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

Abstract

BackgroundPatients 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.MethodsThis 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/m2 plus irinotecan 65 mg/m2 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.ResultsForty 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.ConclusionsThe 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 registrationClinicaltrials.gov: NCT00137852, registered August 29, 2005.

The prognostic value of cyclooxygenase-2 expression in patients with esophageal cancer: evidence from a meta-analysis

“…They found that the addition of celecoxib to neoadjuvant cisplatin–irinotecan chemoradiation was tolerable; the OS appeared comparable to prior studies using neoadjuvant cisplatin–irinotecan chemoradiation alone. 44 The further mechanism of anticancer effects of COX-2 inhibitors should be elucidated, and results from large randomized clinical trials are needed to provide useful information in further establishing the efficacy of COX-2 inhibitors in adjuvant chemotherapy.…”

Incidence of Brain Metastasis as First Event in Patients with Esophageal Carcinoma: a Report from Three Prospective Alliance Clinical Trials

“…In a prospective phase II trial of neoadjuvant chemotherapy followed by surgical resection in a contemporary group of 40 patients with esophageal cancer (85% with adenocarcinoma), Cleary et al reported that six patients (15%) developed brain metastasis at a median of 13.9 months after surgery [15]. In ve of the six patients, adenocarcinoma was the primary histology and brain was the rst site of metastasis in four of 40 patients (10%).…”

“…Notably, adenocarcinoma was the primary histology in all cases of brain metastasis. Subsequently, a prospective trial of neoadjuvant chemotherapy followed by surgical resection in a contemporary cohort of patients with esophageal carcinoma reported a similar incidence of brain metastasis of 15%, also noting a predominance of adenocarcinoma histology [15].…”

Biochemical control of the combination of cyclooxygenase‐2 inhibitor and 125I‐brachytherapy for prostate cancer: Post hoc analysis of an open‐label controlled randomized trial

“…The current study first elucidated the antitumor effect of the combination of COX-2 inhibitor and brachytherapy in patients with prostate cancer. Although no report has evaluated the antitumor effect of the combination of COX-2 inhibitor and radiation therapy in prostate cancer, the efficacy of combination therapy was evaluated in patients with rectal cancer, 17 non-small-cell lung cancer, 18,19 glioblastoma, 20 nasopharyngeal carcinoma, 21 esophageal cancer 22 and pancreatic cancer. 23 Decucquoy et al reported that patients with rectal cancer treated with radiation (45 Gy; 1.8 Gy/fraction) and celecoxib (800 mg/day; n = 18) as neoadjuvant therapy were more likely to have a better response (61%) than those treated with radiation and placebo (n = 17; 35%).…”