War on cancer.
Subject: Ovarian cancer (Drug therapy)
Antimitotic agents (Dosage and administration)
Antimitotic agents (Research)
Antineoplastic agents (Dosage and administration)
Antineoplastic agents (Research)
Chemotherapy (Methods)
Chemotherapy (Patient outcomes)
Esophageal cancer (Drug therapy)
Soybean products (Health aspects)
Prostate cancer (Diet therapy)
Cancer (Chemotherapy)
Cancer (Methods)
Cancer (Patient outcomes)
Author: Moss, Ralph
Pub Date: 04/01/2012
Publication: Name: Townsend Letter Publisher: The Townsend Letter Group Audience: General; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 The Townsend Letter Group ISSN: 1940-5464
Issue: Date: April, 2012 Source Issue: 345
Topic: Event Code: 310 Science & research
Product: Name: Avastin (Medication) Product Code: 2834140 Anticancer Drugs; 2834146 Chemotherapeutic Drugs NAICS Code: 325412 Pharmaceutical Preparation Manufacturing SIC Code: 2834 Pharmaceutical preparations
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 286257228
Full Text: Avastin and Ovarian Cancer: Any Benefit?

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Avastin (bevacizumab) is, economically speaking, the top cancer drug in the world. Sales in 2010 topped $6.9 billion. One of the reasons for this financial success has been its manufacturer's (Genentech) aggressive campaign to extend Avastin's use to an increasing number of diagnoses. In November 2011, the South San Francisco company was dealt a setback when the Food and Drug Administration (FDA) revoked its approval of Avastin for the treatment of metastatic breast cancer. The agency said that the risks and financial costs outweighed the minimal benefits to women with that particular type of disease. Now, scientists are back with claims that Avastin is effective in ovarian cancer. Two new studies have been put forward as evidence of this effectiveness.

In January 2012, the announcement of Avastin's use in ovarian cancer created quite a bit of media excitement. The lead author of one of these two studies called his results "promising," stating that the drug "clearly has activity in ovarian cancer." Louise Bayne, chief executive of a British patients7 group, Ovacome, told Sky News:

"This heralds a new era of hope for women diagnosed with ovarian cancer, who have previously been faced with a devastating diagnosis plus a lack of innovative treatments. We are delighted that Avastin is now available to women across the country."

The two randomized controlled trials (RCTs) in question were published in December 2011 in the New England journal of Medicine. In both trials, women with advanced ovarian cancer all initially received standard chemotherapy. This was followed by either Avastin or an inert placebo drug. The two trials had different enrollment criteria and administered different doses of Avastin.

The first trial, designated GOG-0218, enrolled around 1900 patients who had newly diagnosed advanced ovarian cancer. Patients would then randomly receive various combinations of chemotherapy, Avastin, and/or placebo. Patients who received chemotherapy followed by placebo had 10.3 months of progression-free survival. Those who received chemotherapy plus Avast in, then followed by placebo, had 11.2 months (i.e., a gain of less than 1 month). But those who received chemotherapy plus a longer period of Avastin experienced 14.1 months of progression-free survival (a gain of 3.8 months).

Progression-free survival equals the amount of time between the start of treatment and the time that disease progression is first seen to occur. It is one measurement of benefit, although most observers believe that it is not as useful as overall survival as an indicator of benefit.

In the second trial, which mainly took place in Europe, patients received chemotherapy followed by half the amount of Avastin that was given in the American trial. In this second study, progression-free survival was 17.3 months for those receiving chemo plus placebo. Those who received chemotherapy followed by Avastin experienced progression-free survival of 19 months, or a gain of 1.7 months. But in an unplanned analysis of a subset of patients, those who received chemotherapy plus placebo had progression-free survival of 10.5 months, while those who received chemotherapy plus this lower dose of Avastin experienced progression-free survival of 15.9 months, a gain of 5.4 months. The overall survival in high-risk patients was 28.8 months vs. 36.6 months in those who received Avastin after chemotherapy, for a gain of 7.8 months. This does seems to indicate that a lower dose of Avastin (7.5 mg/kg) given for seven months may indeed extend the life of high-risk ovarian cancer patients.

This is the source of most of the positive comments that one finds on the Web. There are several factors that lead to caution in reaching that conclusion, however. First of all, these results were not the result of comparing treatment options that were stipulated in the original trial design. They were derived from an unplanned subset analysis. "Such analyses," the NCI commented, "are considered to be less reliable than analyses that are specified before a study's launch."

Second, we have to bear in mind that considerably more patients had serious side effects in the Avastin group. These included severe hypertension (generally manageable with medication) as well as the more serious intestinal perforations. "Deaths that were likely to be related to treatment were also rare, but they were more frequent in women treated with bevacizumab," according to an NCI statement on the trials.

Avastin is also expensive - up to $100,000 per year. This is similar to the net worth of most American families. In other words, this one treatment alone would bankrupt many American families. In the absence of FDA approval, even if patients have health insurance, they typically have to foot that bill. This puts many people in an awful moral and financial dilemma.

Avastin would be a more rational choice were it possible to specify in advance who is likely to respond to it or not. But according to Deborah Armstrong, MD, of the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, there is a lack of clinical or biological markers to indicate which patients are most likely to benefit from the drug or are at increased risk for serious adverse events. Without a marker that identifies those most likely to benefit, she said, "You're just treating everybody, and the subgroup that gets the benefit gets diluted out."

Such a test may however be in the offing. As I pointed out in my latest book, Customized Cancer Treatment, in vitro testing has been overlooked or ignored by the mainstream oncology community. I have written about the work of Larry Weisenthal, MD, Robert Nagourney, MD, and others to develop chemosensitivity assays that can suggest, in advance, who is likely to benefit from anticancer drugs, including Avastin. Interested readers should check out this book, available at Amazon.

Metronomic Chemo Offers Hope in Esophageal Cancer

Metronomic chemotherapy is now being used in the US with some preliminary success in difficult-to-treat cancers. Nick Chen, MD, PhD, an oncologist who serves as medical director of the Seattle Cancer Treatment and Wellness Center (Renton, WA), uses smaller-than-usual doses of chemotherapy administered more frequently to get a better response with fewer adverse effects.

Dr. Chen went to medical school in Shanghai, China, and studied immunology in Europe. He then completed his training at the University of Nebraska and at the H. Lee Moffitt Cancer Center in Tampa, Florida. I recently visited Dr. Chen at the Seattle center. He works closely with naturopathic physicians, including Mark Guinac, ND, and Paul Reilly, ND, at this outpatient branch of the Cancer Treatment Centers of America (CTCA).

"We don't want to use high-dose chemotherapy that treats the cancer but knocks the patient out as well, so that they have less of a chance to recover," he said. This approach is "very complementary to the supportive treatment we give to all our patients." Nowadays, the representatives of many medical centers talk about integrative oncology. But true integration and individualization is still rare in the US. I was impressed with the level of integration that I found in the Pacific Northwest, an area that has rich traditions of both naturopathic and conventional medicine.

"My own life is extended and enriched by this journey," Nick Chen said.

The basic idea is not just to treat the cancer, but to treat the patient.

One case has generated considerable attention. R.N. had stage IV cancer of the gastroesophageal (GE) junction, a kind of esophageal cancer that is frequently linked to chronic gastric reflux. He was given three or four months to live by the first oncologist that he consulted. It was his wife who then found the Seattle center online. R.N.'s treatment consisted of weekly eight-hour chemotherapy sessions. When combined with naturopathic treatments, this more-frequent regimen was very successful. At this writing, R.N. is in complete remission of his disease.

Soy May Help in Prostate Cancer

A small clinical study from Pennsylvania State University, Hershey, suggests that soy intake may slow an increase in prostate specific antigen (PSA) in men with the type of prostate cancer (PC) that fails to respond to surgery or radiation.

It is well known that a rise in serum PSA following definitive radiation or surgery for prostate cancer indicates a failure of the primary treatment. One option for such men is then androgen deprivation therapy. Such treatment reduces the amount of testosterone, a hormone that can increase the growth rate of PC. But androgen deprivation has significant side effects and is hardly effective for all men who use it.

