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Issue 21

Summer 2011

SCCA Leads Head & Neck Cancer Care in the Northwest
Leading the way for Northwest head and neck cancer care, UW Medical Center (UWMC), a parent organization of SCCA, ranked sixth among the top cancer centers in the nation.

Crizotinib — A New Therapy for Lung Cancer Patients
Until very recently, we treated all patients with non-small cell lung cancer (NSCLC) the same way. A patient with advanced disease was treated with one of a few available chemotherapy combinations, usually based on the preference of the treating physician or differences in toxicity profile.

Big News for Prostate Cancer Treatment
There is a new drug in town from Exelixis called XL184 (cabozantinib) which was reported on in three big presentations at this year’s American Society of Clinical Oncology meeting in Chicago.

New Hormonal Therapy in Testing for Late-stage Prostate Cancer
Radiation therapy combined with hormone suppression is a standard approach for treatment of intermediate and high risk prostate cancer, providing better survival outcomes compared to radiation or hormone suppression alone. Data just published in the New England Journal of Medicine shows that androgen deprivation provided a better cure rate for men with intermediate stage and grade prostate cancer, providing radiosensitization to radiation effects.

Transplant Outcomes Continue to Improve
A recent article by SCCA researchers in the New England Journal of Medicine documents improved survival after allogeneic bone marrow transplantation over the past decade.

Pancreas Cancer Drug Inhibits Hedgehog Pathway
This summer, SCCA opened a new clinical trial for metastatic pancreas cancer that is testing IPI-926, a novel, oral, small molecule that inhibits signaling between a pancreas cancer cell and surrounding fibroblasts that support its growth and survival.

U-Link: EMR Access for Referring Providers
Did you know that referring providers in our community can access their patient records in Mindscape? By enrolling in the U-Link program, external providers can immediately view transcripts, labs, medication lists, radiology PACs, and other patient data.

Upcoming CME Events

Comprehensive Oncology Review Course
Saturday through Tuesday, September 17–20, 2011, Seattle

Challenges and Controversies in Breast Cancer — CME
Thursday and Friday, October 20–21, 2011, Seattle


SCCA Leads Head & Neck Cancer Care in the Northwest

Leading the way for Northwest head and neck cancer care, UW Medical Center (UWMC), a parent organization of SCCA, ranked sixth among the top cancer centers in the nation. Their goal is to achieve cure and minimize acute and chronic side effects of therapy.

UWMC was the first medical center to bring robotic surgery to the region and continues to train community physicians in this field. Patients whose tumors can be removed via a minimally invasive approach using the daVinci Robot can expect to return home in only a day or two without experiencing the long-term effects of more invasive techniques. Great advances have been made in reconstructive procedures as well. The newest technique for removing tumors is transoral robotic-assisted surgery (TORS) for tumors of the upper aerodigestive tract (tumors of the back of the tongue and throat).

Using a simultaneous, two-team approach with an oncologic surgeon and a reconstructive surgeon, the length of procedure time is significantly shortened. After surgery, a team of nurses, speech pathologists, and social workers help patients recover and rehabilitate.

If a structure cannot be saved or restored, new ways of helping to improve speech, swallowing, and other functions include restoring vocal ability using a quick implant procedure, the electrolarnyx, a device placed against the neck to help form words, and the tracheosophageal puncture — a surgical procedure that restores the patient’s ability to deliver air into the throat to eventually allow speech.

Head and neck radiotherapy to include proton therapy
SCCA patients are cared for by specialized radiation oncologists with clinical experience specifically in treating head and neck cancers using state-of-the-art technology in a patient-centered approach.

SCCA and ProCure Treatment Centers Inc. broke ground in 2011 for a new proton therapy center in north Seattle that will provide a first-of-its-kind treatment option for cancer patients throughout the Northwest. Scheduled to open in 2013, this facility will be among only a handful of centers in the nation to offer proton therapy, an advanced form of radiation treatment and an important alternative to standard X-ray radiation for many types of cancer and some non-cancerous tumors.

Chemotherapy, in combination with radiotherapy, is now the standard of care for patients with locally advanced disease, either as a primary treatment or after surgical resection. Targeted therapies have improved the efficacy of conventional chemotherapy and in some cases are used alone as a monotherapy.

To refer your patient to SCCA/UWMC for a head and neck cancer, contact us at (206) 288-SCCA or (206) 598-4023.

Crizotinib — A New Therapy for Lung Cancer Patients

By Renato Martins, MD, medical oncologist

Until very recently, we treated all patients with non-small cell lung cancer (NSCLC) the same way. A patient with advanced disease was treated with one of a few available chemotherapy combinations, usually based on the preference of the treating physician or differences in toxicity profile.

