A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer.
The optimal adjuvant treatment for gastric cancer remains controversial. We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen, in patients with high-risk gastric cancer, with that of the same chemotherapy plus radiation therapy (RT). In addition, we evaluated the prognostic and/or predictive value of a panel of molecular markers. Patients with histologically proven, radically resected gastric cancer, stage > or =T3 and/or N+ were randomized to 6 cycles of docetaxel with cisplatin, both at 75 mg/m2 every 3 weeks (arm A) or the same treatment with RT (arm B; 45 Gy). Due to excessive nausea and vomiting, cisplatin was substituted by carboplatin at AUC (area under the curve) of 5 after the first 45 patients (22 group A, 23 group B). The prognostic value of EGFR, ERCC1, HER2, MET/HGFR, MAP-Tau, and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays (TMAs). A total of 147 patients were randomized. After a median follow-up of 53.7 months, no differences in overall (OS) and disease-free survival (DFS) were found between the two arms. The most common grade 3/4 toxicities for arms A and B (excluding alopecia) were non-febrile neutropenia (11 and 17%, respectively), febrile neutropenia (9 and 7%) and diarrhea (7 and 4%, respectively). Patients with ERCC1 positive tumors had significantly longer median DFS (33.1 vs. 11.8 months, Wald P = 0.016) and OS (63.2 vs. 18.8 months, Wald P = 0.046). Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk, radically resected gastric cancer. However, the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded.
Bamias
Aristotelis
A
Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece. abamias@med.uoa.gr
Karina
M
M
Papakostas
P
P
Kostopoulos
I
I
Bobos
M
M
Vourli
G
G
Samantas
E
E
Christodoulou
Ch
Ch
Pentheroudakis
G
G
Pectasides
D
D
Dimopoulos
M A
MA
Fountzilas
G
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000139:chemically induced; D000077143:Docetaxel; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D046888:Tissue Array Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D016190:Carboplatin; D002945:Cisplatin; D000077143:Docetaxel; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids