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So here's an IDEA: Trim colon cancer chemo time without efficacy sacrifice


By Randy Osborne
Staff Writer

CHICAGO – New research has given the nod for cancer doctors to cut in half the term of chemotherapy for those with lymph node-positive (stage III) tumors, thus sharply reducing the toll taken on patients in the forms of nerve damage, diarrhea and fatigue.

"The question is, of course, 'How much loss of antitumor efficacy would we be willing to compromise for much better toxicity outcomes?'" said senior study author Axel Grothey from the Mayo Clinic Cancer Center in Rochester, Minn. "How much are we willing to push patients into six months of therapy for a very minimal difference [in efficacy]?"

They needn't be pushed so hard, apparently. Pointing out that such research is funded by philanthropy and the likes of the NIH, Grothey posed another rhetorical question: "Who's interested in shortening the duration of therapy from a commercial perspective?" The study was funded by grants from the NIH, Medical Research Council, National Cancer Institute, Italian Agency for Drugs, Japanese Foundation for Multidisciplinary Treatment of Cancer, French Ministry of Health and the French National Cancer Institute.

In an analysis of six clinical trials that enrolled more than 12,800 patients, three months of chemotherapy proved nearly as effective as six months in those with relatively lower recurrence risk. The shorter term caused fewer side effects, too, especially nerve damage brought by oxaliplatin. Chemo is known to lower the odds of recurrence after colon cancer surgery, and since 2004, the standard (adjuvant) treatment after surgery has been a combination of chemo regimens – FOLFOX or CAPOX – given over a period of six months. Investigators wanted to find out if three months might work just as well.

Specifically, the study pooled data from six experiments conducted in North America, Europe and Asia. While the primary endpoint was not proved statistically, a shorter, three-month course of chemo turned up a less than 1 percent lower chance of being colon cancer-free at three years compared to the standard six-month ordeal (74.6 percent vs. 75.5 percent). In patients considered at low risk of cancer recurrence – 60 percent of the total examined – the difference was even smaller (83.1 percent in three-month patients vs. 83.3 percent in six-month patients).

The findings could apply to about 400,000 people with colon cancer worldwide every year. For the 60 percent with lower risk that their disease will return, three months of chemo is likely to become the new standard of care.

The study is a prospective, pre-planned analysis of results from the half-dozen phase III trials conducted in 12 countries, undertaken by way of an approach established more than 10 years ago as the IDEA (International Duration Evaluation of Adjuvant therapy) collaboration. A steering committee oversaw the study design, and an independent statistical center reviewed the results from all six trials. At the time IDEA began in 2007, it wasn't possible to run a single study of the size needed anywhere in the world.

Patients were followed for a median time of 39 months. The type of chemo regimen selected by doctors affected the difference in three-year disease-free survival between the three-month and six-month treatment durations, though the difference was fairly small in both cases (75.9 percent vs. 74.8 percent with CAPOX and 73.6 percent vs. 76 percent with FOLFOX). The rate of clinically meaningful (grade 2 or greater) nerve damage also differed depending on the regimen, but was consistently higher for people who received six months vs. three months of chemo (45 percent vs. 15 percent with FOLFOX and 48 percent vs. 17 percent with CAPOX).

"This is a great day for patients throughout the world," said ASCO expert Nancy Baxter. "What we've heard today is practice-changing work. Less is more."

She emphasized the seriousness of the nerve damage that some patients undergo – numbness of the hands and feet, sometimes lasting for the rest of their lives. "This type of [research] can only be done with federal funding," she added, echoing Grothey. "The pharmaceutical industry is not interested in giving less treatment."

Overall, the findings are viewed as another step on the road to devising more sophisticated treatments tailored to the needs and risk profiles of individual patients.