer drugs are halted early because of a positive response trend in those receiving the new drug, the early stoppage is generally heralded as an example of progress, a welcome glimmer of hope. But there is also a potential downside to stopping clinical trials early which is often overlooked. Last week we began a two-part discussion of the implications of early trial stoppage. This week we conclude that discussion, with references.

In fairness, when the sponsors and investigators who design a particular research protocol build in a clause (as they often do) that explicitly demands early stoppage if a favorable trend emerges within a given period of time, data monitoring committees have no choice but to halt a trial early. Nevertheless, the immediate result of early stoppage is typically a rush to favorable judgment.

Early termination of a clinical trial is intended to ensure that the participants who are receiving the standard treatment can immediately be offered the new and apparently more effective drug. But this decision then cuts off the possibility that the new drug might ultimately turn out to be ineffective, or perhaps even harmful, if the trial were allowed to proceed to term. The decision to halt the trial early could then prove dangerous for the many thousands of patients who will receive the new drug if it is approved on the basis of an early favorable trend. In effect, it makes the public unwitting participants in a vast, unofficial "clinical trial" whose purpose is essentially to determine whether drugs that have been granted premature approval are indeed safe and effective over time.

Defenders of the system claim that new cancer drugs are indeed continually monitored after they are approved. Companies are supposed to track reports of adverse effects from their products and make occasional safety reports. In the US, companies receiving accelerated approval for their drugs (and this includes many of the top selling new agents) are supposed to carry out post-marketing surveillance trials, sometimes called phase IV studies. These studies are meant to assess the actual value of the new drugs in the real-world clinical setting, and involve safety surveillance (so-called pharmacovigilance) and ongoing evaluations of the effectiveness of the drugs. When phase IV studies are carried out they may indeed detect serious problems with the agents, as has happened with cerivastatin (brand names Baycol and Lipobay), troglitazone (Rezulin) and rofecoxib (Vioxx). But, in cancer, these phase IV trials are often not completed and FDA has been lax in enforcing such regulations.

However, until recently, the funding and enforcement of this kind of post-approval monitoring has been woefully inadequate. For example, study by Duke University researchers showed that in 2003, the top 20 pharmaceutical manufacturers spent 0.3 percent of sales on drug safety monitoring following FDA approval, while in the same year they spent 15.6 percent of sales on research and development of new drugs. (It should be pointed out that this study was itself funded by the pharmaceutical industry - i.e., even the drug industry admits that resources for post-approval monitoring are inadequate.) The researchers also found that the Office of Drug Safety in the FDA's Center for Drug Evaluation and Research spends less each year on post-approval monitoring than the mean safety spending by an individual firm (Ridley, 2006).

Post-market safety monitoring is therefore acknowledged to be inadequate and efforts are underway to improve it. However, even less emphasis is placed on the fact that some of these prematurely approved drugs are actually ineffective, and may not really benefiting patients in any substantive way.

"At the time when marketing authorizations are granted, we are aware that we don't know everything about the medicine," said Monika Bernstetter a spokeswoman for the European Medicines Agency, the European equivalent of the US Food and Drug Administration. "In the end, this is an ongoing process and it is an issue of risk management."

In 2006, the FDA itself reported that most post-marketing studies that drug companies promised to conduct on approved medications remained uncompleted. According to the report, which appeared on the FDA Web site, 797, or 65 percent, of 1,231 post-market studies on new medications were listed as "pending" and had not begun as of Sept. 30, 2006, and 28 additional studies were listed as "delayed." An additional 231 studies, or 19 percent, were listed as "ongoing." In fact, pharmaceutical companies had only submitted 172 such studies, or 14 percent, to FDA. In most cases, the report said, FDA does not have the authority to require pharmaceutical companies to complete post-market studies. Sens. Chuck Grassley (R-Iowa) and Christopher Dodd (D-Conn.) have introduced a bipartisan bill that would provide FDA with more authority to require pharmaceutical and medical device companies to complete the post-market studies (Corbett Dooren, Wall Street Journal, March 3, 2007).

Grassley in particular has been on a crusade since 2004 to improve post-market surveillance of approved drugs. In response to his initiatives in February 2008 the FDA has launched its so-called "Safety First" campaign. But on March 13, 2008, Grassley issued a press release in which he said that he was concerned that the Safety First initiative may not get at the problem with post-market surveillance by the FDA.

"The office in charge of approving drugs in the first place is allowed to have power over the office that specializes in what happens with drugs after they've been on the market for awhile," the Senator said. "This structure creates a conflict where the pride that goes with having approved a drug can get in the way of an objective review of whether a drug is turning out to be as safe and effective as it ought to be, and there's no evidence that this structure has changed with the 'Safety First' initiative" (Grassley 2008).

This has profound implications for cancer patients who are trying to decide whether or not to take a particular medicine. The good publicity surrounding newly approved agents may stampede patients into taking a new drug. But they may not be getting a true picture of the safety and effectiveness of such agents, especially when trials are terminated prematurely.

"Just having preliminary promising results is not good enough," Dr. Apolone of the Mario Negri Institute said. He told the Associated Press that it could take years to discover the long-term benefits or side effects of new drugs, yet most studies only last about two years. When tests are interrupted at the halfway point, the smaller numbers may exaggerate a drug's benefits.

"There's great pressure on the cancer community to get new drugs out as soon as possible," according to David Kerr, MD, editor in chief of Annals of Oncology, which published the Mario Negri study. Kerr, a professor of oncology at Oxford University, said that the trend of stopping trials early was worrying. "Everyone wants new and powerful therapies available quickly," he said. "But we need to be sure we understand the evidence first."

The Mario Negri Institute, founded in 1961, has emerged as an important center for the objective evaluation of claims made for new cancer drugs. For instance, last year they published a study showing that two-thirds of drugs approved for leukemia and lymphoma did not demonstrate proof of added value over established drugs, mainly due to faulty study design (Bertele 2007).

--Ralph W. Moss, Ph.D.

References:

Bertele V, Banzi R, Capasso F, et al. Haematological anticancer drugs in Europe: any added value at the time of approval? Eur J Clin Pharmacol. 2007;63:713-719.

Grassley, Chuck. Grassley says changes to improve FDA post-market review remain elusive. Press release. March 13th, 2008. Available at Web site: http://grassley.senate.gov

Laurance, Jeremy. Scientists attack 'breakthrough' cancer drugs. The Independent. April 9, 2008.

Ridley D, Kramer J, Tilson H, et al. Spending on post-approval drug safety. Health Affairs (Milwood). 2006; 25(2):429-36

Trotta F, Apolone G, Garattini S, et al. Stopping a trial early in oncology: for patients or for industry? Ann. Oncol. 2008, Apr. 9