Monika Joshi, MD, an oncology fellow at the Penn State Hershey Cancer Institute, enrolled 10 men who had treatment-resistant PC that had not yet metastasized. She and her colleagues assigned these men to receive three servings of soy per day for two years. During this time, their PSA levels were periodically monitored.

After two years, half of the men showed a response to soy. This was measured as a temporary or permanent decline in PSA levels or establishment of a stable PSA level. One of three patients whose PSA was rising even while on androgen-deprivation therapy had a positive response to soy treatment.

"Our findings are fairly congruent with what has been described in the literature on the use of this modality in prostate cancer/' Joshi said. "We also show that soy can provide benefit in castration-resistant prostate cancer. Our clinical experience suggests that soy supplementation using commercially available soy products can have durable beneficial effects on PSA levels and PSA kinetics in some men with prostate cancer."

"The results from Pennsylvania State University appear consistent with a considerable amount of published research showing that soy may help to prevent prostate cancer and may be useful in its treatment," said oncologist Omer Kucuk, MD, chief of genitourinary medical oncology at Emory University's Winship Cancer Institute. "For men unresponsive to surgery and radiation for prostate cancer, it is critically important to find androgen deprivation therapy alternatives, such as soy as a dietary intervention. While this study is small, it's important because it takes place in real-life conditions in a clinical setting."

The Penn State research follows a number of other studies showing that soy is protective against aggressive PC. For example, in an Australian study from 2004, Fabien S. Dalais and colleagues at Monash University showed that the addition of heat-treated soy grits (when incorporated in bread) had a major positive effect on the PSA of men awaiting treatment for PC. Compared with plain wheat bread (which is low in anticancer phytoestrogens), total PSA went down 12.7% compared with a rise in PSA of 40% in the wheat-treated group. There also was an improvement in the free/total PSA ratio of 27.4% compared with a harmful decline of 15.6% in the wheat-alone group.

Soy is very attractive as a potential cancer treatment. It is extremely versatile, relatively inexpensive, and widely available. It can also be part of delicious and healthful meals. According to Andrew Weil, MD, one serving equals 1/2 a cup of tofu or tempeh, 1 cup of soymilk, 1/2 cup of cooked edamame beans, or 1 ounce of soy nuts. He advises patients to choose whole soy foods over fractionated foods such as isolated soy protein powders or imitation meats made with soy isolates. Three servings would equal 1(1/2) cups of tofu, or slightly less than what is contained a typical 14 oz. package. A "brick" of tofu generally costs between $3 and $4. Three ounces of soy nuts runs about a dollar and a half. This is a small charge for a potentially big payoff. By comparison, it is infinitesimally less than the $93,000 that Dendreon Corporation is currently charging for three injections of its anti-prostate-cancer drug, Provenge.

References

Perren TJ, Swart AM, Pfisterer J, et al.; ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-2496.

Burger RA, Brady MF, Bookman MA, et al; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-2483.

Kaplan K. Is Avastin a cost-effective treatment for ovarian cancer patients? Los Angeles Times. Dec. 29, 2011.

Moore T. Ovarian cancer drug "heralds new era of hope." Sky News. Jan. 17, 2012. Access at: http://news.sky.com/home/uk-news/article/16150487.

NCI Cancer Bulletin. Jan. 10, 2012. Access at: http://www.cancer.gov/ncicancerbulletin/011012/page2.

Dalais FS, Meliala A, Wattanapenpaiboon N, et al. Effects of a diet rich in phytoestrogens on prostate-specific antigen and sex hormones in men diagnosed with prostate cancer. Urology. 2004 Sep;64(3):510-515.

by Ralph Moss, PhD www.cancerdecisions.com

Ralph W. Moss, PhD, is the author of 12 books on cancer-related topics. The former science writer at Memorial Sloan-Kettering Cancer Center, for 35 years Moss has investigated the validity of many cancer treatments. He currently directs the Moss Reports, a library of reports for patients on over 200 different cancer diagnoses.
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