Abstract
PurposeNeoadjuvant chemoradiation (nCRT) is the treatment of choice for patients with locally advanced squamous cell carcinoma of the esophagus (SCC). Today radiation oncologists can choose between two different therapy regimes including chemoradiation with cisplatin and 5-fluoruracil (CDDP/5FU) and chemoradiation analogue to the CROSS-regime with carboplatin and paclitaxel (Carb/TAX). However, there is a lack of studies comparing these regimes, especially for the subgroup of patients with SCC. In this study, we want to compare nCRT with CDDP/5FU and nCRT with Carb/TAX for patients with locally advanced SCC.Patients and methodsWe retrospectively compared 20 patients who were scheduled for nCRT with a total radiation dose of 41.4 Gy (daily dose of 1.8 Gy) and weekly chemotherapy with carboplatin (Area under the curve 2) and Paclitaxel (50 mg per square meter of body-surface area) according to the CROSS-regime to 31 patients who were scheduled for nCRT with a total radiation dose of 45 Gy (daily dose of 1.8 Gy) and simultaneous chemotherapy with cisplatin (20 mg/m2/d) and 5-fluoruracil (500 mg/m2/d) on day 1–5 and day 29–33. For the per-protocol (PP) analysis, per protocol treatment was defined as either complete radiation with 41.4 Gy, at least three complete cycles of Carb/TAX and subsequent surgery or complete radiation with 45 Gy, at least one complete cycle of CDDP/5FU and subsequent surgery.ResultsFifty-one patients (31 patients treated with CDDP/5FU and 20 patients treated with Carb/TAX) were evaluated for the intention-to-treat (ITT) analysis and 44 patients (26 patients treated with CDDP/5FU and 18 patients treated with Carb/TAX) were evaluated for the PP analysis. No significant differences were seen for baseline and tumor characteristics like age, sex, TNM-stage, grading and tumor extension between patients treated with Carb/TAX and patients treated with CDDP/5FU. The most common tumor regression grade after nCRT was grade I as classified by Becker et al., which was observed in 84 and 79% of patients. No significant differences in tumor regression grades were seen between both regimes. Postoperative insufficiency of the anastomosis was seen in 6 patients (33%) who were treated with Carb/TAX and 4 patients (15%) who were treated with CDDP/5FU (p = 0.273). Patients treated with CDDP/5FU developed significantly more cumulative hematologic III° (CTCAE) toxicities (58% vs 20%; p = 0.010) than patients treated with Carb/TAX. In contrast to that, there was no significant difference for overall survival (OS) and freedom from relapse (FFR) between treatment groups.ConclusionIn this retrospective analysis, no significant difference was seen for OS and FFR between nCRT with CDDP/5FU and nCRT with Carb/TAX. However, the application of CDDP/5FU was associated with significantly more hematologic III°- toxicities compared to Carb/TAX. Future prospective trials should investigate if these results are reproducible in randomized patient cohorts.
Highlights
With 400.000 estimated deaths and 456.000 new cases in 2012 esophageal cancer (EC) is the sixth most common cause of cancer death and the eighth most common cancer in the world [1].In 2008, Tepper et al [2] demonstrated the superiority of neoadjuvant chemoradiation with cisplatin and 5-fluoruracil (CDDP/5FU) combined with subsequent surgery compared to surgery alone
Fifty-one patients (31 patients treated with CDDP/5FU and 20 patients treated with Carb/Carboplatin and Paclitaxel (TAX)) were evaluated for the intention-to-treat (ITT) analysis and 44 patients (26 patients treated with CDDP/5FU and 18 patients treated with Carb/TAX) were evaluated for the PP analysis
No significant differences were seen for baseline and tumor characteristics like age, sex, TNM-stage, grading and tumor extension between patients treated with Carb/TAX and patients treated with CDDP/5FU
Summary
In 2008, Tepper et al [2] demonstrated the superiority of neoadjuvant chemoradiation (nCRT) with cisplatin and 5-fluoruracil (CDDP/5FU) combined with subsequent surgery compared to surgery alone. Multimodal treatment was associated with a significant increase in terms of overall survival and progression-free survival and nCRT with CDDP/5FU and subsequent resection became the treatment of choice for patients with locally advanced squamous cell carcinoma of the esophagus (SCC) suitable for surgery. In the more recent CROSS-study, van Hagen et al [3] compared nCRT with carboplatin and paclitaxel (Carb/TAX) and subsequent surgery to surgery alone in patients with locally advanced EC. Comparable to the results of Tepper et al patients treated with nCRT with Carb/TAX had a significantly improved overall survival and disease-free survival compared to patients treated with surgery alone. Thereby, the effect of nCRT was much higher for patients with SCC than for patients with AC
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