The Rapid Reporter: May 2007

THE RAPID REPORTER Association of Community Cancer Centers 33rd Annual National Meeting

March 28—31, 2007 Rockville, MD

%u25BA Hospice Care Delayed by Targeted Cancer Drug Discoveries

Oral administration changes perceptions of severity, outcome of illness.

New cancer treatments, which enable patients to take drugs orally instead of by intravenous infusion, are impacting the way terminal cancer is viewed by patients and doctors.

“A better understanding of the recentlyapproved oral agents for cancer is making us lean more toward oral administration and away from intravenous infusion, but we’re changing more than that,” Dr. Alice P. Chen of the National Cancer Institute’s Investigative Drug branch said. “We’re changing patient care trends. Patients are always looking for signs that their disease isn’t terminal, and admission to a hospice confirms it is. Putting patients on oral medications when the response rate may be one percent or less delays acceptance of the terminal nature of the disease and of hospice care.”

Dr. Chen shared her observations during a presentation at the Association of Community Cancer Centers 33rd Annual National Meeting in March.

Hospice providers, she said, are already reporting a ‘backlash’ of sorts from the newly approved oral chemotherapies. “Fewer side

effects and the ability to take medications at home may reinforce a longstanding reluctance to accept that death is approaching,” she said. “Patients may defer enrolling in hospice, or clinicians may wait to refer patients while they try a newer oral medication at the patient’s request.” Patients may suffer needlessly without palliative care and both they and their families have much less time to establish a relationship with the hospice as a result.

%u25BA Counterfeit Drugs: Biopharmaceuticals Not Immune to Crime

Rising costs, availability of oral versions, likely to heighten risk.

Biologic drugs, including cancer treatments, are not immune to the attempts of counterfeiters who try to pass sophisticated-looking fakes offas the real thing, according to one large community cancer services provider.

“Historically, oncolytic agents have been infusible or injectable drugs,” Rolando DeCardenas, vice president of pharmaceutical distribution for US Oncology said at the Association of Community Cancer Centers meeting. “But now that many are available in tablet form, they could potentially be easier to counterfeit.”

Counterfeiters have already infiltrated the biologic cancer therapy market, as illustrated by a spate of adulterated drugs in 2002. Among the list of adulterated pharmaceuticals that year was Procrit (epoetin alfa). Several cases of the Ortho Biotech drug, used to treat chemotherapy-associated anemia, were replaced by vials containing an extremely diluted version which could have caused patients to be underdosed had the fakes not been discovered.

The high price of some of the newer anticancer biologics makes them a target for counterfeiters who, as in the Procrit example, literally water them down and sell them at full price to unsuspecting cancer care centers. “Oncology drugs represented about $40 billion in sales in 2005 and 2006,” Mr. DeCardenas says. “This area is expected to grow to even larger.”

Mr. DeCardenas said oncologists at cancer centers should insist drugs be purchased directly from manufacturers. “It is difficult to tell at the oncologist level if a drug has been adulterated,” he said. “More sophisticated counterfeiters use equipment that makes pills and bottles appear remarkably authentic. These drugs are then sold at steep discounts to secondary wholesalers.” Cancer centers may be tempted to buy from secondary wholesalers rather than manufacturers for lower prices, he said, but these price breaks are rarely passed on to patients.

US Oncology recently implemented an “electronic pedigree” system which tracks the movement of oncology drugs through the supply chain, from plant to patient. Further down the road, Mr. DeCardenas predicts scannable radio frequency identification tags (RFID) will track drug delivery, allowing the recipient to immediately see the drug’s up-to-the-minute travel history.

%u25BA Genetic Counseling Seeks a Niche in Community Cancer Care

More referrals can translate into more lives saved, geneticists say.

As more genetic mutations associated with the potential development of certain cancers are discovered, some genetic counselors say society isn’t keeping up with science.

“A lot of insurers don’t cover genetic counseling by a genetic counselor, so many institutions are responsible for our salary,” said Robert Resta, MS, a certified genetic counselor and supervisor of The Heredity Cancer Clinic of Seattle’s Swedish Medical Center. “This limits the number of genetic counselors available.” There are currently 2,500 certified genetic counselors in the United States, according to Mr. Resta, who specialize in the detection of cancer predisposition and other diseases. Medicare will cover the cost of testing in certain cases, but most state Medicaid programs, which cover people under 65 and the disabled, will not. Each test is about $3,200.

“Doctors have a general tendency to under-refer patients to us,” Mr. Resta says. “This is particularly true, and almost tragic, for those with breast cancer. A small but significant number of women who are predisposed to breast cancer will also be at higher risk for ovarian cancer, which can be prevented with [prophylactic] oophorectomy.”

Beyond mutations of the BRCA1 and BRAC2 genes, which help doctors identify patients who may be at greater risk of developing breast, ovarian or prostate cancer, geneticists can now identify genetic mutations which may indicate a higher hereditary risk of developing stomach, kidney, eye, endocrine, and pancreatic cancers.

Not all patients with select genetic mutations will develop cancer, nor do all patients who develop cancer have a corresponding genetic mutation. However, Mr. Resta says, there has already been at least one case where the family of a young woman who died of ovarian cancer received a substantial out-of-court settlement when it was found she had a BRCA mutation and prophylactic care may have saved or extended her life.

%u25BA Access to Care Concerns Community Cancer Centers

Surgical and pharmacological treatments not the only issues in access to care.

Biotechnology and other scientific advances have extended the lifeexpectancy of many cancer patients over the last decade, but may be making them more inaccessible at the same time.

