Surgery is the standard treatment for most patients with colorectal cancer, followed by chemotherapy for those with more advanced disease. Adjuvant chemotherapy, as it’s called, helps lower the risk of the cancer coming back. According to the National Cancer Institute, about 30 percent of patients with stage 3 colon cancer who’ve had their tumor surgically removed experience a recurrence.

Traditionally, the standard of care for these patients was a combination of chemotherapy drugs called FOLFOX. When oncologists prescribe chemotherapy, they usually prescribe two or more medications, not a single drug. Each medication works in a different way, so a combination of drugs increases the likelihood that they’ll effectively kill cancer cells.

FOLFOX is a combination of two older drugs, fluorouracil and leucovorin, along with a newer drug, oxaliplatin. “[This combination] is highly effective at increasing CRC survival,” says Dr. Alok Khorana, director of the Gastrointestinal Malignancies Program at Cleveland Clinic. The standard of care is to give FOLFOX for six months.

“The problem with this combination is that it can cause severe neuropathy,” says Dr. John Strickler, a medical oncologist at Duke Health. Peripheral neuropathy is a tingling or numbing sensation in the hands or feet. Sometimes, it goes away once a patient completes treatment; for others, it can be permanent, Strickler says. “The more chemo you have, the more your risk of neuropathy goes up.”

[See: 8 Questions to Ask Your Doctor About Colon Cancer.]

Khorana says that for about 10 to 15 percent of patients, neuropathy can be painful and debilitating. “It can affect their quality of life. It’s meaningful, it’s not insignificant.”

A large international clinical trial with about 13,000 patients tried to determine if three months of FOLFOX would be just as effective as six months. If so, patients would have less risk of neuropathy and other side effects without compromising their five-year survival rate or risk of recurrence. Researchers presented results from the clinical trial (called CALGB-80702) in June at the American Society of Clinical Oncology 2017 Annual Meeting.

The clinical trial showed that, for the most part, three months was not as effective as six months. However, the results were nuanced.

Khorana says the researchers designed the trial so that if there was an up to 12 percent increased risk of cancer recurring or the patients dying from their cancer in the three-month group of patients compared to the six-month group, it met the goals of the study. In other words, the six-month and three-month regimens were comparable in terms of outcomes. They found, however, that there was an up to 15 percent increased risk of recurrence. This means they did not meet their predefined endpoints, or criteria for defining success.

Khorana says the researchers then divided the participants into two subgroups — high and low risk — based on their tumor types, and they found that for the higher risk group (those whose tumors were more likely to recur), six months of FOLFOX clearly seemed better.

The specifics of clinical trial design, such as whether the researchers create subgroups before the trial begins or after they collected the data, is more detail than the average patient needs to know. However, these details are important to clinicians, who must interpret the results and determine if it makes sense to change the way they prescribe treatments.

“The results [of this clinical trial] are complex,” Strickler says. “We’re still trying to digest it and incorporate it into our practice.”

[See: 10 Ways to Prepare for Surgery.]

And there’s another wrinkle in the analysis. Oncologists can prescribe these drugs one of two ways: Patients either receive FOLFOX intravenously or take a comparable pill version called CapeOx (a combination of capecitabine and oxaliplatin). In terms of outcomes, the pill version is equivalent to the infusion version. Which version a patient gets really depends on individual physician practice patterns.

However, Khorana says, in the clinical trial, for patients who got the pill version, the three-month regimen was better — so much so that there’s no clear outcome difference in three months versus six months. He cautions that this finding was also an after-the-fact observation, not part of the initial study design, so it may not account for other factors that introduce uncertainty into the findings.

So, what does this mean for patients with stage 2 colorectal cancer?

“We want to make sure patients get what they need [in terms of treatment] and nothing more,” Strickler says. “Up until now, we were not able to stop at three months. We did not know if it was safe.” The absolute difference in outcomes between three and six months is small, but the difference in side effects is significant.

[See: 10 Seemingly Innocent Symptoms You Shouldn’t Ignore.]

“If patients start getting bad neuropathy, we can stop at three months in patients with a good prognosis,” Khorana says. “In higher risk patients, they definitely need six months.” If patients fall somewhere in between, they can have a discussion with their physician about the risks and benefits of continuing for six months. “It’s a more nuanced discussion,” he says.

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A Shorter Course of Chemotherapy May Lessen Side Effects for Some Colon Cancer Patients originally appeared on usnews.com