Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

Abstract

Purpose The aim of this study was to evaluate the activity and safety of oxaliplatin/5-Xuorouracil-based chemo-radiotherapy in patients with not radically resectable locally advanced esophageal cancer. Methods Fifty-nine patients with adeno or squamous-cell carcinoma received oxaliplatin (60 mg/m 2 ), and leucovorin (20 mg/m 2 on days 1, 8,15,29,36,43,50,57) followed by continuous infusion Xuorouracil (200 mg/m 2 per day on days 1-22 and 29-64) with radiotherapy (1.8 Gy daily fractions to a total dose of 45 Gy, from days 29 to 64). When feasible, surgery was scheduled 6-8 weeks after chemoradiotherapy completion. The primary endpoint was 1-year progression-free survival. Results Forty (68%) patients completed treatment without modiWcations. An objective clinical response was seen in 35 patients (59%). Esophagectomy was possible in 33 patients and a complete resection (R0) was achieved in 26 (79%) with 6 pathologic complete responses (pCR) and 3 near pCR.At a median follow-up of 39.7 months for the surviving patients, the median progression-free and overall survivals were 11 months (95% CI 6.5-14) and 18.5 months (95% CI 13-29). The 1-year progression-free and overall survivals were 47.5% (95% CI 34-59.5%) and 63% (95% CI 49-74%). Major toxicities were esophagitis (20% G3 and 5% G4) and diarrhea (8.5% G3 and 8.5% G4). Hematological toxicity (7% G3 and 3% G4) was less common; severe neurotoxicity (3% G3) was infrequent. Conclusions Concurrent oxaliplatin, leucovorin, Xuorouracil and radiotherapy followed or not by esophagectomy has a tolerable toxicity and promising activity in locally advanced esophageal cancer.

Effect of Preoperative Chemoradiotherapy on Outcome of Patients with Locally Advanced Esophagogastric Junction Adenocarcinoma—A Pilot Study

“…In our series, toxicity was acceptable, with most adverse events being grade 1 or 2, and no treatmentrelated deaths being recorded. Dose reduction was required in 8 patients, and rates of grades 3 and 4 hematologic and nonhematologic toxicities were similar to those reported in other phase ii trials of preoperative crt (including oxaliplatin and 5fu-based chemotherapy) in esophageal or gej cancer [29][30][31][32] and also by our group in earlier work involving resected high-risk gastric cancer patients 13 . Those results are particularly interesting because our study used a higher radiotherapy dose than that reported in the German study (45 Gy vs. 30 Gy).…”

NEOSCOPE: A randomised phase II study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma

“…Single arm phase I–II studies have demonstrated feasibility of oxaliplatin-based nCRT [9], [10], [11], [12], [13], [14], [15]. One randomised phase II study comparing oxaliplatin-5FU-based CRT with cisplatin 5FU-based CRT in patients with inoperable but localised oesophageal cancer has demonstrated no significant difference in survival or toxicity but the ease of administration of oxaliplatin over cisplatin makes it a more attractive option [16].…”

Phase I study of concurrent selective lymph node late-course accelerated hyperfractionated radiotherapy and S-1 plus cisplatin for locally advanced oesophageal squamous cell carcinoma

“…The toxicities were slighter and response rates were encouraging in this trial in comparison with other previous studies. [3][4][5][6]8,9,[31][32][33] Given the overall size of this study, the results of the follow-up have been reviewed cautiously. However, the high response rate, milder toxicities and OS time when administering S-1, CDDP and LCAF RT were encouraging and support further Phase II or Phase III trial testing in locally advanced ESCC.…”