20091029-1

The New York Times, October 28, 2009, by Gina Kolata  –  Call it the arrow of cancer. Like the arrow of time, it was supposed to point in one direction. Cancers grew and worsened. But as a paper in The Journal of the American Medical Association noted last week, data from more than two decades of screening for breast and prostate cancer call that view into question. Besides finding tumors that would be lethal if left untreated, screening appears to be finding many small tumors that would not be a problem if they were left alone, undiscovered by screening. They were destined to stop growing on their own or shrink, or even, at least in the case of some breast cancers, disappear.

“The old view is that cancer is a linear process,” said Dr. Barnett Kramer, associate director for disease prevention at the National Institutes of Health. “A cell acquired a mutation, and little by little it acquired more and more mutations. Mutations are not supposed to revert spontaneously.”

So, Dr. Kramer said, the image was “an arrow that moved in one direction.” But now, he added, it is becoming increasingly clear that cancers require more than mutations to progress. They need the cooperation of surrounding cells and even, he said, “the whole organism, the person,” whose immune system or hormone levels, for example, can squelch or fuel a tumor.

Cancer, Dr. Kramer said, is a dynamic process.

It was a view that was hard for some cancer doctors and researchers to accept. But some of the skeptics have changed their minds and decided that, contrary as it seems to everything they had thought, cancers can disappear on their own.

“At the end of the day, I’m not sure how certain I am about this, but I do believe it,” said Dr. Robert M. Kaplan, the chairman of the department of health services at the School of Public Health at the University of California, Los Angeles, adding, “The weight of the evidence suggests that there is reason to believe.”

Disappearing tumors are well known in testicular cancer. Dr. Jonathan Epstein at Johns Hopkins says it does not happen often, but it happens.

A young man may have a lump in his testicle, but when doctors remove the organ all they find is a big scar. The tumor that was there is gone. Or, they see a large scar and a tiny tumor because more than 95 percent of the tumor had disappeared on its own by the time the testicle was removed.

Or a young man will show up with a big tumor near his kidney. Doctors realize that it started somewhere else, so they look for its origin. Then they discover a scar in the man’s testicle, the only remnant of the original cancer because no tumor is left.

Testicular cancer is unusual; most others do not disappear. But there is growing evidence that cancers can go backward or stop, and researchers are being forced to reassess their notions of what cancer is and how it develops.

Of course, cancers do not routinely go away, and no one is suggesting that patients avoid treatment because of such occasional occurrences.

“Biologically, it is a rare phenomenon to have an advanced cancer go into remission,” said Dr. Martin Gleave, a professor of urology at the University of British Columbia.

But knowing more about how tumors develop and sometimes reverse course might help doctors decide which tumors can be left alone and which need to be treated, something that is now not known in most cases.

Cancer cells and precancerous cells are so common that nearly everyone by middle age or old age is riddled with them, said Thea Tlsty, a professor of pathology at the University of California, San Francisco. That was discovered in autopsy studies of people who died of other causes, with no idea that they had cancer cells or precancerous cells. They did not have large tumors or symptoms of cancer. “The really interesting question,” Dr. Tlsty said, “is not so much why do we get cancer as why don’t we get cancer?”

The earlier a cell is in its path toward an aggressive cancer, researchers say, the more likely it is to reverse course. So, for example, cells that are early precursors of cervical cancer are likely to revert. One study found that 60 percent of precancerous cervical cells, found with Pap tests, revert to normal within a year; 90 percent revert within three years.

And the dynamic process of cancer development appears to be the reason that screening for breast cancer or prostate cancer finds huge numbers of early cancers without a corresponding decline in late stage cancers.

If every one of those early cancers were destined to turn into an advanced cancer, then the total number of cancers should be the same after screening is introduced, but the increase in early cancers should be balanced by a decrease in advanced cancers.

That has not happened with screening for breast and prostate cancer. So the hypothesis is that many early cancers go nowhere. And, with breast cancer, there is indirect evidence that some actually disappear.

It is harder to document disappearing prostate cancers; researchers say they doubt it happens. Instead, they say, it seems as if many cancers start to grow then stop or grow very slowly, as has been shown in studies like one now being done at Johns Hopkins. When men have small tumors with cells that do not look terribly deranged, doctors at Johns Hopkins offer them an option of “active surveillance.” They can forgo having their prostates removed or destroyed and be followed with biopsies. If their cancer progresses, they can then have their prostates removed.

