Cancer Decisions - Free Newsletter -June 27, 2004

THE MOSS REPORTS

"The great tragedy of Science," wrote the celebrated nineteenth century British biologist Thomas Huxley, "is the slaying of a beautiful hypothesis by an ugly fact."

The hypothesis underpinning so-called targeted cancer treatments is indeed beautiful. These treatments are designed to interfere on a molecular level with the specific metabolic processes within cancer cells that enable tumors to grow and multiply with such devastating speed. Better yet, these treatments are designed to be selective, targeting only cancer cells and leaving normal cells largely unharmed.

However, the ugly fact is that these treatments are no magic wand. Used on their own they make little or no impact on the disease. Their effect is typically only felt when they are used in combination with chemotherapy, and even then the difference they make is extremely modest.

Yet to judge by the mounting media excitement concerning targeted cancer treatments, a cure for this dread disease is almost within our grasp.

How are cancer patients to assess the real worth of treatments that are announced with such triumphalism in the media, yet which, in the real world of cancer therapy, are actually making only the most modest of differences, if any?

For the past thirty years I have been studying and closely monitoring developments within the field of cancer treatment, sorting fact from fiction, and helping cancer patients and their families to understand and weigh the usefulness of the treatments they have been offered.

The Moss Reports represent a comprehensive library of cancer guides. In them, my years of experience in researching cancer treatments have been distilled into a careful assessment of the worth and effectiveness of the conventional and alternative treatments of over two hundred different kinds of cancer.

If you or someone you love has received a diagnosis of cancer, a Moss Report can provide you with the key to understanding the best that conventional and alternative medicine have to offer. You can order a Moss Report on your specific cancer type by calling Diane at 1-800-980-1234 (814-238-3367 from outside the US), or by visiting our website: http://www.cancerdecisions.com

We look forward to helping you.

TARCEVA TOUTED FOR LUNG CANCER

At its clinical trials web page, the National Cancer Institute announces the results of a Phase III trial with the celebratory headline: "Erlotinib (Tarceva®) extends survival in advanced lung cancer."

The study's principal investigator, Dr. Frances Shepherd of the University of Toronto, asserts that patients with advanced non-small cell lung cancer "now have an option to improve survival with minimal toxicity."

"This is a landmark study since it is the first to document a survival advantage," Dr. Shepherd says. The results are particularly compelling, she adds, because "until now there has been no treatment option for these patients."

News of this triumphant announcement quickly echoed around the world. But what does the data from this study really show?

Median survival in the Tarceva-treated patients was 6.7 months compared with 4.7 months for patients in the placebo group; i.e., the actual gain in survival was two months. The time to pain progression was 2.79 months in the Tarceva-treated group vs. 1.91 months in the placebo group, a gain of about three weeks. And progression-free survival, which some consider the most important measure of a drug's benefit, averaged 2.23 months in the Tarceva-treated group vs. 1.84 months in the placebo group, amounting to a gain of just 12 days.

In essence, the results of this study translate into this: patients who take Tarceva will discover, on average, that their tumors have progressed two weeks later than the tumors of patients who do not take this drug. Tarceva-takers will then suffer a somewhat slower decline and will die two months later than patients who don't take the drug.

The media, grasping at any positive news about cancer, was predictably enthusiastic about Tarceva's performance after these clinical trial results were announced at the American Society for Clinical Oncology's annual meeting in June (Abstract #7022).

I located 140 news articles about this ASCO paper. Here are some typical headlines:

Drug improves survival in lung cancer patients (USA Today, June 5, 2004)
Cancer drug prolongs survival (Newsday, NY, June 5, 2004)
Trials show chemotherapy helping after lung surgery (New York Times, NY - June 5, 2004)
New 'smart bomb' cancer drugs show promise (Palm Beach Post, FL, June 5, 2004)
Treatments boost lung cancer survival (MSNBC, June 5, 2004)
'Targeted therapies' tackle cancers (Pioneer Press, MN, June 6, 2004
Cancer drug prolongs life in study (Los Angeles Times, June 6, 2004)

Over 400 websites now refer to Tarceva as ‘a breakthrough drug'. But not everyone agrees. Marianna Koczywas, MD, a medical oncologist at City of Hope National Medical Center in Duarte, California, told a reporter from the Medscape website that the Tarceva results were simply not compelling. While a two-month increase in survival is statistically significant, she said, it is still a small benefit and she is not convinced that it will have any impact on clinical management. "The improvement in quality of life is more compelling," she conceded, although, as the clinical trial showed, pain relief only amounted to three weeks of benefit (Peck 2004). In other words, Tarceva is clearly not a cure. Nor is it without side effects of its own, the most common of which are extensive skin rash and diarrhea.

