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

  • A. William Blackstock
  • Mabea Aklilu
  • James Lovato
  • Michael R. Farmer
  • Girish Mishra
  • Susan A. Melin
  • Timothy Oaks
  • Kim Geisinger
  • Edward A. Levine
Research Article

DOI: 10.1385/IJGC:37:1:7

Cite this article as:
Blackstock, A.W., Aklilu, M., Lovato, J. et al. Int J Gastrointest Canc (2006) 37: 7. doi:10.1385/IJGC:37:1:7

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.

Key Words

Esophageal cancer pathologic complete response hyperfractionated radiation therapy 

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  • A. William Blackstock
    • 7
  • Mabea Aklilu
    • 1
  • James Lovato
    • 2
  • Michael R. Farmer
    • 7
  • Girish Mishra
    • 3
  • Susan A. Melin
    • 1
  • Timothy Oaks
    • 4
  • Kim Geisinger
    • 5
  • Edward A. Levine
    • 6
  1. 1.Division of Medical OncologyWake Forest University School of MedicineWinston Salem
  2. 2.Department of Public Health SciencesWake Forest University School of MedicineWinston Salem
  3. 3.Division of GastroenterologyWake Forest University School of MedicineWinston Salem
  4. 4.Department of Cardiothoracic SurgeryWake Forest University School of MedicineWinston Salem
  5. 5.Department of PathologyWake Forest University School of MedicineWinston Salem
  6. 6.Department of SurgeryWake Forest University School of MedicineWinston Salem
  7. 7.Department of Radiation OncologyWake Forest UniversityWinston Salem