In 2004, we recognized that approximately 10 percent of lung cancer patients have in their tumor an activating mutation in the epidermal growth factor receptor (EGFR), which makes them much more sensitive to a therapy using an oral tyrosine kinase inhibitor. Today, one of these agents is the standard of care, as an initial therapy, for patients with tumors harboring these mutations.

Last year we found out that another group of patients, also based on a tumor mutation, have a very significant benefit from an oral agent. Tumors with an EML4-ALK fusion mutation are very sensitive to a new agent called crizotinib, an ALK and MET inhibitor. Like patients with an EGFR mutation, patients with an ALK mutation are more likely to be non or light-smokers and to have adenocarcinoma. They are also younger than other lung cancer patients and tend to have a rare type of adenocarcinoma called signet ring cells.

These mutations are present in approximately 5 percent of patients with NSCLC. In a Phase I trial presented at ASCO in 2010, and now published in the New England Journal of Medicine, patients with this mutation treated with crizotinib had a 57 percent rate of major tumor reduction and median time to progression of 10 months. Based on these data and on preliminary Phase II results, it is likely that crizotinib will be approved in the United States in the near future.

At Seattle Cancer Care Alliance (and parent organizations Fred Hutchinson Cancer Research Center and UW Medicine), we have a number of trials investigating the role of crizotinib. We also perform “in-house” ALK testing by FISH. To see all of our current open trials, go to www.seattlecca.org/clinical-trials.cfm.

Big News for Prostate Cancer Treatment

There is a new drug in town from Exelixis called XL184 (cabozantinib) which was reported on in three big presentations at this year’s American Society of Clinical Oncology meeting in Chicago.

In ongoing Phase II clinical trials, XL184 has unprecedented activity in prostate cancer. It is also active in other cancers. Seattle Cancer Care Alliance has the Phase II XL184 trial open for prostate cancer patients now and will open it for ovarian cancer patients in the near future.

The excitement around this drug comes from its ability to cause regressions in bone scans—bone metastases unlike anything ever seen before. It also seems to be shrinking metastatic tumors in other sites.

“Until recently, no compound has resulted in marked improvements in bone metastases as measured by bone scans in advanced metastatic castrate resistant prostate cancer (mCRPC),” says Dr. Celestia Higano, medical oncologist at SCCA. “However, recent data with cabozantinib have shown marked effects on bone lesions on bone scan paired with alleviation of bone pain as well as shrinkage of measurable tumor lesions. Bone pain alleviation, supported by bone scan response assessment, may provide a possible endpoint for this compound that effectively addresses a clinically relevant, unmet medical need in men with prostate cancer.”

For details and to enroll patients, go to www.seattlecca.org/clinical-trials/prostate-NCT00940225.cfm.

New Hormonal Therapy in Testing for Late-stage Prostate Cancer

By Bruce Montgomery, MD

Radiation therapy combined with hormone suppression is a standard approach for treatment of intermediate and high risk prostate cancer, providing better survival outcomes compared to radiation or hormone suppression alone.[1] Data just published in the New England Journal of Medicine shows that androgen deprivation provided a better cure rate for men with intermediate stage and grade prostate cancer, providing radiosensitization to radiation effects.

Abiraterone (Zytiga) is a new class of hormonal agent designed to more effectively suppress testosterone in the blood and cancer, lowering serum and tissue testosterone levels below those achieved with standard hormonal therapy. The drug works to directly inhibit the process of steroidogenesis by inhibiting the enzyme CYP17 in the adrenal gland and tumor tissue itself. The drug builds on work developed at the University of Washington and Fred Hutchinson Cancer Research Center that shows that prostate cancer can become resistant by producing its own hormones in response to standard hormone deprivation.[2, 3]

Abiraterone improved survival in men with very advanced prostate cancer that was resistant to standard hormonal therapy and chemotherapy, demonstrating that hormone production by the cancer is a relevant mechanism of progression.[4] An ongoing study at SCCA and UWMC is testing the effects of abiraterone with radiation therapy in men who are candidates for radiation with hormonal therapy.

The primary aims of the study are to evaluate the safety of radiation with abiraterone, and to assess the effects of treatment on prostate cancer hormone levels.
Providing more effective hormonal therapy early in the course of treatment may improve both local and systemic control of the disease.

Phase II Trial of Radiation with Androgen Deprivation (RAD): Abiraterone Acetate, Prednisone and LHRH Agonist Prior to and Concurrent with Radiation Therapy. 7048. NCT01023061 www.seattlecca.org/clinical-trials/prostate-7048.cfm

Contact Robyn Haaf, RN at (206) 667-5974, Bruce Montgomery, MD, pager (206) 559-5058, or Ken Russell, MD (206) 288-7100 for more information.

1. Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C et al: Longterm results with immediate androgen
suppression and external irradiation in patients with locally advanced prostate cancer
(an EORTC study): a phase III randomised trial. Lancet 2002, 360(9327):103-106.
2. Mostaghel EA, Page ST, Lin DW, Fazli L, Coleman IM, True LD, Knudsen B, Hess DL, Nelson CC, Matsumoto AM et al: Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res 2007, 67(10):5033-5041.
3. Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, True LD, Nelson PS: Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res 2008, 68(11):4447-4454.
4. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ,
Goodman OB, Jr., Saad F et al: 0ytrewq Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011, 364(21):1995-2005.

Transplant Outcomes Continue to Improve

By Paul Courter, Medical Science Writer

A recent article by SCCA researchers in the New England Journal of Medicine documents improved survival after allogeneic bone marrow transplantation over the past decade. The study compares first allogeneic transplants done at SCCA and Fred Hutchinson Cancer Research Center from 1993 to 1997 with those done from 2003 to 2007.

SCCA researchers found substantial reductions in transplant-related complications (e.g., severe GVHD, infections, organ damage) and death between these time periods. They also noted significant decreases in cancer relapse or progression (−21%) and overall mortality (−41%).

The Seattle data reflect national trends. According to the National Marrow Donor Program (NMDP), one-year transplant-related mortality dropped from 46 percent in 1995-1998 to 26 percent in 2003-2006; one-year survival with unrelated transplantation increased from 42 percent in 1996-2001 to 54 percent in 2002-2006.

What is contributing to the improved outcomes?

Clearly, less toxic conditioning is a major factor. Many patients today, especially those with coexisting conditions, benefit from lower dose myeloablative regi¬mens that allow for adequate anti-tumor activity but with less organ damage.

Reduced-intensity conditioning also greatly expands access to transplant for older patients—nationally, according to the NMDP, the number of allogeneic transplants in patients over age 64 years increased 111 percent from 2006 to 2010.

Another factor is better management of complications. The SCCA group points out, for example, that the 67 percent decrease in grade 3 or 4 GVHD could be due to a 8change in treatment philosophy over the past decade. In particular, minimizing prednisone exposure while managing gastrointestinal GVHD prob¬ably helped to avoid infections as well as renal or pulmonary disease.

Other advances in patient care that may have reduced transplantation risk include: increased use of peripheral-blood donor cells (leading to faster engraftment of neutrophils and earlier protection against fungal and bacterial infections); new antibacterial prophylaxis (such as quinolones instead of cephalosporins); more targeted antifungal and antiviral therapy; and ursodiol prophylaxis to prevent jaundice.

What’s Ahead?

For patients receiving transplants today, refinements in patient care continue to chip away at transplant risks and boost overall survival. In coming years, SCCA transplant experts say that the main drivers of improvement may involve new strategies for reduced-intensity conditioning or, for treatment or prevention of complications, enhanced patient-donor matching, special protocols for unmatched donors, and further adoption of peripheral blood stem cells and cord blood. Many of these ongoing efforts to improve transplantation outcome are being spearheaded right here in Seattle by SCCA clinicians and researchers.

The full article on improved outcomes at SCCA is available from the New England Journal of Medicine website at: www.nejm.org/doi/full/10.1056/NEJMoa1004383.

Pancreas Cancer Drug Inhibits Hedgehog Pathway

This summer, SCCA opened a new clinical trial for metastatic pancreas cancer that is testing IPI-926, a novel, oral, small molecule that inhibits signaling between a pancreas cancer cell and surrounding fibroblasts that support its growth and survival. Inhibition of this Hedgehog signaling pathway represents a fundamentally new approach for addressing a broad range of cancers, including pancreas cancer. (This trial follows directly from research performed by an international team of scientists, including the Fred Hutchinson Cancer Research Center’s Dr. Sunil R. Hingorani.)

The journal Science reported in 2009 that IPI-926 depleted the dense, scar-like stromal tissue surrounding tumors in mice that were genetically engineered to develop pancreas cancer. This led to an increase in blood flow allowing more effective delivery of chemotherapy to the tumor. As a result, IPI-926 enabled a higher response rate to gemcitabine, the current standard of care. Without IPI-926, the stromal tissue prevented the gemcitabine from penetrating tumors.

At this summer’s annual American Society of Clinical Oncology (ASCO) meeting in Chicago, Infinity Pharmaceuticals, Inc. announced results from the Phase Ib portion of this trial which showed that IPI-926 in combination with gemcitabine was well-tolerated, and partial responses were experienced in 31 percent of patients. The historic overall response rate to gemcitabine is less than 10 percent.