Almost no one agrees to such a plan. “Most men want it out,” Dr. Epstein said. But, still, the researchers have found about 450 men in the past four or five years who chose active surveillance. By contrast, 1,000 a year have their prostates removed at Johns Hopkins. From following those men who chose not to be treated, the investigators discovered that only about 20 percent to 30 percent of those small tumors progressed. And many that did progress still did not look particularly dangerous, although once the cancers started to grow the men had their prostates removed.

In Canada, researchers are doing a similar study with small kidney cancers, among the few cancers that are reported to regress occasionally, even when far advanced.

That was documented in a study, led by Dr. Gleave that compared an experimental treatment with a placebo in people with kidney cancer that had spread throughout their bodies.

As many as 6 percent who received a placebo had tumors that shrank or remained stable. The same thing happened in those who received the therapy, leading the researchers to conclude that the treatment did not improve outcomes.

The big unknown is the natural history of many small kidney tumors, many of which are early kidney cancers. How often do small tumors progress? Do they ever disappear? Do they all need surgical excision? At what stage do most kidney cancers reach a point of no return?

These days, Dr. Gleave said, more patients are having ultrasound or CT scans for other reasons and learning that there is a small lump on one of their kidneys. In the United States, the accepted practice is to take those tumors out. But, he asks, “Is that always necessary?”

His university is participating in a countrywide study of people with small kidney tumors, asking what happens when those tumors are routinely examined, with scans, to see if they grow. About 80 percent do not change or actually regress over the next three years.

With early detection, he said, “our net has become so fine that we are pulling in small fish as well as big fish.” Now, he said, “we have to identify which small fish we can let go.”

The New York Times, October 2009, by Gina Kolata  –  The American Cancer Society, which has long been a staunch defender of most cancer screening, is now saying that the benefits of detecting many cancers, especially breast and prostate, have been overstated.

It is quietly working on a message, to put on its Web site early next year, to emphasize that screening for breast and prostate cancer and certain other cancers can come with a real risk of overtreating many small cancers while missing cancers that are deadly.

“We don’t want people to panic,” said Dr. Otis Brawley, chief medical officer of the cancer society. “But I’m admitting that American medicine has overpromised when it comes to screening. The advantages to screening have been exaggerated.”

Prostate cancer screening has long been problematic. The cancer society, which with more than two million volunteers is one of the nation’s largest voluntary health agencies, does not advocate testing for all men. And many researchers point out that the PSA prostate cancer screening test has not been shown to prevent prostate cancer deaths.

There has been much less public debate about mammograms. Studies from the 1960s to the 1980s found that they reduced the death rate from breast cancer by up to 20 percent.

The cancer society’s decision to reconsider its message about the risks as well as potential benefits of screening was spurred in part by an analysis published Wednesday in The Journal of the American Medical Association, Dr. Brawley said.

In it, researchers report a 40 percent increase in breast cancer diagnoses and a near doubling of early stage cancers, but just a 10 percent decline in cancers that have spread beyond the breast to the lymph nodes or elsewhere in the body. With prostate cancer, the situation is similar, the researchers report.

If breast and prostate cancer screening really fulfilled their promise, the researchers note, cancers that once were found late, when they were often incurable, would now be found early, when they could be cured. A large increase in early cancers would be balanced by a commensurate decline in late-stage cancers. That is what happened with screening for colon and cervical cancers. But not with breast and prostate cancer.

Still, the researchers and others say, they do not think all screening will – or should – go away. Instead, they say that when people make a decision about being screened, they should understand what is known about the risks and benefits.

For now, those risks are not emphasized in the cancer society’s mammogram message which states that a mammogram is “one of the best things a woman can do to protect her health.”

Dr. Brawley says mammograms can prevent some cancer deaths. However, he says, “If a woman says, ‘I don’t want it,’ I would not think badly of her but I would like her to get it.”

But some, like Colin Begg, a biostatistician at Memorial Sloan-Kettering Cancer Center in New York, worry that the increased discussion of screening’s risks is going to confuse the public and make people turn away from screening, mammography in particular.

“I am concerned that the complex view of a changing landscape will be distilled by the public into yet another ‘screening does not work’ headline,” Dr. Begg said. “The fact that population screening is no panacea does not mean that it is useless,” he added.

The new analysis – by Dr. Laura Esserman, a professor of surgery and radiology at the University of California, San Francisco, and director of the Carol Frank Buck Breast Care Center there, and Dr. Ian Thompson, professor and chairman of the department of urology at The University of Texas Health Science Center, San Antonio – finds that prostate cancer screening and breast cancer screening are not so different.

Both have a problem that runs counter to everything people have been told about cancer: They are finding cancers that do not need to be found because they would never spread and kill or even be noticed if left alone. That has led to a huge increase in cancer diagnoses because, without screening, those innocuous cancers would go undetected.

At the same time, both screening tests are not making much of a dent in the number of cancers that are deadly. That may be because many lethal breast cancers grow so fast they spring up between mammograms. And the deadly prostate ones have already spread at the time of cancer screening. The dilemma for breast and prostate screening is that it is not usually clear which tumors need aggressive treatment and which can be left alone. And one reason that is not clear, some say, is that studying it has not been much of a priority.

“The issue here is, as we look at cancer medicine over the last 35 or 40 years, we have always worked to treat cancer or to find cancer early,” Dr. Brawley said. “And we never sat back and actually thought, ‘Are we treating the cancers that need to be treated?’ ”

The very idea that some cancers are not dangerous and some might actually go away on their own can be hard to swallow, researchers say.

“It is so counterintuitive that it raises debate every time it comes up and every time it has been observed,” said Dr. Barnett Kramer, associate director for disease prevention at the National Institutes of Health.

It was first raised as a theoretical possibility in the 1970s, Dr. Kramer said. Then it was documented in a rare pediatric cancer, but was dismissed as something peculiar to that cancer. Then it was discovered in common cancers as well, but it is still not always accepted or appreciated, he said.

But finding those insignificant cancers is the reason the breast and prostate cancer rates soared when screening was introduced, Dr. Kramer said. And those cancers, he said, are the reason screening has the problem called overdiagnosis – labeling innocuous tumors cancer and treating them as though they could be lethal when in fact they are not dangerous.

“Overdiagnosis is pure, unadulterated harm,” he said.

Dr. Peter Albertsen, chief and program director of the urology division at the University of Connecticut Health Center, said that had not been an easy message to get across. “Politically, it’s almost unacceptable,” Dr. Albertsen said. “If you question overdiagnosis in breast cancer, you are against women. If you question overdiagnosis in prostate cancer, you are against men.”

Dr. Esserman hopes that as research continues on how to advance beyond screening, distinguishing innocuous tumors from dangerous ones, people will be more realistic about what screening can do.

“Someone may say, ‘I don’t want to be screened’ ” she said. “Another person may say, ‘Of course I want to be screened.’ Just like everything in medicine, there is no free lunch. For every intervention, there are complications and problems.”

By THE NEW YORK TIMES

Most who enroll in clinical trials say they want to help themselves and others. But how can patients decide that a trial is worth their while?

Dr. Steven Goodman, professor of oncology in the division of biostatistics of the Johns Hopkins Kimmel Cancer Center, suggests asking doctors some questions:

¶Are there any other trials looking at this or other treatments for people like me here or elsewhere? If so, why should I enroll in this one?

¶Do you think the question being asked in this trial is important? Why or why not?

¶Has this question ever been studied before, and if so, what did those studies show?

¶Realistically, what do you think is the biggest difference likely to be seen in this trial, and how likely is that?

¶What do you think are the biggest downsides?

¶Who is paying for the trial?

¶Do you anticipate having any problem (or are you having problems) recruiting the necessary number of patients for this trial?

¶Would you recommend this trial to a relative?

20091029-2

LOOKING INSIDE This X-ray shows a mass in the upper lobe of the right lung. A clinical trial’s results are spurring a move toward maintenance therapy for lung cancer. 

 

By ANDREW POLLACK, For The New York Times

The newest prognosis for cancer may be longer chemotherapy.

