Esophageal Cancer Response to Chemo Apparent After 2 Weeks

Zosia Chustecka

January 20, 2011

January 20, 2011 — Scanning with positron emission tomography (PET) was useful in identifying patients with locally advanced adenocarcinoma of the esophagogastric junction who were responding to chemotherapy, and the response was apparent after 2 weeks of treatment.

This conclusion comes from the prospective MUNICON II study, the details of which were reported at a presscast ahead of the 2011 Gastrointestinal Cancers Symposium, cosponsored by the American Society of Clinical Oncology, among others.

"We confirmed that PET testing after 2 weeks of chemotherapy is a very important prognostic tool," said lead investigator Florian Lordick, MD, PhD, from the Klinikum Braunschweig in Brunswick, Germany.

"This approach can help a physician distinguish patients who are responding to chemotherapy from those who are not, and who can therefore be spared from the unnecessary toxicities of a treatment that is unlikely to improve their outcome" he added.

Poor Prognosis

Esophageal cancer generally has a poor prognosis, Dr. Lordick noted. Preoperative chemotherapy is recommended, but only some of the tumors respond. Benefits are confined to patients who do respond; the others derive little benefit but experience the adverse effects of therapy, he explained. The problem lies in identifying the patients who are responding to treatment, he said.

In this study, PET imaging with fluorodeoxyglucose (FDG) was used to detect glucose uptake by the tumor, which is a sign of tumor proliferation. When tumors respond to chemotherapy, they stop growing and a sharp decrease in glucose uptake can be seen on the FDG-PET scan.

The study looked at 56 patients with locally advanced esophagogastric cancer (median age, 62 years; 91% male). All patients had FDG-PET scans before and 2 weeks after chemotherapy (a platinum compound and 5-flurouracil).

After 2 weeks, 23 of 56 patients (41%) who were found to be not responding to chemotherapy had their treatment intensified; they underwent radiotherapy (32 Gy) and were given daily cisplatin (6 mg/m2). "The expectation was that adding radiation would improve survival," Dr. Lordick said. Unfortunately, this did not prove to be the case, he continued. Despite the extra therapy, this group had worse outcomes than the 33 of 56 patients (59%) who were found on PET to be responding.

Of the 33 patients who responded to chemotherapy, 27 (82%) underwent curative surgery; of the 23 who did not responded to chemotherapy, only 16 patients (70%) underwent curative surgery. Major histologic remissions (<10% residual tumor) were observed in 12 of the responders (36%) and in 6 of the nonresponders (26%).

After a median follow-up of 38 months, median event-free survival was 15.4 months and overall survival was 18.3 months for the nonresponders; these outcomes have not yet been reached by the responders, Dr. Lordick reported.

"What's unfortunate is that the results of our study also indicate that for early metabolic nonresponders, there is not yet an effective salvage treatment that could improve their poor prognosis," he explained.

We are continuing to look for more effective ways to treat this group of patients," he said, adding that future trials will test different chemotherapy regimens and novel biologic agents.

"This study is quite intriguing," said Jennifer Obel, MD, from NorthShore University Health System in Evanston, Illinois, who moderated the presscast. This is an example of "what we are doing now in oncology, looking for early indicators of responses to therapy," she said.

These can be molecular markers, such as the KRAS testing to indicate which patients are likely to benefit from epidermal growth-factor receptor inhibitors, or can involve imaging, such as the PET scans used in this study. Here, the PET scan indicated very early which patients were not responding to chemotherapy; this allows the treating clinician to try a different approach, which might offer greater benefit for these patients, she said.

The authors have disclosed no relevant financial relationships.

2011 Gastrointestinal Cancers Symposium (GICS): Abstract 3. To be presented January 20, 2011.


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