Dr. Collins is the Director of the National Human Genome Research Institute (NHGRI).

Dr. Collins also wrote a Perspective for the New England Journal on June 19, 2008 with Dr. Kathy Hudson and M.K. Holohan: Keeping Pace with the Times — The Genetic Non-Discrimination Act of 2008.

Almost 15 years ago, in1995 Dr. Hudson and Dr. Collins wrote an article for Science where they outlined the need for legislation to address insurance discrimination based on genetic tests and family information. In that article — Genetic Discrimination and Health Insurance: An Urgent Need for Reform — they said,

In addition to the real and potentially devastating consequences of being denied health insurance, the fear of discrimination has other undesirable effects. People may be unwilling to participate in research and to share information about their genetic status with their health care providers or family members because of concern about misuse of this information. As genetic research progresses, and preventive and treatment strategies are developed, it will be increasingly important that discrimination and the fear of discrimination not be a roadblock to reaping the benefits.

President George W. Bush signed the Genetic Information Nondiscrimination Act on May 21, 2008.

Patients in the Patient Preference in Adjuvant Therapy (PACT) trial who switched after 6 weeks from weekly 5-FU with leucovorin to oral capecitabine experienced excessive side effects. The trial was designed to determine which approach to treatment patients liked best.

Patients were randomized to two groups:  the first group began treatment with weekly intravenous 5-FU and leucovorin for 6 weeks (start period) and then switched to oral Xeloda for six weeks (switch period).  The second group began with Xeloda during the start period and got 5-FU during the switch period. Finally, patients would choose the treatment they preferred to complete the final 12 weeks of treatment (preference period.)

However, the trial was halted after 40 of a planned 74 patients were enrolled because of the high toxicity in the first group who made the 5-FU to Xeloda switch.  Serious grade 3 or higher side effects in those now getting Xeloda included diarrhea, hand-foot syndrome, and lethargy.  One patient had low white counts with blood infection, and one experienced angina.

During the start period:

• The Xeloda group had moderately higher percentages of severe (grade 3 or higher) side effects than the 5-FU group (28 percent versus 0 percent)
• 44 percent of the Xeloda group required a lower dose or postponed treatments compared to 6 percent of the 5FU group.

Durng the switch period:

• 79 percent of the 5-FU patients who switched to Xeloda had severe grade 3 side effects compared to none of the patients who switched from Xeloda to 5FU.
• Only 2 of 14 5-FU patients who switched to Xeloda were able to tolerate the full dose.

During the preference period:

20 patients reached the end of the twelve of treatment before the study was closed and were able to make a choice of which treatment they preferred.

• 3 patients, who had taken Xeloda in the switch period, had already dropped out of treatment entirely because of severe side effects.
• 5 patients chose to return to Xeloda.  All 5 had taken Xeloda in the start period, switched to 5-FU, and now wanted to return to Xeloda.
• 4 of those 5 patients who returned to Xeloda after the switch period on 5-FU developed severe side effects during the preference period.
• 2 of 12 patients (17 percent) choosing 5-FU developed severe side effects.
• 1 patient, who had been in the original Xeloda arm during the start period and had switched to 5FU, asked to return to Xeloda.  Despite not having side effects from Xeloda during the start period, she developed serious side effects, had a heart attack, and died.

The researchers don’t know the reason that the sequence of 5-FU with leucovorin and Xeloda made such a startling difference in side effects, but they think that leucovorin (folic acid) may be at the bottom of the mystery.  It is possible that leucovorin allows folate to build up in cells and contributes to more serious side effects when Xeloda is begun.

They point out the recent studies that found more side effects from 5-FU and Xeloda in the United States where food is fortified with folic acid.

Although this study looked specifically at treatments that used 5-FU and leucovorin or Xeloda alone, the researchers believe that doctors should also take care with switching combination therapies.

This caution should also be extended to switching patients from combination regimens containing FU/LV to capecitabine-containing equivalents (eg, from infusional FU/LV with oxaliplatin to capecitabine with oxaliplatin).

The team, headed by Dr. Ivo M. Hennig, concluded,

In chemotherapy-naive patients, capecitabine produced more toxicity than FU/LV, but at levels in line with previously reported data. However, treatment with capecitabine after FU/LV caused markedly increased toxicity, indicating a sequence-specific interaction. The mechanism has not been determined, but interaction with intracellularly retained folate after FU/LV therapy is a possibility. Oncologists need to be aware of this risk if considering crossing patients over from FU/LV to capecitabine-based regimens.

SOURCE: Hennig et al., Journal of Clinical Oncology, Volume 26, Number 20, July 10, 2008.

What this means for patients

Patients need to be aware that an immediate switch from intravenous 5-FU given with leucovorin and Xeloda (capecitabine) may be dangerous.  They should discuss such switches carefully with their oncologists.

Because folate in cells may be the reason for increased serious side effects, patients should discuss all sources of supplementary folic acid with their doctors, including that in enriched foods and multivitamins.

The National Institutes of Health Office of Dietary Supplements has more information about folate in food and folic acid supplements.

The pepper was grown in Mexico, but the FDA says that it may not have been contaminated there.  Investigation continues into the source of the contamination.

The FDA and the produce center, Agricola Zaragoza, are working to recall all peppers handled through the center since June 30, 2008.

Consumers should continue to avoid eating raw jalapeno peppers or foods containing them, according to the FDA.

The FDA is also advising high risk populations including infants, the elderly and those with compromised immune systems not to eat raw serrano peppers.  Serrano peppers are similar in shape and color, but smaller than jalapenos.

Tomatoes, according to the FDA, are now safe to eat.

The Centers for Disease Control (CDC) are collaborating with the FDA in investigating the source of the illnesses.

Traditionally canned or powdered nutritional supplement drinks like Ensure® or Boost® have been used to provide support to patients who are having trouble eating during treatment.

As an alternative, soft whip ice cream machines were installed on oncology wards in a hospital in the United Kingdom.  The machines served a premium ice cream which had comparable protein to the nutritional drinks.

Patients were asked to compare the new ice cream to the regular ice cream served by the hospital and to the nutritional drinks.  Results of the patient survey found:

• 74 percent rated the new ice cream tasted good or excellent.
• 78 percent said that it was easy to eat.
• 77 percent preferred the new soft whipped ice cream to regular hospital ice cream.
• 88 percent preferred the new ice cream to nutritional drinks.

The researchers pointed out the importance of having supportive supplements that patients enjoyed and would eat.

The team, led by C.L. Wright, concluded,

The use of ice cream illustrates a positive way forward for the dietetic treatment of malnutrition in cancer patients and further work is planned for the future. The use of branded ice creams provides an acceptable alternative to oral nutritional supplements in cancer patients with chemotherapy and radiotherapy associated mouth problems.

SOURCE: Wright et al.,Journal of Human Nutrition and Dietetics, Volume 21, Number 4, August 2008/

What This Means for Patients

Soft serve ice cream may provide an alternative to nutritional drinks for patients who have difficulty eating.

Discuss it as a possibility with a nutritionist or your doctor.

Cold foods, like ice cream, may cause sudden pain or a feeling that the throat is closing and you can’t get a breath in the days after treatment with Eloxatin® (oxaliplatin).  You should avoid cold foods and drinks during this time.

Patient surveys will be used to understand patient perspectives as they make treatment decisions about chemotherapy after surgery and their experiences throughout chemotherapy and afterwards.  Information will be analyzed and presented to health professionals who work with colon cancer patients.

In addition, patients will provide their opinions about educational materials being developed to help patients make treatment decisions and manage chemotherapy.

In order to be part of the program, patients must:

• Have been diagnosed with stage II or III colon cancer within the past three months.
• Had surgery to remove the cancer.
• Have had a visit to a medical oncologist.
• Be taking chemotherapy or considering taking it. (Patients who have decided not to have chemo are also eligible.)

As part of the program, participants will be asked to finish:

• An initial questionnaire, either online or using pencil and paper
• Three follow-up surveys
• For those with access to the Internet, an evaluation of segments of a new multimedia patient education program.

Participants will receive a stipend of up to $250.

For more information, or to register:

• Call 1-800-535-0109
• Email PatientInfo@ResearchtoPractice.Com

Information will be kept confidential and no names will connected to individual replies.  Names and addresses are necessary only to receive the stipend, and patients who wish to be completely anonymous can donate their stipend to a charity they choose.

More information about Research to Practice.

In a study of over 12,000 Medicare beneficiaries, nearly 40 percent had someone come with them to their medical appointments. More than half were spouses, about a third were adult children. Other companions included roommates, friends, neighbors, and other relatives.

Older and less-educated patients and those who were in poorer health, were more likely to have someone come to the doctor with them. On average, accompanied patients had twice the Medicare medical expenses.

Companions helped with communication during the visit by

• Recording or writing down doctor instructions.
• Providing information about patient illness or needs.
• Asking questions.
• Explaining the doctor’s instructions.

Patients who rated their health the worst also had the strongest satisfaction with their doctor’s care if they were accompanied by someone else.

Jennifer L. Wolff, Ph,D. and Debra L. Roter, Dr.PH., MPH concluded,

Visit companions are commonly present in older adults’ routine medical encounters, actively engaged in care processes, and influential to patients’ satisfaction with physician care. More systematic recognition and integration of visit companions in health care processes may benefit quality of care for a particularly vulnerable patient population.

SOURCE: Wolff et al. Archives of Internal Medicine, Volume 168, Number 13, July 14, 2008.

• John Marshall M.D. is Chief of Hematology/Oncology at the Lombardi Cancer Center at Georgetown University Hospital in Washington, D.C.  He is a specialist in gastrointestinal cancer.
• Neal Merepol M.D. directs the Gastrointestinal Cancer Center at Fox Chase Cancer Center in Philadephia.

They will be joined by Kevin LaMartina, American Cancer Society Patient Navigator at St. Agnes Hospital In Baltimore.

The Diane Rehm Show is broadcast on National Public Radio from WAMU in Washington, D.C.  You can hear the show on local NPR stations or via live streaming from WAMU.

Tumor cells can be found in the blood of cancer patients, but are very rare in healthy people.  Using a technique that identifies and magnetically separates circulating tumor cells, researchers were able to measure the number of circulating cells in a standard amount of blood. They measured circulating tumor cells before treatment began and again several times during treatment.

CT scans were used to measure cancer that wasn’t responding to treatment and was getting worse (progression.) The number of circulating tumor cells (CTCs) was then correlated to progression and then to overall survival.

Three or more cells in 7.5 ml of blood indicated a poor prognosis.

Circulating Tumor Cells to Forecast Prognosis

Before treatment began, about a quarter of patients (26 percent) had three or more CTC’s.  Their progression-free survival and overall survival was significantly poorer than those with fewer CTC’s.  Median progression-free survival was 4.5 months compared to 7.2 months.  Survival  was 9.4 months versus 15.5 months in patients with fewer circulating tumor cells.

Circulating Tumor Cells to Predict Successful Treatment

Blood was drawn and CTCs counted at successive points during treatment.  When the number of cells remained below 3, both progression-free and overall survival were significantly longer.  As the number of cells increased, survival time fell.

Favorable (less than 3) or unfavorable (3 or more) circulating tumor cells could be combined with information from imaging scans to predict median survival time.

• The best survival (18.8 months) occurred when their was no progressive disease found by the first scan after treatment began and CTC was favorable.
• Even in the presence of progressive disease on the initial scan, favorable CTC predicted longer survival (8.3 months).
• When there were unfavorable CTCs and no change on scans, survival was 7.1 months.
• The worst (3.1 months) was when cancer had progressed on the first scan and there were also unfavorable CTC counts.

The research team points out that a variety of chemo regimens were used in determining results in their study which was a drawback.  Survival times varied among regimens, but the trends found by measuring CTCs still were able to provide information about life expectancy for people with metastatic colorectal cancer.

