Comparison of efficacy and safety of first-line palliative chemotherapy with EOX and mDCF regimens in patients with locally advanced inoperable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma: a randomized phase 3 trial.
The aim of the study was to compare efficacy and safety of first-line palliative chemotherapy with (EOX) epirubicin/oxaliplatin/capecitabine and (mDCF) docetaxel/cisplatin/5FU/leucovorin regimens for untreated advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma. Fifty-six patients were randomly assigned to mDCF (docetaxel 40 mg/m(2) day 1, leucovorin 400 mg/m(2) day 1, 5FU 400 mg/m(2) bolus day 1, 5FU 1000 mg/m(2)/d days 1 and 2, cisplatin 40 mg/m(2) day 3) or EOX (epirubicin 50 mg/m(2) day 1, oxaliplatin 130 mg/m(2) day 1, capecitabine 1250 mg/m(2)/d days 1-21). The primary endpoint was overall survival. The median overall survival was 9.5 months with EOX and 11.9 months with mDCF (p = 0.135), while median progression-free survival was 6.4 and 6.8 months, respectively (p = 0.440). Two-year survival rate was 22.2 % with mDCF compared to 5.2 % with EOX. Patients in the EOX arm had more frequent reductions in chemotherapy doses (34.5 vs. 3.7 %; p = 0.010) and delays in subsequent chemotherapy cycles (82.8 vs. 63.0 %; p = 0.171). There was no statistically significant difference in the rates of grade 3-4 adverse events (EOX 79.3 vs. mDCF 61.5 %; p = 0.234). As compared with the mDCF, the EOX regimen was associated with more frequent nausea (34.5 vs. 15.4 %), thromboembolic events (13.8 vs. 7.7 %), abdominal pain (13.8 vs. 7.7 %) and grades 3-4 neutropenia (72.4 vs. 50.0 %), but lower incidences of anemia (44.8 vs. 61.5 %), mucositis (6.9 vs. 15.4 %) and peripheral neuropathy (6.9 vs. 15.4 %). In conclusion, the mDCF regimen was associated with a statistically nonsignificant 2.4-month longer median overall survival without an increase in toxicity. This trial is registered at ClinicalTrials.gov, number NCT02445209.
Department of Oncology, Jagiellonian University Medical College, Ul.Sniadeckich 10, 31-531, Kraków, Poland. sebaochenduszko@gmail.com.
Sebastian
http://orcid.org/0000-0002-0126-8418
S
Ochenduszko
Department of Oncology, Jagiellonian University Medical College, Ul.Sniadeckich 10, 31-531, Kraków, Poland.
Miroslawa
M
Puskulluoglu
Department of Clinical Oncology, University Hospital in Krakow, Kraków, Poland.
Kamil
K
Konopka
Department of Statistics, Cracow University of Economics, Kraków, Poland.
Kamil
K
Fijorek
Department of Pathology, Jagiellonian University Medical College, Kraków, Poland.
Katarzyna
K
Urbanczyk
2nd Department of General Surgery, Jagiellonian University Medical College, Kraków, Poland.
Andrzej
A
Budzynski
2nd Department of General Surgery, Jagiellonian University Medical College, Kraków, Poland.
Maciej
M
Matlok
Department of Pathology, Jagiellonian University Medical College, Kraków, Poland.
Agata
A
Lazar
Department of Pathology, Jagiellonian University Medical College, Kraków, Poland.
Anna
A
Sinczak-Kuta
2nd Department of General Surgery, Jagiellonian University Medical College, Kraków, Poland.
Michal
M
Pedziwiatr
Department of Oncology, Jagiellonian University Medical College, Ul.Sniadeckich 10, 31-531, Kraków, Poland.
Krzysztof
K
Krzemieniecki
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D004943:Esophagogastric Junction; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010166:Palliative Care; D018719:Erb-b2 Receptor Tyrosine Kinases; D013274:Stomach Neoplasms / Q000188:drug therapy*
D000069287:Capecitabine; D002945:Cisplatin; D015251:Epirubicin; D005472:Fluorouracil; D002955:Leucovorin; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D018719:Erb-b2 Receptor Tyrosine Kinases
EOX; Gastric cancer; Palliative chemotherapy; Safety; Toxicity; mDCF