Capecitabine and cisplatin chemotherapy (XP) alone or sequentially combined chemoradiotherapy containing XP regimen in patients with three different settings of stage IV esophageal cancer

Background: The 1997 staging system for esophageal carcinoma subdivided distant metastatic disease (M1) into nonregional lymph node metastases (M1a) and other metastases (M1b). To determine the relevance of this classification system, we investigated the efficacy and toxicity of capecitabine/cisplatin (XP) chemotherapy alone or in combination with radiotherapy. Methods: We identified 74 patients with M1 disease treated at Asan Medical Center from January 2003 to December 2005. Of these patients, 19 (25.7%) were classified as M1a, 29 (39.2%) as M1b (nonvisceral lymph node metastases), and 26 (35.1%) as M1b (visceral metastases). All patients were treated with first two cycles of XP induction chemotherapy, consisting of capecitabine 1000 mg/m² twice daily on days 1-14, and i.v. cisplatin 60 mg/m² on day 1, every 3 weeks. Patients classified as M1a and M1b (nonvisceral lymph node metastases) were treated with 54 Gy of radiotherapy, concurrently with weekly capecitabine 800 mg/m² twice daily on days 1-5 and i.v. cisplatin 30 mg/m² on day 1 during radiation. Patients classified as M1b (visceral metastases) were treated with chemotherapy only until disease progression or intolerance to chemotherapy. Results: In response to the first two cycles of chemotherapy, 3/18 (16.7%) M1a nonregional lymph node (LN), 4/27 (14.8%) M1b nonvisceral LN metastases and 5/25 (20%) M1b visceral metastases patients attained partial responses. After definitive chemoradiation in the setting of M1a, M1b nonvisceral LN metastases and maximum cycles of chemotherapy in the M1b visceral metastases setting, the response rates were 77.8, 62.9 and 36.0% respectively. With median follow-up of 12.5 months (range 0.5%22.8), 50 of 74 patients (67.5%) died. The median time to progression (TTP) was 7.8 months (95% CI, 6.0-9.5 months) and the median overall survival (OS) was 12.0 months (95% CI, 9.0-15.0 months). Median TTP in the M1a, M1b nonvisceral LN metastases and M1b visceral metastases were 10.3, 6.5 and 5.9 months, respectively (P = 0.087), whereas median OS in these groups was 13.8, 13.8, and 8.2 months, respectively (P = 0.134). Median TTP was 8.4 months (95% CI, 5.5-11.3 months) in the 48 patients with M1a and M1b nonvisceral LN metastases and 5.9 months (95% CI, 2.7-9.0 months) in the 26 patients with M1b visceral metastases (P = 0.03), and median OS in these two groups was 13.8 months (95% CI, 10.4-17.3 months) and 8.2 months (95% CI, 5.7-10.7 months), respectively (P = 0.04). Conclusion: The similar OS in patients with M1a and M1b nonvisceral LN metastases suggests that concurrent chemoradiotherapy might contribute in the latter. Our findings indicate that sequentially combined chemoradiotherapy containing XP regimen was active and well tolerated as first-line treatment for M1a as well as M1b esophageal cancer.