Doctors and pharmaceutical companies are moving toward treating cancer patients with drugs continuously, even when they may not urgently need them. That would be a departure from the common practice of stopping treatment when the cancer is under control and resuming it only if the cancer worsens.

The strategy is called maintenance therapy – akin to periodic tune-ups aimed at preventing a car from breaking down. Doctors say it could prolong the time tumors are under control, helping to turn cancer into a chronic disease that is kept in check even if it is not cured.

While maintenance therapy is not entirely new, its use is growing, in part because some of the newer cancer drugs are more tolerable than the toxic ones of old and can be taken for longer periods.

At the recent annual meeting of the American Society of Clinical Oncology, for instance, doctors filled a huge auditorium for a debate on whether it is time to adopt maintenance therapy for lung cancer, the nation’s leading cause of cancer death. Other cancers for which maintenance therapy is being used or tried include ovarian cancer, multiple myeloma and non-Hodgkin’s lymphoma.

But some experts say that in many cases, the longer-term use of drugs has not been proved to prolong life.

Instead, it may just subject cancer patients to more side effects and tens of thousands of dollars in extra costs. There is also concern that tumors might become resistant to a drug used for a long time.

“Generally more is better, in both dose and potentially duration,” said Dr. Susan L. Kelley, chief medical officer of the Multiple Myeloma Research Foundation, which sponsors research on treatments for that disease. However, she said, “there are numerous kinds of cost to the patient, to the health system, to give these drugs over the longer term.”

Dr. Lawrence H. Einhorn, a professor at Indiana University, said much of the push for maintenance therapy was coming from pharmaceutical companies, which want their drugs “to be used as early as possible and as long as possible.”

And executives of these companies acknowledge that the therapy would mean bigger sales. “This is clearly a game-changing opportunity,” Brian P. Gill, vice president for corporate communications at Celgene, which is testing its drug Revlimid for maintenance treatment of multiple myeloma, told investors at a conference in March.

But the executives, and many doctors, say there is a good rationale for maintenance therapy.

Although treatment varies with the type of cancer, many patients now receive several initial cycles of chemotherapy. Then, if the cancer goes into remission, or even if the tumor simply stops growing, the therapy is stopped. It is resumed, usually with different drugs, only when the cancer starts worsening again.

That strategy evolved in part because the older chemotherapy drugs were so toxic that patients often needed to take a holiday from treatment.

“But if you think about it practically, you don’t really want to give the tumor a holiday,” said Colin Goddard, the chief executive of OSI Pharmaceuticals, which is trying to position its lung cancer drug Tarceva for use in maintenance therapy.

Some cancer patients welcome, or even demand, maintenance therapy, wanting to keep up the fight against their disease.

“I was one of those people who was frightened to stop chemo,” said Barbara Platzer, 71, of St. Louis, who has ovarian cancer.

So when her initial six cycles of chemotherapy ended with her cancer in remission, she enrolled in a clinical trial that provided her with 12 monthly maintenance treatments of an experimental drug called Xyotax. The results of the trial are not yet known, but Ms. Platzer’s cancer has remained in remission.

But Caryl Castleberry of Glen Ellen, Calif., who also has ovarian cancer, turned down maintenance therapy.

“I could hardly wait to be free from treatment, so the extra year they suggested was just not acceptable,” said Ms. Castleberry, 61, whose cancer has nonetheless remained in remission for six years.

Dr. Robert L. Coleman, an expert on ovarian cancer at the M. D. Anderson Cancer Center in Houston, said that because relapses tend to be fatal, there has been an urgent effort to prevent or delay them. But over the years, eight maintenance therapies failed in clinical trials.

Finally, a study published in 2003 showed that 12 monthly maintenance treatments of paclitaxel, a generic drug whose brand name is Taxol, delayed tumor progression by about seven months as compared with 3 monthly treatments with the same drug. But the difference in survival was not statistically significant, Dr. Coleman said, so there is still some debate about the merits of maintenance therapy for ovarian cancer.

For lung cancer, the move to maintenance therapy is being spurred by the results of a clinical trial of the drug Alimta that were presented at the oncology meeting in Orlando, Fla., in late May. Based on that trial, both the Food and Drug Administration and European regulators approved the use of Alimta for maintenance therapy earlier this month.