Stephen Cohen M.D. and his colleagues in the United States and the Netherlands concluded,

The number of circulating tumor cells before and during treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic colorectalcancer. CTCs provide prognostic information in addition to that of imaging studies.

SOURCE: Cohen et. al., Journal of Clinical Oncology, Volume 26, Number 19, July 1, 2008.

Watch a video produced by Veridex CellSearch about how circulating tumor cells are analyzed.

The 2005 National Health Survey interviewed 31,000 adults, including 13,500 who were over 50.  It found that 50 percent of people over the age of 50 had been screened for colorectal cancer, but the other half had not.  While this was an improvement over the 43 percent screening rate in 2000, it was far from desirable according to the researchers who analyzed the information.

Jean A. Shapiro, Ph.D., an epidemiologist at the CDC said,

Colorectal cancer is one of the leading cancer killers in the United States, behind only lung cancer. Screening has been shown to significantly reduce mortality from colorectal cancer, but a lot of people are still not getting screened.

Dr. Shapiro pointed out that lack of insurance and a usual source of medical care may be an important part of the problem.  While over 50 percent of people with insurance had been screened, depending on source of insurance, less than a quarter (24.1 percent) of the uninsured were screened.  Almost 52 percent of people who had a regular doctor were screened compared to less than 25 percent of those without a usual source of care.

In addition, Dr. Shapiro said that the expansion of Medicare coverage for screening in 2001 probably also was part of the increase.

She said,

If we can increase the number of people who have health care coverage, we should be able to increase colorectal cancer screening rates.

Other factors affecting screening that the survey revealed included,

• Less education: 60.7 percent of college graduates were screened, compared to 37 percent of those with less than a high school education.
• Lower household income: 58.5 percent of people whose annual household income was $75,000 or more were screened versus 37.4 percent of those who earned less than $20,000.
• Seeing a doctor more often: People who saw a doctor two to five times in the year before the survey were more than two and a half times more likely to be screened than those who had not seen a doctor at all (52.5 percent versus 19.5 percent).

About half of those surveyed who had not been screened reported that they “had never thought about it.” Twenty percent said, “Their doctor didn’t order it.”

SOURCE: American Association for Cancer Research (AACR) News Release, July 14, 2008.

Shapiro et al. Cancer Epidemiology, Biomarkers, and Prevention, Volume 17, Number 7, July 2008.

For information on how C3 is working to increase coverage for colorectal cancer screening and how you can help go to CoverYourButt.Org.

Formerly White House Press Secretary, Snow was diagnosed with colon cancer  in February of 2005.  He had surgery and chemotherapy.  His cancer was in remission until a recurrence in his liver in March, 2007.

His mother also died of colon cancer when Snow was a teenager and she was 38.

When he returned to the White House Press Room late in April of 2007 after several weeks of treatment for the recurrence, he told reporters,

Not everybody will survive cancer,but on the other hand, you have got to realize you’ve got the gift of life, so make the most of it. That is my view, and I’m going to make the most of my time with you.

He wrote about his life with cancer in an essay Cancer’s Unexpected Blessings in Christianity Today in  July 2007.

President and Mrs. Bush expressed their condolences to Snow’s family in a statement from the White House including the following words,

Tony was one of our Nation’s finest writers and commentators. He earned a loyal following with incisive radio and television broadcasts. He was a gifted speechwriter who served in my father’s Administration. And I was thrilled when he agreed to return to the White House to serve as my Press Secretary. It was a joy to watch Tony at the podium each day. He brought wit, grace, and a great love of country to his work. His colleagues will cherish memories of his energetic personality and relentless good humor.

Snow was born in Kentucky on June 1, 1955. He is survived by his wife, Jill Walker, three children, Kendall, Robbie and Kristi Snow, and his father and stepmother, Jim and Dottie Snow.

Snow always wore the yellow LiveStrong cancer survivor wristband, and once told reporters, “I’m a very lucky guy.”