ACKC e-Newsletter Volume 1 Number 1

Statement from the Editor

Welcome to the first edition of ACKC’s E-newsletter. We intend to present news concerning the latest therapies and other topics of interest to the kidney cancer survivor and caregiver community. If you have any comments about items in the newsletter or would like to see certain issues covered in the future, please send an email to newsletter@ackc.org. In some cases, the newsletter may present a brief summary, for example, a review article on the results of a clinical trial for a new therapy, and provide you with a link to the full article on our website.

Pfizer is Announcing a New Phase 3 Trial for Axitinib (AG-013736)

ACKC has been following the progress of axitinib in kidney cancer since the favorable results of an early Phase 2 trial were announced at the ASCO conference in the summer of 2005. At that time, Pfizer indicated that despite the favorable results, they were not prepared to continue testing the drug for kidney cancer (this was about the same time that Pfizer was developing Sutent for metastatic kidney cancer). We initiated a campaign (having survivors and caregivers write letters to Pfizer executives and meeting regularly with Pfizer representatives) to get Pfizer to reverse its position and develop the drug. It has been a three-year struggle to get to this point, but through the determined efforts of oncologists, advocates, and even some Pfizer developers, now we are seeing the results. Pfizer will soon announce the opening of a large scale, Phase 3 randomized trial in the U.S. and 20 other countries testing axitinib versus sorafenib (Nexavar) in patients who have previously failed a therapy, either cytokine (Interleukin-2 or Interferon) or a targeted therapy including Sutent. Pfizer expects to start the trial this summer and hopes to get the first site, which we have heard will be Memorial Sloan-Kettering, approved in June.

Axitinib has the potential of being the best of the targeted therapies. The Phase 3 trial seeks to demonstrate axitinib’s effectiveness as measured against a standard targeted therapy in current use, Nexavar. If it is shown to be successful, Pfizer will have ample data to present to the FDA to seek official approval for the drug as another therapy against renal cell carcinoma. See ClinicalTrials.gov at http://tinyurl.com/63p93a for trial details.

For the latest trial results on axitinib, Olivier Rixe of Pitie-Salpetriere Hospital in Paris, the Principal Investigator, reported in an article in Lancet (http://tinyurl.com/4aclk9), that in a Phase 2 trial for cytokine refractory patients, axitinib had an objective response rate of 44% including two complete responders (although half the responders progressed during the study). Another 42% showed stable disease for longer than 8 weeks. Median time to progression was 15.7 months. The most common grade 3 or 4 adverse events were diarrhea, hypertension, or fatigue, which were considered manageable. The results of this trial compare favorably to those of other targeted therapies including Sutent. For a complete review of Rixe article, go to our website at http://ackc.org/pfizer.

NIH Public Access Policy

As of April 7, 2008, researchers who receive funding from the National Institutes of Health are required to make the published results of their work freely available to the public via the National Library of Medicine’s digital archive PubMed Central (http://www.pubmedcentral.nih.gov/) within one year of publication in scientific and medical journals. This new law will affect 80,000 papers per year but leaves out those studies not funded by the NIH. According to Harold Varmus, a previous Director of the NIH and current President of Memorial Sloan-Kettering Cancer Center, the one-year wait time can safely be shortened to six months without threatening the journals’ profits. ACKC is joining the Alliance for Taxpayer Access, which supports open access to all peer-reviewed scientific articles on research funded by the U.S. Government.

American Association for Cancer Research (AACR) Conference

ACKC attended the AACR Conference, which took place April 12-16 in San Diego. 29,000 researchers, advocates, and other interested members of the public attended. The following are summaries of some of the presentations.

Efficacy of Sunitinib (Sutent) Administered on an Intermittent or Daily Dosing

Brett Houk, a Pfizer pharmacologist, presented the results of a retrospective study of the efficacy of sunitinib treatment in RCC and GIST patients for two dosing schedules, the standard 6-week cycle of 50 mg/day, 4 weeks on, 2 weeks off (4/2) versus continuous daily dosing (CDD) of 37.5 mg/day.

