Comparison of Chemotherapy Regimens in Metastatic Esophageal and Gastroesophageal Junction Adenocarcinoma

Key Points

  • FOLFOX performed best overall compared with ECF and irinotecan/cisplatin in patients with previously untreated metastatic esophageal or gastroesophageal junction adenocarcinoma.
  • Irinotecan/cisplatin appeared to be associated with poorer efficacy and greater toxicity.

FOLFOX (oxaliplatin, leucovorin, fluorouracil [5-FU]) seems to be a safer and more reliable regimen than ECF (epirubicin, cisplatin, 5-FU) and irinotecan/cisplatin as a backbone for treatment in future studies of metastatic esophageal and gastroesophageal junction cancers. This finding from the phase II CALGB (Cancer and Leukemia Group B) 80403 (Alliance)/E1206 study was reported by Enzinger et al in the Journal of Clinical Oncology.

Cetuximab (Erbitux) was added to each treatment on the basis of promising preclinical data. However, as stated by the investigators, based on findings since the current study was initiated, it appears “unlikely that cetuximab inflated the [response rates] or the survival of the platinum/fluorouracil-based regimens tested in our study.” The potential for molecular characteristics to predict benefit or lack of benefit from cetuximab is currently being assessed in a correlative analysis of study samples.

Study Details

In CALGB 80403 (Alliance)/E1206, 222 patients with previously untreated metastatic esophageal or gastroesophageal junction adenocarcinoma were randomized between September 2006 and May 2009 to receive ECF, irinotecan/cisplatin, or FOLFOX—all with cetuximab once weekly. The primary endpoint was response rate.

Outcomes

Response rates were 60.9% in the ECF group, 45.0% in the irinotecan/cisplatin group, and 54.3% in the FOLFOX group. Median overall survival was 11.6, 8.6, and 11.8 months; median progression-free-survival was 7.1, 4.9, and 6.8 months; and median time to treatment failure was 5.6, 4.3, and 6.7 months, respectively.

The FOLFOX group had a lower rate of treatment modification (73% vs 85% and 91%, P = .013) and a lower rate of treatment discontinuation due to adverse events or treatment-related death (11% vs 19% and 26%, P = .17).

The investigators concluded: “[O]n the basis of the favorable efficacy of ECF-[cetuximab] and FOLFOX-[cetuximab] and the superior tolerability of FOLFOX-[cetuximab], FOLFOX seems to be the safer and more reliable chemotherapy backbone for future testing in cooperative group studies in advanced esophageal and [gastroesophageal junction] cancers. However, selection of future chemotherapy plus targeted agent combinations will ultimately depend on the unique characteristics and interactions of the specific agents involved. Findings of this study suggest that FOLFOX represents an attractive standard of care for treatment of patients with advanced esophageal cancer.”

The study was supported by the National Cancer Institute, the National Institutes of Health, ImClone Systems/Bristol-Myers Squibb, Pfizer Oncology, and Sanofi.

Peter C. Enzinger, MD, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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