Cancer Decisions - Free Newsletter

HERE AT THE MOSS REPORTS

People facing a diagnosis of cancer typically must make a series of crucial treatment decisions in very short order. It can be hard to choose wisely at a time when one is under such intense pressure. The widely praised Moss Reports are an invaluable source of information on currently available conventional and alternative treatments for a wide variety of cancer types. There are now over 240 Moss Reports, each one on a different, specific kind of cancer. For cancer patients and their families a Moss Report offers a truly comprehensive resource, covering the most promising conventional and alternative treatment options as well as a wide variety of other topics of immediate importance to patients currently undergoing treatment and to those who are recovering.

If you would like to order a Moss Report for yourself or someone you love, you can do so securely from our Web site, www.cancerdecisions.com, or by calling 1-800-980-1234 (814-238-3367 from outside the US).

For those who have already purchased a Moss Report on their specific cancer diagnosis, a phone consultation with Ralph Moss can be enormously helpful in narrowing down the options and arriving at a coherent treatment strategy. A recent phone consultation client wrote:

"It was heartening to receive a well-researched unbiased opinion from Ralph Moss. I thank you for being a watchdog over the business of cancer with an objective outlook that is a very useful resource to many. I would recommend your report to anyone with a diagnosis of cancer. Thank you." - M.R.

To schedule an appointment, please call 1-800-980-1234 (814-238-3367 from outside the US) or submit a request via email to Jacquie@cancerdecisions.com.

We look forward to helping you.

CURRENT TOPICS

Also available from our website are our Current Topics reports on cancer-related subjects. Currently available are the following:

On Guard - Gardasil (A discussion of the anti-cervical cancer vaccine Gardasil)
Do Antioxidants and Chemotherapy Conflict?
Mammography, Biopsy and the Diagnosis of Breast Cancer
Herceptin or Deceptin? (An evaluation of the use of Herceptin in breast cancer)
Avastin: Your Money Or Your Life. (A clear-eyed look at the targeted drug Avastin)
The Politics of Hope: Andrew von Eschenbach and the Decline of the National Cancer Institute
The Mexican Cancer Clinics in the Era of Evidence-Based Medicine

AUDIO NEWSLETTER

To hear the audio version of the newsletter, please click or go to:
http://www.cancerdecisions.com/audio/CD111807.mp3

SUBSCRIBE TO OUR PODCAST

To hear the letter podcast on iTunes, please visit:
http://phobos.apple.com/WebObjects/MZStore.woa/wa/viewPodcast?id=215899747

If you do not have iTunes, you may also access our feed at:
http://www.cancerdecisions.com/mossreports.rss

DOES TYKERB REALLY WORK? - PART I

Earlier this year, the US Food and Drug Administration (FDA) approved the drug Tykerb (lapatinib) to treat advanced breast cancer. Tykerb is what is known as a dual tyrosine kinase inhibitor. It inhibits both the erbB-2 receptor (usually abbreviated as HER2 or HER2/neu), and also the epidermal growth factor receptor (EGFR). It is similar to the drug Herceptin (trastuzumab), but differs from it in that the Tykerb molecule is smaller, and, unlike Herceptin, can enter the cell and directly target the gene that produces HER2, while Herceptin is only able to target the cell surface receptor that activates the HER2 gene. There is also some evidence to suggest that Tykerb may be able to cross the "blood-brain barrier" in sufficient quantities to exert a therapeutic effect on cancer that has spread (metastasized) to the brain.

The drug was approved by the FDA for the treatment of advanced or metastatic breast cancer in women whose tumors over-express the HER2 protein. Tykerb is used in combination with the chemotherapeutic drug Xeloda (capecitabine) and is typically given to those women who have been previously treated with other forms of chemotherapy, including an anthracycline drug (most commonly Adriamycin), a taxane (such as Taxol or Taxotere) and Herceptin. Over time, a significant proportion of women taking Herceptin become resistant to it. Tykerb offers these women a further option.