Economic Dimensions

Dr. Koczywas added that the current study may speed approval of the drug (Peck 2004). That is what investors are betting on, as Wall Street went wild over the news. In the wake of what TheStreet.com called "a triumphant clinical announcement," the shares of OSI Pharmaceuticals soared. The value of shares in OSI's Tarceva partners, Genentech and Swiss drugmaker Roche, also skyrocketed. According to TheStreet.com, for Genentech, "Tarceva's success is like hitting the cancer-drug lottery jackpot twice." Last year, in a similar scenario, Genentech also "hit it big with positive results from its Avastin colon cancer study" (Feuerstein 2004).

Click on or go the link below for my 2003 article on Avastin:
http://www.cancerdecisions.com/062903_page.html

If the FDA grants Tarceva a priority review, as now seems likely, it could be on the market in the first quarter of 2005. How much will that be worth to OSI and its shareholders? There are at least 100,000 non-small cell lung cancer (NSCLC) patients in the US alone who might use the product. Banc [sic] of America Securities biotech analyst Mike King puts a $30,000 per patient price tag on the drug. If patients survive about six months, as anticipated, then Tarceva could have annual sales of around $1.5 billion. But Tarceva will have to compete with AstraZeneca's relatively new lung cancer drug, Iressa. Other estimates put the drug's sales potential at a more modest $500 million to $700 million per year.

Targeted Drugs

Everyone in authority is now touting targeted drugs such as Tarceva, Iressa and Avastin as the great hope in cancer, the culmination of decades of hard work and inspiration. But the clinical track record so far has not lived up to the hype. I realize that Tarceva is being tried in very ill patients with advanced or treatment-resistant cancers, and that it might produce better results in earlier stages of the disease, especially when used as an adjuvant after conventional chemotherapy. But even so, the results do not look very promising to me. The results with Tarceva are similar to those with other targeted drugs—a few months increased survival, at best. We continue to hear claims that these agents are revolutionizing cancer care. But if a few months' extra survival is the best they can do, even when used in conjunction with powerful and intensive chemotherapy, I simply don't see what all the shouting is about.

Comparison to Melatonin

I must admit to a considerable degree of frustration as I contemplate the overheated and uncritical publicity about Tarceva. I cannot help wondering how well this drug would do if it were put up against some well-known complementary and alternative (CAM) treatments. To take just one example out of many, Paolo Lissoni, MD, and his colleagues at the New St. Gerardo Hospital of Monza, Italy (north of Milan) have repeatedly shown in clinical trials that the hormone melatonin, when added to chemotherapy, significantly increases survival and has other benefits in terms of quality of life. In one study of non-small cell lung cancer, the tumor response rate was nearly double in patients who received added melatonin (11 out of 34) as compared to those who didn't (6 out of 35). The percentage of one-year survival was significantly higher in patients treated with melatonin plus chemotherapy than in those who received chemotherapy alone (15 out of 34 vs. 7 out of 36) (Lissoni 1992).

Dr. Lissoni has published literally dozens of PubMed-listed articles on the topic of melatonin and cancer, and has presented his findings at ASCO in past years. I cite nine randomized clinical trial articles in the references below. When I visited Dr. Lissoni in Monza last November I found a brilliant man who was all but worn out by his decades-long struggle to gain acceptance for this simple and well-documented therapy.

Click on or go to the link below for an abstract of my recent medical journal article on Dr. Lissoni and other Italian CAM therapies:
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15165505

So what is the difference between Tarceva and melatonin?