The trial, sponsored by Eli Lilly, which makes Alimta, involved 663 patients with advanced cancer whose tumors had shrunk or remained stable after the customary four cycles of initial chemotherapy. In typical practice, those patients would not be treated again unless their tumors resumed growing.

But in the trial, some patients got Alimta immediately after completing the initial, or first-line, chemotherapy. They lived a median of 13.4 months, significantly longer than the 10.6 months for those who got a placebo. And patients with the type of tumor for which Alimta works best lived a median of 15.5 months with maintenance therapy.

“This will change the treatment paradigm,” said Dr. Chandra P. Belani, deputy director of the Penn State Hershey Cancer Institute and the lead investigator in the trial.

But skeptics said the trial did not directly compare giving Alimta immediately with waiting until the tumor worsened. So it is not clear whether it was just the drug that provided the benefit, rather than the maintenance therapy. Two-thirds of the patients in the placebo group did get second-line therapy when their tumors worsened, but usually not with Alimta.

Alimta, also known as pemetrexed, costs about $4,000 per infusion given once every three weeks. Based on data from Lilly’s trials, patients getting the drug as maintenance therapy would receive an average of three more infusions than those getting the drug as second-line therapy.

Also, about 30 to 50 percent of lung cancer patients never get second-line chemotherapy, often because their condition worsens too much. So if Alimta were used as maintenance therapy, many more patients would get it.

For non-Hodgkin’s lymphoma, the drug used for maintenance is usually Rituxan, or rituximab, which is sold by Genentech and Biogen Idec.

A clinical trial showed that maintenance therapy with Rituxan did not help patients with an aggressive form of the disease. But a separate study, published recently in The Journal of Clinical Oncology, showed that it helped those with less aggressive forms of the disease.

After three years, cancer had not worsened for 68 percent of those who received the maintenance therapy. That was true for only 33 percent of those who did not receive the therapy. The survival difference was smaller, with 92 percent of those who got the maintenance therapy alive after three years compared with 86 percent of those who did not.

“We need more follow-up to see if it will improve overall survival,” said Dr. Thomas M. Habermann of the Mayo Clinic, an author of the study. Nevertheless, many doctors are giving patients maintenance treatment, usually four weekly infusions of Rituxan every six months for two years. That would cost about $30,000 a year.

For multiple myeloma, the drug being tried most often for maintenance therapy – Revlimid, or lenalidomide – is already being used for patients with relapses. It costs more than $6,000 a month and is taken as a once-a-day pill, making it particularly convenient for long-term use.

Right now it is used for an average of 10 months in the United States; with maintenance therapy that could grow to years, since remissions for multiple myeloma can last that long.

Trials are under way, but some doctors are not waiting. “We really need some randomized data to support it, but in the meantime it seems like a good idea,” said Dr. Brian G. M. Durie, chairman of the International Myeloma Foundation, an advocacy and research group that gets some financing from pharmaceutical companies.

Kevin, a graduate student with multiple myeloma, says he hoped a stem cell transplant would mark the end of his treatment. So he was taken aback when his doctor suggested taking Revlimid for two years as maintenance therapy as part of a clinical trial. He has been taking it a year so far, with some mild side effects like fatigue and upset stomach.

“I’m not enthusiastic about being on a drug like this indefinitely,” said Kevin, who spoke on the condition that his last name not be used because he did not want prospective employers to know about his illness. “But on the other hand, it’s a lot better than relapse.”

20091029-3

Ryan Collrd for The New York Times
RESEARCHER Chandra P. Belani led a lung cancer therapy clinical trial.

20091029-4

Brian Lee for The New York Times

Chuck Stauffer’s insurance covered hardly any of the cost of the cancer pills the doctor prescribed for him to take at home. 

 

By ANDREW POLLACK For The New York Times

Chuck Stauffer’s insurance covered the surgery to remove his brain tumor. It covered his brain scans. And it would have paid fully for tens of thousands of dollars of intravenous chemotherapy at a doctor’s office or hospital.

But his insurance covered hardly any of the cost of the cancer pills the doctor prescribed for him to take at home. Mr. Stauffer, a 62-year-old Oregon farmer, had to pay $5,500 for the first 42-day supply of the drug, Temodar, and $1,700 a month after that.

