A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer

Aristotelis Bamias (1, 2) , M. Karina (3) , P. Papakostas (4) , I. Kostopoulos (5) , M. Bobos (5) , G. Vourli (6) , E. Samantas (7) , Ch. Christodoulou (8) , G. Pentheroudakis (9) , D. Pectasides (10) , M. A. Dimopoulos (1) , G. Fountzilas (3)

1 Department of Clinical Therapeutics
2 Oncology Unit
3 Department of Medical Oncology, “Papageorgiou” Hospital
4 Department of Medical Oncology
5 Department of Pathology
6 Hellenic Cooperative Oncology Group Data Office, Section of Biostatistics
7 Third Department of Medical Oncology
8 Second Department of Medical Oncology
9 Department of Medical Oncology
10 Second Department of Internal Medicine, Propaedeutic, Oncology Section

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 ≥T3 and/or N+ were randomized to 6 cycles of docetaxel with cisplatin, both at 75 mg/m 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  = 0.016) and OS (63.2 vs. 18.8 months, Wald  = 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.

Mots clés: Adjuvant chemotherapy; Gastric cancer; Docetaxel; Radiotherapy; TMA; ERCC1; HER2; MAP-Tau

Aristotelis Bamias, M. Karina, P. Papakostas, I. Kostopoulos, M. Bobos, et al.. A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer. Cancer Chemotherapy and Pharmacology, 2010, 65 (6), pp.1009-1021. ⟨10.1007/s00280-010-1256-6⟩. ⟨hal-00562713⟩