An additional advantage for patients is that both Tykerb and Xeloda are oral medications: they do not have to be given by intravenous infusion in a doctor’s office. Tykerb comes in tablets of 250 mg. A dose is taken once daily for 21 days and in combination with Xeloda on days 1-14 of this 21 day cycle.

According to the manufacturer, GlaxoSmithKline of Research Triangle, NC, clinical trials of Tykerb "demonstrated that the growth of breast cancer was delayed significantly in those patients receiving the combination compared to those taking Xeloda alone." We shall examine these and other claims for this new medication.

There are over 140 scientific articles about Tykerb in the medical database PubMed, but few of these are reports of clinical trials. In fact, most of what is known or stated about the effectiveness of Tykerb comes from a single randomized controlled trial (RCT) performed at the Allegheny Cancer Center in Pittsburgh. In this trial, researchers randomly assigned women with HER2-positive, locally advanced or metastatic breast cancer that had progressed after standard treatment, to receive either Tykerb plus Xeloda or Xeloda alone. The trial was designed to measure "time to progression" - i.e., how long the women’s disease remained stable before it inexorably started to progress again.

The trial found that the median time till progression of the disease was 8.4 months in the Tykerb plus Xeloda group vs. 4.4 months in the Xeloda-alone group. In addition, the tumor shrinkage ("response") rate was higher in the Tykerb plus Xeloda group (23.7 percent) vs.13.9 percent in the Xeloda alone group. There did not appear to be an increase in the most serious toxic effects including symptomatic cardiac events. The authors concluded that Tykerb plus Xeloda was superior to Xeloda alone in these women.

However, the question of whether Tykerb prolongs survival is still open. At the time of approval the FDA said simply that "the survival data are not yet mature." In fact, in the Allegheny Cancer Center study there was no statistically significant survival difference between the two groups. At follow-up, fifty five (28 percent) of the patients in the Tykerb plus Xeloda group had died as compared to 64 of the patients (32 percent) in the group given Xeloda alone.

However, there were reports in the media that a subsequent analysis of the data by GlaxoSmithKline showed that the delay in progression of the disease was actually closer to 7 months (rather than the 8.4 months quoted in the approval data) for the group that received both drugs, as compared to 5 months for those on Xeloda alone (CBS News, March 13, 2007).

Similar Results in Kidney Cancer

Tykerb performed similarly in patients with advanced kidney cancer, according to a report presented at the 2006 meeting of the American Society of Clinical Oncology (ASCO). The drug produced no difference in overall survival nor did it halt disease progression in a group of 416 patients with advanced renal cell carcinoma. The median time to progression was 15.3 weeks for patients given Tykerb vs. 15.4 weeks for those given standard hormone therapy - basically the same. A subset of patients whose tumors expressed EGFR (one of the drug’s specific targets) did experience a modestly prolonged progression-free interval when given Tykerb (15.1 weeks for Tykerb vs. 10.9 weeks for hormone therapy). The median overall survival for this subset was 46 weeks for those given Tykerb versus 37.9 weeks for those given hormone therapy. This amounted to a two-month survival advantage in a selected group of patients.

The most commonly reported adverse effects with Tykerb include diarrhea, nausea, vomiting, rash and hand-foot syndrome (which may include numbness, tingling, redness, swelling and discomfort of hands and feet). According to the FDA, generally reversible decreases in heart function (that can lead to shortness of breath) have also been reported in a small percentage of patients.

In August 2007, however, the FDA amended the Tykerb label to add interstitial lung disease and pneumonitis to the adverse effects of the drug. These lung-related effects were seen in clinical trials with both Tykerb alone and when it was given in combination with other drugs. The FDA recommended discontinuation of the drug in patients who exhibited such symptoms.

TO BE CONCLUDED, WITH REFERENCES, NEXT WEEK

--Ralph W. Moss, Ph.D.

**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.