Cause For Concern Too Many Cancer Patients Receive Inadequate Chemotherapy Doses

A national body of oncology researchers has uncovered an uncomfortable finding: about one-third of patients with potentially curable breast cancer aren’t receiving full-strength doses of chemotherapy because of their fear of side effects or problems related to their care.


Now, the American Society of Clinical Oncology (ASCO) is seeking to discover whether this problem is prevalent with other cancers — and how seriously the practice can impact patients’ health and odds of survival.

“The bottom line is that nobody knows,” said Dr. Howard Ozer of the Oklahoma University Cancer Center, who is leading an ASCO effort to examine this trend. “It has not been recognized that this (under-dosing) is a problem.”

But doctors are aware of the issue, even if they don’t fully understand its long-term impact, said Dr. Wilson Mertens, medical director of Cancer Services at Baystate Medical Center.

“There are a number of ways the oncology community has tried to deal with this problem,” he said. “There’s a natural human tendency to cut corners and say, ‘I’m so smart, and I know how to do it better and more efficiently.’

“But for me, the most critical part is the implemen-tation of chemotherapy regimens in patients with curable cancers — lymphoma, early breast cancer, now early lung cancer,” he continued. “Using the data and studies we have, these regimens are more effective than ever before, but the only way to achieve those results is to do exactly what those studies suggest, and that’s where things can get a little sloppy.”

In a worst-case scenario, many doctors fear, sloppy could turn deadly.

Alarm Bells

Dr. Larry Norton, deputy physician in chief for breast cancer at Memorial Sloan-Kettering Cancer Center, has produced research suggesting that undergoing chemotherapy for breast cancer every two weeks instead of every three can improve the survival rate by 30{06cf2b9696b159f874511d23dbc893eb1ac83014175ed30550cfff22781411e5} — which implies that skipping or lowering doses can pose deadly risks. “We’re very concerned about it,” he said.

Dr. Gary Lyman of the University of Rochester Medical Center said the low-dose phenomenon is not limited to breast cancer. Indeed, two studies unveiled at ASCO’s annual scientific meeting in New Orleans show that standard chemotherapy markedly improves survival in victims of early-stage lung cancer.

Scientific studies have traditionally determined the accepted dose levels and frequencies in chemotherapy treatment. But studies suggest that community oncologists in particular don’t heed such recommendations as strictly as researchers suggest.

For example, Lyman reviewed the medical records of some 20,000 breast cancer patients who underwent post-surgery chemotherapy. He discovered that more than half of them received less than 85{06cf2b9696b159f874511d23dbc893eb1ac83014175ed30550cfff22781411e5} of the optimal dose intensity. For one-quarter of these patients, the main problem was postponing chemo sessions, but for the rest, it was insufficient dosage.

Mertens cited a study published in the Journal of the National Cancer Institute that examined cure rates in community clinics against those achieved in comprehensive, well-integrated cancer programs.

“There was a difference of 15 or 20 percentage points, in terms of better outcomes, in larger programs that stick to the rules and know not to cut down doses,” he said. “This is not a small issue, but it’s particularly important for patients with curable malignancies.”

Lyman is quick to note that many women in his study were treated in the mid-1990s, before the advent of more easily tolerated chemotherapy agents. So he has begun examining the records of 10,000 women treated since 2000 — and finding some improvement, with about a third of patients undertreated.

Considering that only 5{06cf2b9696b159f874511d23dbc893eb1ac83014175ed30550cfff22781411e5} to 10{06cf2b9696b159f874511d23dbc893eb1ac83014175ed30550cfff22781411e5} of all patients truly cannot tolerate full doses, Lyman said, even those numbers are cause for concern.

Benefits at Any Age

One demographic that has not traditionally received high-dose chemotherapy is patients age 70 and older. But that could be changing as well.

“Some of that has to do with clinical judgments in terms of what patients will tolerate, but there is a bias against treating older patients,” Mertens said.

However, a French study recently published in the journal Cancer concluded that age cutoffs should not be the sole factor in making chemotherapy treatment decisions in cases of acute myelogenous leukemia (AML), a common cancer in elderly people that has a three-year survival rate of less than 10{06cf2b9696b159f874511d23dbc893eb1ac83014175ed30550cfff22781411e5}.

The 110 AML patients in the study, who all received similar chemotherapy treatment, had remission rates of 45{06cf2b9696b159f874511d23dbc893eb1ac83014175ed30550cfff22781411e5} in the over-75 group and 49{06cf2b9696b159f874511d23dbc893eb1ac83014175ed30550cfff22781411e5} among those 65 to 74 years old. Two-year survival rates were 27{06cf2b9696b159f874511d23dbc893eb1ac83014175ed30550cfff22781411e5} for those over age 75 and 25{06cf2b9696b159f874511d23dbc893eb1ac83014175ed30550cfff22781411e5} in the 65-to-74 group.

Whatever their age or type of cancer, Mertens said, patients need to be sure they’re getting the proper dose.

“We see patients, and we look at the regimens that have been administered before, and we’re left scratching our heads, wondering, ‘where did they come up with this sloppiness in clinical care?’” he said.

“That’s why it’s important to have oncologists who specialize in a couple of diseases, know them cold, and know all the research going on, instead of taking on all the diseases. It’s important to stay current on everything and truly understand the side effects of all regimens and the appropriate dose reductions for those regimens.”

If the studies are to be believed, the medical community has some ground to make up in that regard.

Some material for this article was provided by the American Society of Clinical Oncology.

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