“There is a lot of excitement about the new treatments coming out as the research the pharmaceutical industry has done in the last decade starts to pay off,” said Christian G. Downs, executive director of the Association of Community Cancer Centers (ACCC). “But is our healthcare system ready for some of these expensive therapies?”

The question was part of the main theme of access to quality cancer care, which underscored the ACCC annual meeting in Baltimore in late March.

“Even people with great insurance who can get any treatment do so at a personal and societal cost,” Mr. Downs said. “Providers struggle with the cost/benefit ratio, too. We need to understand advances in cancer treatment are incremental. A new therapy may come on the market and provide two or three more months of survival at a cost of over $10,000. But in the room we’re [oncologists] are working in, this is a significant step forward.”

Who will ultimately bear the brunt of the cost of novel cancer treatments of the present and future is another access-related concern of the ACCC. “This is a fight that is coming to a head,” Mr. Downs said. “The provider community’s obligation is first and foremost to their patient. That said, they must hold insurers’ accountable to make sure their patients have access to quality treatments. But we must also hold the pharmaceutical industry’s feet to the fire to continue putting out good quality treatments that will continue to move patient care forward.”

Other access-to-care concerns explored by ACCC meeting attendees centered on improving geographic and physical accessibility to cancer care—from how to best serve cancer patients living in rural settings to designing more “patient-friendly” cancer care centers. Where cancer patients were typically sent to one place for radiation treatment and another for chemotherapy, especially at larger medical centers, “we’re starting to see a trend toward combining everything they need under one roof,” Mr. Downs said. “Improving access to quality cancer care can be as simple as that.”

Current Concepts in the Multidisciplinary Management of Colorectal Cancer

Sidney Kimmel Comprehensive Cancer Center at John Hopkins

University

March 28—31, 2007 Baltimore, MD

%u25BA High-Risk Colon Cancer Patients May be Identified at Earlier Stage of Disease

Presence or absence of microsatellite instability can help predict success of chemotherapy in postsurgery, stage II colon cancer patients.

Oncologists may have isolated a genetic marker on color cancer tumors which identifies patients who would benefit from post-surgery chemotherapy and those who would not, a discovery which could potentially reduce recurrence rates among high-risk patients and spare others from additional chemotherapy who would not benefit from it.

Approximately 25% of all stage II colon cancer patients will have a recurrence, even if the cancer is removed while still confined to the colon. The current follow-up standard of treatment for these patients is close postsurgery monitoring for any signs of returning disease.

“Our insights into treatment can now be based on what is known about the tumor,” Dr. Ross Donehower, director of medical oncology at John Hopkins University said. “This is a huge step forward; this is the first time this has been looked at in any respective way.” Dr. Donehower presented the finding to colleagues at a recent colorectal cancer meeting at Baltimore’s John Hopkins University.

The discovery is currently the subject of high-priority phase III clinical trial sponsored by the National Cancer Institute and the Eastern Cooperative Oncology Group (ECOG). Researchers have discovered a link between microsatellite instability (MSI) on the long arm of chromosome 18 in certain stage II colon cancer tumors and progression of disease. “The presence of MSI means a better prognosis and the patient may not have recurrence,” Dr. Donehower said. “But patients with MS stable tumors have a worse prognosis and would probably benefit from chemotherapy after surgery.”

Patients enrolled in the E5202 trial are assigned into two groups. Those considered at low risk for recurrent colon cancer receive the traditional “close monitoring” treatment. Those at high risk of recurrence are randomized into one of two groups: one will receive standard combo chemotherapy of fluorouracil-5FU and oxaliplatin (folfox), the other will receive folfox plus bevacizumab. The trial is still accepting patients.

%u25BA Tumor Expression, Genetic Markers, May Help Tailor Approaches to Colon Cancer

New discoveries may help match the right treatments to the right patients.

While there are more treatment options for colon cancer available now than a decade ago, doctors say their next challenge is to match the right treatment to the right patient.

“We’ve come to a point where we have a number of treatment options but have fallen short on our ability to predict who will respond to which treatment,” Dr. Daniel Laheru, assistant professor of oncology at John Hopkins University said. “Our ability to figure out who will respond to which drug is really critical.”

Doing so would improve survival rates among colon cancer patients in several ways. “Right now, we try one drug or drug combination and keep them on it until the drug stops working or the side effects are too severe,” Dr. Laheru said.

There are several chemotherapy regimens used to treat colon cancer, most are a combination of fluorouracil (5-FU) and leucovorin. Others agents include bevacizumab, capecitabine, cetuximab and panitumumab. These drugs has roughly doubled the average survival rate of advanced stage colon cancer—from 12 months between combos are working in individual patients.

Oncologists hope better understanding the molecular genetics of colon cancer will help create treatments that zero in on tumor cells and interfere with their growth. For example, identification of an overexpression of the enzyme thymidylate synthase (TS), an enzyme key to cell proliferation, can help doctors select which chemotherapy may be most effective for individual patients. “High levels of TS are associated with resistance to 5-FU,” Dr. Laheru said. “If we know someone’s tumor expresses TS, we may consider doing something different.”

Other future strategies may include the combination of 5-FU and radiation therapy for patients with low-risk of recurrent colon cancer, or replacing 5-FU with another drug plus radiation for those with a higher risk of recurrence, based on certain genetic markers. Detecting the duplicative presence of a genotype considered to be associated with a higher risk of colon cancer complications is another strategy on the horizon.

“As encouraging as this is, none of these markers are suggested for consideration for treating colon cancer now,” Dr. Laheru said. “Hopefully this will change in the next year or so.”