Chemotherapy is associated with a survival benefit in advanced gastric cancer. Several options exist, including EOX. The regimen docetaxel, cisplatin and 5-fluorouracil (DCF) is toxic and modifications have been developed. In our institution CTX was a standard treatment from 2004 to 2012 when it was replaced by EOX. Afterwards, a randomised trial with CTX was conducted.
SEED was a prospective, single-center, phase 2 trial in unresectable HER2-negative esophagogastric adenocarcinoma. Patients were randomised to either docetaxel 60 mg/m2, carboplatin AUC5 and capecitabine 1000 mg/m2 bd for 14 days q4w (CTX) or epirubicin 50 mg/m2, oxaliplatin 130 mg/m2 and capecitabine 625 mg/m2 bd for 21 days q3w (EOX). Treatment continued until progression, intolerance or a maximum of 9 cycles. The primary endpoint was 1-year-survival for patients treated with CTX. The trial sought to accept (lower boundary 55%) or reject (higher boundary 40%) CTX for further study without making direct comparisons to EOX. Secondary endpoints included OS, PFS and grade 3/4 toxicities.
From 2014 to 2019 a total of 98 patients were randomised (49 in each arm). The median age was 63 (36 - 79). Male/female: 79/19; ECOG PS (0/1): 46/52; oesophageal/GEJ/gastric: 29/44/25; metastatic/non-metastatic: 96/2. As of 26 April 2019, 85 patients had died. The estimated 1-year survival was 32% (95% CI 19 - 46) for CTX and 39% (95% CI 25 - 52) for EOX. The median PFS and OS was 6.2 months (95% CI 5.2 - 7.2) and 9.2 months (95% CI 7.2 - 11.2), respectively, for CTX, and 5.2 months (95% CI 3.5 - 7.0) and 10.2 months (95% CI 7.9 - 12.4), respectively, for EOX. Grade 3/4 related toxicities in > 5% were neutropenia (78%), febrile neutropenia (25%), diarrhoea (8%) and fatigue (6%) for CTX, and neutropenia (49%), febrile neutropenia (10%), peripheral neuropathy (8%) and nausea (8%) for EOX. There were no treatment-related deaths.
CTX resulted in a 1-year-survival rate of 32% and so is rejected for further study. Also, CTX had a high rate of febrile neutropenia. CTX is not recommended for patients with esophagogastric cancer, except selected patients intolerant of other standard therapies, and then only with G-CSF support.
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