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Pathologic complete response may not represent the optimal surrogate for survival after preoperative therapy for esophageal cancer

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Abstract

Background

We designed a phase II trial to examine the benefit of preoperative hyperfractionated radiation therapy (XRT) and concurrent chemotherapy for patients with locally advanced esophageal cancer (LAEC).

Aim of Study

The pathologic complete response (pCR) was the primary endpoint to estimate efficacy.

Methods

Twenty-three patients with LAEC received twice-daily XRT during wk 1 and 5 once-daily XRT during wk 2–4 (59 Gy). Cisplatin (100 mg/m2) was given on d 1, while 5-fluorouracil (1000 mg/m2) was given by continuus infusion the first and fifth weeks of the XRT.

Results

The pCR for the 19 patients undergoing esophagectomy was 16%. The study was closed at the interim analysis having not met the required minimum pCR rate of 20%. Hematologic toxicities consisted of grades III and IV neutropenia observed in 33% and 14% of patients, respectively. Grade III nausea and vomiting was seen in 38% of patients. One grade V pulmonary toxicity occurred. The median survival was 44.6 mo with 65% of patients alive at 2 yr.

Conclusions

The pCR rate in this trial did not meet the predetermined statistical minimum. With the encouraging 2-yr survival, it is not clear that pCR is a reliable surrogate endpoint to discern treatment efficacy.

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Authors and Affiliations

  1. Division of Medical Oncology, Wake Forest University School of Medicine, Winston Salem, NC

    Mabea Aklilu & Susan A. Melin

  2. Department of Public Health Sciences, Wake Forest University School of Medicine, Winston Salem, NC

    James Lovato

  3. Division of Gastroenterology, Wake Forest University School of Medicine, Winston Salem, NC

    Girish Mishra

  4. Department of Cardiothoracic Surgery, Wake Forest University School of Medicine, Winston Salem, NC

    Timothy Oaks

  5. Department of Pathology, Wake Forest University School of Medicine, Winston Salem, NC

    Kim Geisinger

  6. Department of Surgery, Wake Forest University School of Medicine, Winston Salem, NC

    Edward A. Levine

  7. Department of Radiation Oncology, Wake Forest University, 27157, Winston Salem, NC

    A. William Blackstock & Michael R. Farmer

Authors
  1. A. William Blackstock
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  2. Mabea Aklilu
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  3. James Lovato
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  4. Michael R. Farmer
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  6. Susan A. Melin
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  7. Timothy Oaks
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  8. Kim Geisinger
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  9. Edward A. Levine
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Correspondence to A. William Blackstock.

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Blackstock, A.W., Aklilu, M., Lovato, J. et al. Pathologic complete response may not represent the optimal surrogate for survival after preoperative therapy for esophageal cancer. Int J Gastrointest Canc 37, 7–14 (2006). https://doi.org/10.1385/IJGC:37:1:7

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  • DOI: https://doi.org/10.1385/IJGC:37:1:7

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