Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF

Sumpter, Katherine; Harper‐Wynne, Catherine; Cunningham, David; S, Rao; Tebbutt, Niall C.; Norman, A.; Ward, Carol; Iveson, Tim; Nicolson, Marianne; Hickish, Tamas; Hill, Mark; Oates, J.

doi:10.1038/sj.bjc.6602572

Cited by 141 publications

(90 citation statements)

References 27 publications

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“…Adverse events were assessed at every treatment visit and were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0. Dose modifications were instituted as previously described (Sumpter et al, 2005). Cisplatin was discontinued in the presence of clinically significant ototoxicity or peripheral neuropathy and substituted by carboplatin at the discretion of the investigator.…”

Section: Treatmentmentioning

confidence: 99%

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

et al. 2009

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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.

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Section: Treatmentmentioning

confidence: 99%

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

et al. 2009

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“…Phase II studies of capecitabine given as a single agent or in combination with a variety of other active agents have been carried out and produced promising response rates (Hong et al, 2004;Lorenzen et al, 2005). Preliminary data from the randomised 'REAL 2' trial in this disease show that capecitabine can be substituted for infusional FU as part of the ECF regimen without loss of efficacy (Sumpter et al, 2005). Preclinical data suggest that capecitabine and irinotecan may act synergistically (Hapke et al, 2001).…”

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confidence: 99%

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma

et al. 2006

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We investigated 2-weekly intravenous irinotecan combined with oral capecitabine in patients with advanced gastroesophageal adenocarcinoma. In phase I, doses were escalated in chemotherapy naïve or pretreated patients to establish maximum tolerated doses (MTD). In phase II, patients were treated at MTD as first-line therapy with the primary end point of RECIST response. Dose levels in phase I were as follows: Level 1: irinotecan 150 mg m À2 on day 1; capecitabine 850 mg m À2 12-hourly on days 1 -9. Level 2: as level 1 but capecitabine 1000 mg m À2 . Level 3: as level 2 but irinotecan 180 mg m À2 . Level 4: as level 3 but capecitabine 1250 mg m À2 . In phase I, 21 patients were entered. Maximum tolerated dose was level 3. Dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis. In phase II, 31 patients were entered at level 3. During the first six cycles, 13 of these patients underwent dose reduction and three patients stopped treatment for toxicity. A further six patients stopped for progressive disease. The commonest grade 3 -4 toxicities were lethargy (20%), diarrhoea (17%), nausea (10%) and anorexia (10%). There were no treatment-related deaths. The response rate was 32% (95% CI 16 -52%). Median overall survival was 10 months. This regimen is active in gastroesophageal adenocarcinoma. However, using the MTD defined in phase I, fewer than 50% patients tolerated six cycles without modification in phase II; therefore, modification of these doses is recommended for further study.

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“…43,44 The regimen's manageability and patient compliance may be improved further by substituting FU with oral fluoropyrimidines, which can overcome catheter-related risks without compromising treatment activity. 45,46 Despite the observational nature of this study, the PEFG regimen appears to have interesting activity against BTA with manageable toxicity, which may be improved further with the modified schedule that is used in pancreatic cancer. [43][44][45] In the absence of evidence-based treatment guidelines, this regimen may represent a therapeutic option for the management of patients with biliary tract cancer.…”

Section: Discussionmentioning

confidence: 92%

The cisplatin, epirubicin, 5‐fluorouracil, gemcitabine (PEFG) regimen in advanced biliary tract adenocarcinoma

Cereda

Passoni

Reni

et al. 2010

Cancer

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BACKGROUND: Biliary tract adenocarcinoma (BTA) is an uncommon tumor with a poor prognosis and no standard, systemic chemotherapy. The combined cisplatin, epirubicin, 5-fluorouracil, and gemcitabine (PEFG) regimen is an effective, upfront treatment for advanced pancreatic cancer. In this study, the authors assessed the activity and safety of this combination regimen in patients with advanced BTA. METHODS: PEFG (cisplatin 40 mg/m 2 and epirubicin 40 mg/m 2 on Day 1; gemcitabine 600 mg/m 2 on Days 1 and 8; and 5-fluorouracil [FU] 200 mg/m 2 daily as a continuous infusion) was administered to chemotherapy-naive patients who had a cytologic or histologic diagnosis of locally advanced or metastatic BTA, aged 75 years, and a performance status (PS) >60 either until they had evidence progressive disease or for a maximum of 6 months. Tumor size was assessed every 2 months during treatment. RESULTS: Between May 1999 and December 2005, 37 patients (62% metastatic) who had a median age of 62 years and a median PS of 90 received the PEFG regimen at the authors' institution. Primary tumor sites were the intrahepatic bile duct in 10 patients (27%), the extrahepatic bile duct in 8 patients (22%), the gallbladder in 12 patients (32%), and the ampulla of Vater in 7 patients (19%). A partial response was observed in 16 patients (43%), and stable disease was observed in 12 patients (32%). The median overall survival (OS) was 12.1 months, and the 1-year OS rate was 52%. The median progression-free survival (PFS) was 7.9 months, and the 6-month PFS rate was 67%. The main grade 3/4 toxicity was neutropenia in 18% of cycles followed by thrombocytopenia in 9% of cycles, nausea/vomiting in 5% of cycles, and febrile neutropenia, fatigue, anemia, and stomatitis in 2% of cycles. CONCLUSIONS: The current results demonstrated that PEFG was an active regimen with a manageable toxicity profile for patients with advanced BTA.

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Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF

Cited by 141 publications

References 27 publications

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

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

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma

The cisplatin, epirubicin, 5‐fluorouracil, gemcitabine (PEFG) regimen in advanced biliary tract adenocarcinoma

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