He reviewed the following trial data: for GIST, three Phase I-III Trials as follows: (a) 50 mg/day schedule 4/2 67 patients, (b) 50 mg/day schedule 4/2 211 patients (59 placebo), (c) 37.5 mg/day CDD 15 patients; for RCC, three Phase II Trials as follows: (a) 50 mg/day schedule 4/2 54 patients, (b) 50 mg/day schedule 4/2 92 patients, (c) 37.5 mg/day schedule CDD 51 patients; and one Phase III Trial 50 mg/day schedule 4/2 42 patients.

Through his own and others analyses, Houk showed that for both RCC and GIST, sunitinib shows greater efficacy in patients with higher exposure in terms of time to progression, overall survival, and changes in tumor size. After reviewing the above trial data, Houk concluded that, for RCC and GIST, sunitnib is equally effective at the 37.5 mg/day continuous daily dosage as the 50 mg/day four weeks on two weeks off schedule. Unfortunately, he did not present data for the difference in adverse events between the two protocols.

AV-951 Phase 1 Trial Results

Results were announced for this highly potent drug in a 41-patient Phase 1 trial in which 9 patients had RCC. Overall, 33% of the patients showed a response. For the RCC patients, two showed partial response, six had stable disease, and one had disease progression. The maximum tolerated dose was established at 1.5 mg/day. Hypertension was the prominent side effect. A Phase 1b trial using AV-951 and temsirolimus (Torisel) has since commenced. See complete review of the trial at our website http://www.ackc.org/node/175.

B7-H1

The presence of the protein B7-H1 in clear cell tumors has been shown to lead to poor prognosis of cancer patients. In this study, Mayo Clinic researchers hypothesize that B7-H1 acts as an immune system suppressor by killing off a certain type of immune cells that would normally activate T-cells that fight the tumor. For a full report of this study got to ACKC’s website at http://www.ackc.org/node/175.

AACR Sessions on Smoking Cessation, Exercise, and Diet

Memorial Sloan-Kettering Cancer Hospital’s Dr. Jimmie C. Holland hosted a series of speakers in a seminar on the topics of health behavior and lifestyle in cancer survivors. The United States is currently home to over 10 million cancer survivors whose health is generally worse than that of the general population. For individuals who have survived cancer, the precautionary measures taken in lifestyle choices – exercise, diet and smoking cessation – are of even greater importance, and have frequently proven to be successful in the avoidance of further disease.

The speakers Holland hosted – Jamie Ostroff, PhD, from Memorial Sloan-Kettering Cancer Hospital; Kerry Courneya, PhD, from the University of Alberta, Canada; and Wendy Demark-Wahnefried, PhD, from the MD Anderson Comprehensive Cancer Center – addressed the topics of smoking, exercise and diet among cancer survivors, respectively. Each offered compelling research supporting the positive effects of quitting smoking, exercising and eating healthily. See ACKC’s website for a full report on their presentations at http://www.ackc.org/node/175.

American Society for Clinical Oncology (ASCO) Conference

The ASCO Conference, the leading oncology conference in the world, took place in Chicago, May 30-June 3. Over 30,000 oncologists and others attended to hear the latest developments in cancer therapeutics. 108 abstracts were presented at ASCO in the Kidney Cancer category. ACKC attended and we will post reviews of selected presentations on our website as we have done in the past three years. They will be found at www.ackc.org under Kidney Cancer Info->ASCO Reports->Report from ASCO 2008 commencing the week of June 23rd. Reports will be added on a flow basis. In our next newsletter, we’ll summarize some of the important renal cell presentations.

ACKC T-Shirts

One of our members, Patsy Barr, is selling ACKC T-Shirts to benefit our organization. To order them, go to her website http://www.zazzle.com/patsybarr.

[T-shirts]