ECOG 2205: Trial stopped due to pulmonary toxicity in operable esophageal adenocarcinoma

Issue: November 25, 2010

52nd ASTRO Annual Meeting

SAN DIEGO — Neoadjuvant oxaliplatin, 5-FU plus cetuximab and concurrent radiation for the treatment of operable adenocarcinoma of the esophagus demonstrated promising activity based on pathologic complete response, but pulmonary toxicity was significant, leading to closure of the phase 2 ECOG trial.

The researchers conducted the trial to determine whether the addition of cetuximab (Erbitux, ImClone) to neoadjuvant preoperative therapy potentially improved the pathologic complete response rate from 25% to 45%. There were 22 patients enrolled when the trial closed due to toxicity.

Chemoradiotherapy consisted of oxaliplatin 85 mg/m² on day 1, 15 and 29; infusional 5-FU 180 mg/m² every 24 hours for 35 days; plus cetuximab 400 mg/m² on day 1, then 250 mg/m² on days 8, 15, 22 and 29 and radiation 180 cGy/day for 25 fractions (Monday through Friday). Intensity-modulated radiotherapy was permitted. Lung dosing guidelines limit the proportion of lung receiving 20 Gy to 20% and at least 10 Gy to 40%.

Eighteen patients had surgery. Thirty-two percent of patients had pathological complete response. Thirteen patients started adjuvant chemotherapy; 12 completed therapy. There were four postoperative deaths due to adult respiratory distress syndrome (ARDS). Two of seven patients with complete response died of ARDS.

There was no suggestion of a relationship between ARDS and radiation technique. Among four patients with ARDS, the volume of lung getting 5% of the prescribed dose was 46%, 55%, 65% and 72%, and the volume getting 20% of the dose was 17% in three patients and 19% in the fourth. For all patients, the median volume of lung getting 5% was 50% and the median volume of lung getting 10% was 11%.

Fifteen patients were treated within the more restrictive radiotherapy guidelines of the prior trial, E1201, in which no patients had postoperative ARDS. Neoadjuvant therapy was CPT-11/cisplatin/radiotherapy or paclitaxel/cisplatin/radiotherapy, with typically no more than three to four radiotherapy fields, lung 2 cm outside the target less than 40 Gy and no intensity-modulated radiotherapy. In the current trial, three of 15 patients who met the criteria of the prior study had ARDS, according to the researchers.

“We hope that more information will be available from these ongoing trials that use cetuximab, so we can see if that plays a role,” Lawrence R. Kleinberg, MD, associate professor of radiation oncology and molecular radiation sciences at The Johns Hopkins Hospital, in Baltimore, said during a presentation. – by Christen Cona

For more information:

Kleinberg L. Abstract #154. Presented at: 52nd ASTRO Annual Meeting; Oct. 31-Nov. 4, 2010; San Diego.

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