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In Reply:

¹ Dalhousie University, Halifax, Nova Scotia, Canada

S. Jane Darnton², Venice Archer², David Ferry²

² Birmingham Heartlands Hospital, Birmingham, UK

Deborah Stocken³, Paul Mulholland³

³ Cancer Research UK, Trials Unit, Institute of Cancer Research, University of Birmingham, Birmingham, UK

Dr Kraut has called to our notice the early contributions of the Detroit group to the multimodality treatment of esophageal cancer. Their observation linking pathological complete response (pCR) after neoadjuvant chemoradiotherapy with improved survival, has been borne out by many phase II studies; however, despite encouraging pCR rates (24% on pooled data),¹ the combined approach has not led to improvements in survival in subsequent randomized trials,² Forastiere et al² reported that only 24% of their pCR patients were alive at 5 years. What is important to appreciate about the chemoradiotherapy trials is that the chemotherapy regimens used were not good enough to deliver long-term systemic control and therefore failed to have a major impact on the natural history of the disease.

Our article³ analyzed the results of two previous phase II trials of low toxicity neoadjuvant chemotherapy, without radiotherapy, with a follow-up of at least 6 years. The median survival of nine (14%) of 66 pCR cases had not been reached, and seven of the nine pCR cases were alive and disease-free at that stage. We therefore felt justified in stating in our title that "pathologic complete response induced by chemotherapy leads to long-term survival." The passage of time has confirmed that conclusion. Of the seven pCR patients alive at the time of report, one died at age 74 years at 13 years 5 months after surgery of ischemic heart disease, and six patients are still alive, with follow-up ranging from 9 years 7 months, to 13 years 6 months.

We agree that, as in all of medicine, we continue to build on the accomplishments of our predecessors. However, large randomized trials are still needed to establish optimal multimodality treatment for this aggressive disease. We hope that others will see the virtue of achieving high pCR rates with chemotherapy alone as the marker that is most likely to correlate with long-term survival and cures.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Geh J, Crellin A, Glynne-Jones R: Preoperative (neoadjuvant) chemoradiotherapy in oesophageal cancer. Br J Surg 88:338–356, 2001[CrossRef][Medline]

2. Forastiere A, Orringer M, Perez-Tamayo C, et al: Preoperative chemoradiation followed by transhiatal esophagectomy for carcinoma of the esophagus: Final report. J Clin Oncol 11:1118–1123, 1993[Abstract/Free Full Text]

3. Darnton SJ, Archer VR, Stocken DD, et al: Preoperative mitomycin, ifosfamide, and cisplatin followed by esophagectomy in squamous cell carcinoma of the esophagus: Pathological complete response induced by chemotherapy leads to long-term survival. J Clin Oncol 21:4009–4015, 2003[Abstract/Free Full Text]

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• Preoperative Mitomycin, Ifosfamide, and Cisplatin Followed by Esophagectomy in Squamous Cell Carcinoma of the Esophagus: Pathologic Complete Response Induced by Chemotherapy Leads to Long-Term Survival
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