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BMC Cancer. 2016 Jul 13;16:468. doi: 10.1186/s12885-016-2485-9.

Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer.

Author information

1
Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA.
2
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
3
University of Arizona Cancer Center, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
4
Center for Esophageal and Gastric Cancer, Dana-Farber Brigham and Women's Cancer Center and Gastrointestinal Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA. peter_enzinger@dfci.harvard.edu.

Abstract

BACKGROUND:

Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation.

METHODS:

This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery.

RESULTS:

Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases.

CONCLUSIONS:

The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted.

TRIAL REGISTRATION:

Clinicaltrials.gov: NCT00137852 , registered August 29, 2005.

KEYWORDS:

Chemoradiation; Cyclooxygenase 2 inhibition; Esophageal cancer; Neoadjuvant therapy

PMID:
27412386
PMCID:
PMC4944495
DOI:
10.1186/s12885-016-2485-9
[Indexed for MEDLINE]
Free PMC Article

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