For one thing, patients seem to do better with added melatonin than they do with Tarceva. Melatonin also has a very low toxicity profile. Melatonin is a naturally-occurring compound that has long been in the public domain. As an adjuvant cancer treatment it is usually taken in a relatively high doses of 20 milligrams per day. (NOTE: Do not attempt this treatment except under the care of a qualified physician.) Furthermore, it is a great deal cheaper than Tarceva. The cost of 20 milligrams of melatonin averages approximately 40 cents per day. Over a six month period a patient would spend a total of $75 on this supplement. By contrast, the cost of Tarceva given over the same period would be around $30,000. Thus, melatonin could theoretically save US $29,925 in medical costs over a six-month period.

Tarceva praised to the skies; melatonin all but ignored. Call me cynical, but I believe that the media, Wall Street and a few celebrated professors have gone wild over Tarceva not so much because of its therapeutic value but because of its positive impact on the stock market's bottom line.

--Ralph W. Moss, Ph.D.

REFERENCES:

Feuerstein, Adam. Successful Tarceva study sends shares skyward TheStreet.com. April 26, 2004. Accessed June 9, 2004 from:
http://www.thestreet.com/tech/adamfeuerstein/10156368.html

Ghielmini M, Pagani O, de Jong J, Pampallona S, Conti A, Maestroni G, Sessa C, Cavalli F. Double-blind randomized study on the myeloprotective effect of melatonin in combination with carboplatin and etoposide in advanced lung cancer. Br J Cancer. 1999 Jun;80(7):1058-61.

Lissoni P, Chilelli M, Villa S, Cerizza L, Tancini G. Five year survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial. J Pineal Res. 2003 Aug;35(1):12-5.

Lissoni P, Malugani F, Bukovec R, Bordin V, Perego M, Mengo S, Ardizzoia A, Tancini G. Reduction of cisplatin-induced anemia by the pineal indole 5-methoxytryptamine in metastatic lung cancer patients. Neuroendocrinol Lett. 2003 Feb-Apr;24(1-2):83-5.

Lissoni P, Barni S, Mandala M, Ardizzoia A, Paolorossi F, Vaghi M, Longarini R, Malugani F, Tancini G. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer. 1999 Nov;35(12):1688-92.

Lissoni P, Paolorossi F, Ardizzoia A, Barni S, Chilelli M, Mancuso M, Tancini G, Conti A, Maestroni GJ. A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. J Pineal Res. 1997 Aug;23(1):15-9.

Lissoni P, Tancini G, Barni S, Paolorossi F, Ardizzoia A, Conti A, Maestroni G. Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin. Support Care Cancer. 1997 Mar;5(2):126-9.

Lissoni P, Meregalli S, Fossati V, Paolorossi F, Barni S, Tancini G, Frigerio F. A randomized study of immunotherapy with low-dose subcutaneous interleukin-2 plus melatonin vs chemotherapy with cisplatin and etoposide as first-line therapy for advanced non-small cell lung cancer. Tumori. 1994 Dec 31;80(6):464-7.

Lissoni P, Barni S, Tancini G, Ardizzoia A, Ricci G, Aldeghi R, Brivio F, Tisi E, Rovelli F, Rescaldani R, et al. A randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma. Br J Cancer. 1994 Jan;69(1):196-9.

Lissoni P, Barni S, Ardizzoia A, Paolorossi F, Crispino S, Tancini G, Tisi E, Archili C, De Toma D, Pipino G, et al.Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin. Oncology. 1992;49(5):336-9.

Peck, Peggy. Adjuvant chemotherapy associated with survival benefit for early-stage NSCLC. June 7, 2004. Accessed June 9, 2004 from:
http://www.medscape.com/viewarticle/480292

Shepherd, FA, et al. A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1st line or 2nd line chemotherapy. A National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial. Meeting: 2004 ASCO Annual Meeting Abstract No: 7022

**NOTE** To view this page in a more printable format, please CLICK HERE.

IMPORTANT DISCLAIMER

The news and other items in this newsletter are intended for informational purposes only. Nothing in this newsletter is intended to be a substitute for professional medical advice.