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

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Abstract

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/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.

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Acknowledgments

The authors wish to thank Ms. Evita Fragou for monitoring the study, Ms. Maria Moschoni for coordinating the data management, Ms. Thalia Spinari for coordinating tumor tissue collection (all at the HeCOG Data Office, Athens), and Sophia Chrisafi Ph.D. for excellent technical assistance. Supported in part by a HeCOG Research Grant: RD/2

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No author declared any conflict of interest.

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Authors and Affiliations

  1. Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece

    Aristotelis Bamias & M. A. Dimopoulos

  2. Department of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

    M. Karina & G. Fountzilas

  3. Department of Medical Oncology, “Hippokration” Hospital, Athens, Greece

    P. Papakostas

  4. Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece

    I. Kostopoulos & M. Bobos

  5. Hellenic Cooperative Oncology Group Data Office, Section of Biostatistics, Athens, Greece

    G. Vourli

  6. Third Department of Medical Oncology, “Agii Anargiri” Cancer Hospital, Athens, Greece

    E. Samantas

  7. Second Department of Medical Oncology, “Metropolitan” Hospital, Piraeus, Greece

    Ch. Christodoulou

  8. Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece

    G. Pentheroudakis

  9. Second Department of Internal Medicine, Propaedeutic, Oncology Section, “Attikon” University Hospital, Athens, Greece

    D. Pectasides

  10. Oncology Unit, Alexandra Hospital, 80 Vas. Sofias Ave., 115 28, Athens, Greece

    Aristotelis Bamias

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  1. Aristotelis Bamias
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Bamias, A., Karina, M., Papakostas, P. et al. A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer. Cancer Chemother Pharmacol 65, 1009–1021 (2010). https://doi.org/10.1007/s00280-010-1256-6

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