A phase II trial of preoperative chemotherapy with epirubicin, cisplatin and capecitabine for patients with localised gastro-oesophageal junctional adenocarcinoma

Abstract

Preoperative cisplatin/fluorouracil is used for the treatment of localised oesophageal carcinoma. This phase II study aimed to assess the efficacy and safety of administering preoperative epirubicin/cisplatin/capecitabine (ECX). Patients with stage II or III oesophageal/ gastro-oesophageal junctional adenocarcinoma from one institution received 4 cycles of ECX (epirubicin 50 mg m À2 day 1, cisplatin 60 mg m À2 day 1, capecitabine 625 mg m À2 b.i.d. daily) followed by surgery. The primary end point was the pathological complete response (pCR) rate based on a Simon two-stage design. Secondary end points included overall and progression-free survival (OS/ PFS). Thirty-four patients were recruited: median age 60 years (range 41 -81), 91% male, 97% PS 0/1, 80% T3, 68% N1. Thirty-one patients completed four ECX cycles. Grade 3/4 toxicities X5% included neutropenia (62%), hand -foot syndrome (15%) and nausea/ vomiting (9%). Thirteen out of 28 (46%) evaluable patients responded to chemotherapy by EUS (X30% reduction in maximal tumour thickness). Twenty-six out of 34 (76%) patients underwent resection (R0 ¼ 73%, R1 ¼ 27%). Post-operatively, two patients died within 60 days of surgery. The pCR rate was 5.9% (95% CI 0 -14%) in the intent-to-treat population. According to the statistical design, this prompted early study termination. However, with a median follow-up of 34 months the median OS and 1-and 2-year survival rates were 17 months, 67 and 39% respectively. Median PFS was 13 months. Of the 14 relapsed patients, 10 presented with distant metastases. Preoperative ECX is feasible and well tolerated. Although associated with a low pCR rate, survival with ECX was comparable with published studies suggesting that pCR may not correlate with satisfactory outcome from preoperative chemotherapy for localised oesophageal adenocarcinoma.

Perioperative chemotherapy with docetaxel, cisplatin and capecitabine (DCX) in gastro-oesophageal adenocarcinoma: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

“…One patient died during preoperative chemotherapy due to a pulmonary embolism, and another died 6 weeks postoperatively without any relation to chemotherapy. This is comparable with other studies [23,28,29].…”

“…[23]. The pCR rate was 13.7% (N = 51, k = 7, 95% CI 6.5-26.0), which again compares well with a rate of 5.9% after four cycles of epirubicin, cisplatin and capecitabine [28], 0% in the MAGIC trial [2] and 3% in the Ychou et al study [3]. Table 4 summarizes the pCR rate for these and other trials.…”

“…It is postulated that a pCR rate predicts an extension of survival [29,34], although this has to be further evaluated. Our 1-year survival rate of 88.0% with the DCX regimen and the 91% reported by Homann et al [29] were higher than that in the Starling et al study (67%) [28], which used a taxane-free regimen.…”

Histopathological regression after taxane based neoadjuvant chemotherapy in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma

“…The pCR rate with the use of epirubicin based chemotherapy have ranged from 6-8% (15,16). The use of docetaxel based chemotherapy has increased the pCR rate upto 20% as seen in Neo-FLOT (14).…”

High Impact of Histopathological Remission for Prognosis after Perioperative Chemotherapy with ECF and ECF-Like Regimens for Gastric and Gastroesophageal Adenocarcinoma

“…In trials with homogeneous chemotherapy regimens, a retrospective analysis showed a 17.4% (8/46 patients) pCR rate after 5-FU, oxaliplatin and docetaxel (FLOT) in a group of R0-resected patients [16]. Prospective studies achieved a 13.7% (7/51 patients) pCR rate using docetaxel, cisplatin and capecitabine (DCX) [17], a 10.0% (4/41 patients) pCR rate using docetaxel, cisplatin and 5-FU (DCF) [18], a 5.9% (2/34 patients) pCR rate using epirubicin, cisplatin and capecitabin (ECX) [19], a 3.0% (3/109 patients) pCR rate using CF [5] or even a 0% (0/250 patients) pCR rate using epirubicin, cisplatin and fluorouracil (ECF) [2]. …”