“This overall strategy of targeting the supporting tumor microenvironment, or stroma, in combination with therapies against the cancer cell itself holds great promise for improving treatment response in patients with pancreas cancer and represents a new conceptual approach to cancer treatment in general,” said Dr. Hingorani.

Based on these results of the Phase Ib trial, the randomized, double-blind, placebo-controlled Phase II portion of the trial opened in February 2011. This trial compares the combination of IPI-926 with gemcitabine versus placebo with gemcitabine and is actively enrolling metastatic pancreatic cancer patients at SCCA.
For details and to enroll patients, go to www.seattlecca.org/clinical-trials/pancreatic-cancer-NCT01130142.cfm.

U-Link: EMR Access for Referring Providers

Did you know that referring providers in our community can access their patient records in Mindscape? By enrolling in the U-Link program, external providers can immediately view transcripts, labs, medication lists, radiology PACs, and other patient data. This is ideal for them to stay apprised of their patients while they are being cared for at SCCA, UWMC, and Harborview Medical Center. Furthermore, with recent upgrades, U-Link accounts are now available to those providers’ support staff (e.g. RNs, MAs, etc.), and the entire group can share access to the same patients’ records.

For more information about U-Link or to direct community providers to enroll¬ment information, please go to http://uwmedicine.org/u-link or contact the Physician Liaison Program at UWMCPL@uw.edu or (206) 598-5693. Please note that the enrollment process takes about a week, so for immediate patient record ROI needs, providers will still need to contact Patient Data Services at SCCA.

On Creating New Knowledge… and Measuring Results

Dr. Frederick R. Appelbaum is Executive Director of SCCA and also a co-author on the recent New England Journal of Medicine article updating transplant outcomes here in Seattle. He recently commented on the importance of treatment centers tracking outcomes as a guide to improving cancer treatment.

“The only way we can do better is not by hoping, or wishing, or waiting for a miracle. It’s by creating new knowledge. Starting around the year 2000, the federal government required that each transplant center send back data on the outcomes of their transplants. Every year since the year 2000, SCCA and Fred Hutchinson Cancer Research Center has stood at the top in outcomes.”

Upcoming CME Events

 

Comprehensive Oncology Review Course

Saturday through Tuesday, September 17–20, 2011, Seattle
The Comprehensive Oncology Review Course is a four-day intensive review of the data supporting the management of patients with malignant hematologic and solid tumor disorders. Instructed by leading oncology experts chosen for their teaching abilities, participants will receive a comprehensive syllabus and the opportunity to partake in case-based question-and-answer sessions, discus¬sions, and review. Participants will leave with improved proficiency in manage¬ment of patients with malignant disorders. The course will be designed to help prepare you for certifying and re-certifying exams, if applicable.

For more information and to register, go to: www.uwcme.org

Challenges and Controversies in Breast Cancer — CME

Thursday and Friday, October 20–21, 2011, Seattle
This conference is an in-depth, cross-disciplinary review of breast cancer tumor topics in medicine. Leading experts in the fields will present the latest updates and clinical recommendations in breast cancer diagnosis, treatment, and care. The diagnosis and treatment of breast cancer patients is a constantly evolving area of medicine. Clinicians who treat breast cancer patients are increasingly part of a multi-disciplinary team and need to understand new options in the clinical manage¬ment of their patients. Discussion will be based on some of the most late-breaking and controversial areas of breast cancer management.

For more information and to register, go to: www.uwcme.org.

Visit www.seattlecca.org/clinicaltrials and browse through the disease sections to find an appropriate trial for your patients. Make a referral electronically using our easy referral form — see the “refer patient” button on the trial page — or call SCCA at (800) 804-8824. If you have any questions or comments about the web site, contact Tove Thompson at tovethom@seattlecca.org or (206) 288-1233.

 

Newsletter Executive Editor: Norman Hubbard, COO
Editor-in-Chief: Claire Beck Keeler
Editor: Amy Poffenbarger
Medical Editor: James Dean, MD, PhD
 


Adult Bone Marrow Transplant News

The SCCA Adult Bone Marrow Transplant News is a publication presenting the latest information on bone marrow transplant research at SCCA, providing up-to-date information for all health care professionals caring for transplant patients.

Pediatric Bone Marrow Transplant News

Read about important outcomes research at the Fred Hutch that may benefit your patients.

Clinical Trials Monthly

Each issue of Clinical Trials Monthly highlights several of the more than 200 clinical trials that are currently recruiting patients at SCCA.

The Leading Edge Newsletter

Each quarterly Leading Edge newsletter will highlight a new topic to give you the latest news on leading-edge therapies that SCCA physicians are offering.