“Because it was a pill,” he said, “I had to pay – not the insurance.”

Pills and capsules are the new wave in cancer treatment, expected to account for 25 percent of all cancer medicines in a few years, up from less than 10 percent now.

The oral drugs can free patients from frequent trips to a clinic to be hooked to an intravenous line for hours. Fewer visits might save the health system money as well as time. And the pills are a step toward making cancer a manageable chronic condition, like diabetes.

But for many patients, exchanging an I.V. bag for a pill is a lopsided trade because the economics and practice of cancer medicine have not caught up with the convenience of oral drugs.

Start with the double ledger of drug insurance. Drugs that are infused at a clinic are typically paid for as a medical benefit, like surgery. Pills, though, are usually covered by prescription drug plans, which are typically much less generous; for expensive cancer pills, patients might face huge co-payments or quickly exceed an annual coverage limit. Sometimes, as in Mr. Stauffer’s case, a single insurer is involved.

Many times, though, a separate company – a so-called pharmacy benefit manager – provides the prescription drug coverage.

The growing use of cancer pills is also thrusting patients and doctors into new roles they have not yet fully mastered. Without a physician’s direct supervision, side effects can be missed. Some patients do not take all their medicine, raising the risk their cancer will worsen. Others take too many pills, risking toxic reactions.

For doctors, the new drugs also pose financial challenges. Physicians can profit from infusing drugs in their offices but not from writing prescriptions that are filled at a pharmacy.

With oral cancer drugs, “the technology has outstripped the ability of society to integrate it into the mainstream in a smooth fashion,” said Carlton Sedberry, a pharmacy expert at Medical Marketing Economics, a consulting firm.

Oregon, partly in response to Mr. Stauffer’s case, has passed a law requiring insurance companies to provide equivalent coverage of oral and intravenous cancer drugs. Some other states are now considering similar measures.

So far the health reform debate in Washington has not drilled into specifics like cancer pill coverage.

Infused drugs, of course, can also be frightfully expensive and under some insurance plans – including Medicare – can carry big co-payments. But it is the oral drugs that seem to be causing a disproportionate number of financial problems for cancer patients. The Patient Advocate Foundation, an organization that helps people make insurance co-payments for cancer drugs, says oral medicines accounted for 56 percent of the cases in which it helped Medicare patients last year, even though far more cancer patients were on intravenous drugs.

One oncology practice in central Pennsylvania has a nurse assigned full time to dealing with patients on oral drugs and arranging insurance or charity payments for the pills. “Trying to obtain this drug for the patient – that’s my struggle, every single day,” said the nurse, Jane Flenner.

Although drug makers are developing oral versions of some infused cancer medications, most of the new pills and capsules have no intravenous equivalent.

The oral exemplar is Gleevec from Novartis, which since its approval in 2001 has helped turn chronic myeloid leukemia as well as gastrointestinal stromal tumors into manageable diseases for many patients.

Douglas Jenson, 75, of Canby, Ore., has taken Gleevec for 10 years for leukemia. He goes for a blood test once every three months and sees his oncologist every six months, but is healthy enough to go whitewater rafting.

Making it even easier, Mr. Jenson gets his Gleevec free because he participated in an early clinical trial of the drug. Otherwise it would cost more than $40,000 a year.

While Mr. Jenson has been diligent about taking his five capsules every day at lunchtime, research indicates that many patients on the oral drugs do not consistently take the proper dose. One study, for example, found that Gleevec patients, on average, were taking only 75 percent of their prescribed doses.

Some cancer patients skip pills or stop taking them completely – whether because of costs, forgetfulness, side effects, complicated regimens or other factors.

“When I first started looking into this, I thought, ‘People with cancer have too much to lose, how can they not take their drugs?’ ” said Dr. Ann Partridge, an oncologist at Dana-Farber Cancer Institute in Boston.

Some other cancer patients, meanwhile, end up taking too many pills.

Gayne Ek of Allen, Tex., said he once skipped all of his Gleevec capsules for six weeks. Then, with the stockpile of capsules he accumulated, he took twice the prescribed dose for six weeks, hoping it would be more effective. It was not.

