When to change the course of treatment

Counting circulating tumor cells before and after the start of treatment for patients with metastatic colorectal cancer could help doctors determine when or if a change in treatment should be made.

The results of a large, multicenter, international study laying the groundwork for such decisions were presented at the Annual Meeting of the American Society of Clinical Oncology. The study showed the number of circulating tumor cells, or CTC, is a significant predictor of survival and cancer progression.

Few studies have examined the relationship of CTC and a patient's prognosis in cancer. This is an important area of research in metastatic colorectal cancer because there are little data to help physicians chose which treatment is best for which patients or to determine when a change in treatment is warranted.

"If we had a way to know early on that a tumor isn't responding to a particular drug, we could switch to a different treatment before growth of the cancer is seen on a CAT scan," said Neal J. Meropol, director of the gastrointestinal cancer program at Fox Chase Cancer Center and lead investigator of the study. "If we could determine that the tumor was destined to grow after a few weeks of treatment, we'd be able alter course even before the first scan."

For this study, Meropol and his colleagues examined the association between the circulating tumor cell number and progression-free and overall survival for 430 adult patients with metastatic colorectal cancer.

The number of CTC was measured at baseline, one month, and several other points after the start of treatment. CTC were isolated and counted by an immunomagnetic cell separation technique, an FDA-approved technology developed by Immunicon Corporation (Nasdaq-Global Market: IMMC}. CT scans were obtained in usual practice,at baseline and every 6-12 weeks after starting treatment.

Having 3 or more CTC (per 7.5 mL of blood) was defined as "unfavorable" in an initial analysis. Patients with fewer than 3 CTC were considered favorable.

Before initiation of the first treatment (baseline), 53 percent of patients had no detectable CTC. These patients had superior median survival times compared with those patients who had circulating tumor cells. A favorable CTC number before treatment is associated with better progression free survival and overall survival.

In addition to its predictive value at baseline, the CTC was also a strong indicator of prognosis as early as 3-5 weeks after treatment initiation.

"Patients with unfavorable CTC had a shorter median survival time. This was even seen in those patients whose CT scan , the gold standard for tumor evaluation- indicated no disease progression," Meropol explained.

The median overall survival of patients with a favorable CTC before treatment was almost double that of those with an unfavorable CTC (18.5 months vs. 9.4 months). Patients with a favorable CTC had a median progression free survival of 7.9 months and those with an unfavorable CTC had a progression free survival of 4.5 months. The measurement of CTCs consistently provided prognostic information even when tested at 6-12 weeks.

Another key finding was the predictive value of a change in CTC. Among patients with unfavorable CTC at baseline, those whose numbers decreased after treatment to fewer than 3 had improved progression-free survival and overall survival.

"Potentially, this tool could be useful in the clinic to make real-time decisions about whether a treatment is helping. Our ultimate goal is to continue effective treatment, but spare patients the side effects of a treatment that is destined to fail. This is the direction that future studies must take"