Neoadjuvant Cisplatin–Fluorouracil Best For Operable Oesophageal Adenocarcinoma

Neoadjuvant epirubicin, cisplatin and capecitabine in patients with surgically resectable oesophageal adenocarcinoma does not improve overall survival over that achieved by cisplatin plus fluorouracil

medwireNews: Four cycles of neoadjuvant epirubicin, cisplatin and capecitabine (ECX) does not offer an overall survival (OS) benefit over two cycles of cisplatin plus fluorouracil (CF) for patients with operable oesophageal adenocarcinoma, phase III results indicate.

Median OS was 26.1 months for the 446 patients with stage cT1N1, cT2N1, cT3N0/N1 or cT4N0/N1 disease who were given the ECX regimen before undergoing two-phase oesophagectomy with abdomen and thorax lymphadenectomy.

This did not significantly differ from the 23.4 months achieved by the 451 patients given CF, prompting the investigators to recommend that “two cycles of CF should remain the standard choice of neoadjuvant chemotherapy regimen” in this population.

Disease-free survival at the 6-month landmark analysis was a median of 14.4 months with ECX versus 11.6 months with CF, giving a nonsignificant difference between the two groups, although exploratory analysis of progression-free survival suggested that ECX was superior for this outcome, at a median of 21.4 versus 18.4 months and a significant hazard ratio of 0.84.

David Cunningham, from The Royal Marsden NHS Foundation Trust in London, UK, and co-workers found that year of recruitment had a significant impact on outcome, with patients entering the study during 2005–2011 deriving significantly better OS with CF than patients recruited from 1992–1998, at 2.0 versus 1.4 years.

This finding may be linked to changes in referral patterns, uptake of endoscopic ultrasound and introduction of multidisciplinary teams, they suggest.

The introduction of positron emission tomography (PET) scanning may also have played a role in the lack of survival difference noted in the study, the authors say, noting that ECX was associated with a survival benefit in the early years of the study, when PET scans were rarely used.

“ECX might be more effective in treating small-volume, disseminated disease that was often missed before the routine use of PET scans”, the authors hypothesise in The Lancet Oncology. “Patients with this type of disease are now usually identified and would have been ineligible for participation in the study.”

The team observes that “[c]hemotherapy toxicity and serious adverse events were reported more often with ECX—as can be expected from four cycles of a triplet regimen compared with two cycles of a doublet regimen.”

In particular, ECX-treated patients were significantly more likely to have grade 3 or 4 diarrhoea (8 vs 1%) and neutropenia (23 vs 17%) than their CF-treated counterparts, although ECX was associated with a significantly reduced rate of grade 3 or 4 stomatitis (2 vs 6%).

The higher rate of any grade 3–5 toxicity (49 vs 31%) and serious adverse events (24 vs 16%) with ECX than CF resulted in significantly fewer ECX-treated patients completing their chemotherapy regimen (81 vs 96%).

ECX was also associated with a lower rate of surgery than CF (87 vs 91%), although the researchers note that postoperative complications and mortality did not differ between the groups.

Reference

Alderson D, Cunningham D, Nankivell M, et al. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial. Lancet Oncol; Advance online publication 4 August 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30447-3

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