For many patients, though, the main challenge is not taking their pills, but paying for them. Under Medicare, most oral cancer drugs are covered by the Part D prescription drug program, which has a 25 percent co-payment. It also has the annual “doughnut hole” – reached when a patient’s total drug costs hit $2,700, after which the patient must shoulder the next $3,000 or so before coverage resumes.

Mary Francis Thomas of Camp Hill, Pa., reached the doughnut hole on her very first prescription of the year. Ms. Thomas, 86, had to pay $4,300 in January for a month’s supply of Revlimid, to treat a disorder that can lead to leukemia. Having now passed through the doughnut hole, she must pay 5 percent of the cost of the drug for the rest of the year – which still works out to $377 a month.

Drug companies say they provide free drugs for some patients and give money to charities for co-payment assistance. And Lee Newcomer, senior vice president for oncology at UnitedHealthcare, the big insurer, said many commercial policies capped total annual out-of-pocket expenditures, so patients should not have huge co-payments month after month.

But nurses and patient advocates say that many patients still have trouble paying for the drugs.

Mr. Stauffer, the Oregon farmer, is no longer one of them, though. After his daughter, Heather Kirk, told his story to Peter Courtney, the president of the state senate, Oregon enacted in late 2007 the nation’s first state law requiring insurers to provide equivalent reimbursement for oral and intravenous chemotherapy drugs.

Mr. Stauffer’s insurer, Regence Blue Cross Blue Shield, even reimbursed him for the money he had already spent on Temodar. Several other states, including Colorado, Hawaii, Minnesota, Montana, Oklahoma and Washington, are now considering similar legislation.

By NICHOLAS BAKALAR  For The New York Times

If you think your doctor will automatically tell you if you have an abnormal test result, think again. Researchers studying office procedures among primary care physicians found evidence that more than 7 percent of clinically significant findings were never reported to the patient.

The scientists, led by Dr. Lawrence P. Casalino, an associate professor at Weill Cornell Medical College, reviewed the records of 5,434 patients at 19 independent primary care practices and four based in academic medical centers. They extracted records that contained abnormal results for blood tests or X-rays and other imaging studies, and then searched for documentation that the patient had been properly informed of the problem in a timely way.

Then they surveyed the doctors with uninformed patients. Some told them that the patient had been informed, even though there was no documentation, while others believed the results were not significant and therefore required no notification. In a few cases, the doctor said that the patient had not yet been informed but soon would be. After accounting for these and other ambiguous cases, the researchers found that of 1,889 abnormal results, there were 135 failures to inform.

Results varied widely among the primary care practices, and all but the smallest – those with fewer than eight doctors – had at least one failure. In two of the largest academic medical centers, with a combined 80 primary care specialists, 23 percent of abnormal results were never mentioned to the patients.

Dr. Eric G. Poon, director of clinical informatics at Brigham and Women’s Hospital in Boston, who was not involved in the work, said it was a high-quality study with good methodology. “You go to the doctor and you get tests and assume that there is a right way for the doctor to look at the results and to act on them quickly,” he said. “But the truth of the matter is that a lot of things can fall through the cracks. Information is handed down from one person to another to another before the doctor actually sees it.”

Unsurprisingly, practices that used electronic medical records had lower failure rates than those that used only paper documents. But offices that used a combination of paper and computer records had the worst results of all.

Using information from a study of the literature and an earlier pilot study, the authors concluded that following five relatively simple procedures could eliminate most errors: results are routed to the responsible doctor, the doctor signs off on them, the office informs patients of all results, the practice documents that patients have been informed, and finally patients are told to call after a certain time interval if they have not learned the results of their tests. Most practices examined in the current study, published Monday in The Archives of Internal Medicine, failed to follow those steps.

The authors acknowledge that their sample was self-selected – offices volunteered to participate – and included only 23 practices. A random sample of offices, or a larger number of them, they write, could have produced different results.

Although some doctors may have informed their patients without documenting it, Dr. Casalino said that failure to document is almost as bad as failing to inform. “If what happens doesn’t get documented,” he said, “it can be very confusing when the patient next needs to be taken care of.”

For patients, Dr. Casalino said, the message is simple. “Don’t assume that ‘no news is good news’ when you have tests done. That’s a very dangerous assumption. If you’ve had a test done and you don’t hear about it after a week or two goes by, call the doctor’s office.”