Gastrointestinal Cancer

MO 03 - GI 1 - Esophagogastric Cancers

1034 - Phase I Dose-Escalation Trial of Proton Beam Therapy with Concurrent Full-Dose Chemotherapy for Patients with Cstage IB/II/III(non-T4) Esophageal Squamous Cell Carcinoma

Sunday, September 15
5:15 PM - 5:20 PM
Location: Room W178

Phase I Dose-Escalation Trial of Proton Beam Therapy with Concurrent Full-Dose Chemotherapy for Patients with Cstage IB/Ⅱ/Ⅲ(non-T4) Esophageal Squamous Cell Carcinoma
T. Akimoto1, T. Kojima2, H. Hojo1, M. Onozawa1, M. Okumura1, M. Nakamura1, A. Motegi1, K. Hotta1, H. Baba1, S. Zenda1, T. Fujita3, N. Nakamura1, and H. Daiko3; 1Division of Radiation Oncology and Particle Therapy, National Cancer Center Hospital East, Kashiwa, Japan, 2Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan, 3Department of Esophageal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan

Purpose/Objective(s): Chemoradiation therapy (CRT) with the standard radiation dose of 50.4 Gy or 60 Gy is one of the treatment options for patients with esophageal squamous cell carcinoma (ESCC). However, the clinical outcomes are still not satisfactory and treatment-related toxicities such as cardio-pulmonary toxicities remain a concern when considering increase of the treatment intensity of CRT. The primary objective of this study was to evaluate the maximum tolerated dose (MTD) in proton beam therapy (PBT) with concurrent full-dose chemotherapy (5FU and CDDP) for patients with ESCC, and to determine the recommended dose (RD). We hypothesized that dose-escalated PBT with concurrent chemotherapy for ESCC would have acceptable toxicity.

Materials/Methods: The protocol was approved by the Institutional Review Board (2014-123). The tested dose levels (DL) were: 2 GyE x 30 fr. (DL1) and 2 GyE x 33 fr. (DL2). Concurrent chemotherapy consisted of 5-FU 1000 mg/m2and CDDP 75 mg/m2, and two cycles were delivered during the PBT. Two cycles of adjuvant chemotherapy were indicated for patients who achieved complete response (CR) or good partial response (PR) to the PBT. Dose escalation of PBT followed a 6+6 rule-based design, with 12 patients required at the MTD. Dose-limiting toxicity (DLT) was defined as the following toxicities or events occurring within 90 days after PBT: 1) Grade (G) ≥3 non-hematological toxicities, excluding nausea, vomiting fatigue, esophagitis dermatitis, dysphagia, etc., 2) G ≥2 esophageal fistula, 3) G ≥3 pneumonitis according to NCI CTCAE v4.03, or 4) more than 22 days’ interruption of PBT.

Results: Twelve patients were enrolled (6 at DL1, 6 at DL2), and the median follow-up period was 35 months (range, 9 to 44 months). The planned treatment was completed in all patients, and 9 patients (6 at DL1, 3 at DL2) received 2 cycles of adjuvant chemotherapy. No ≥G3 toxicities or treatment interruption was observed at any DL. 3/6 in DL1, and 4/6 in DL2 experienced G2 esophagitis during the PBT. All acute G2 GI toxicities resolved within 90 days after completion of PBT. Nine (75%) achieved CR (6 at DL1, and 3 at DL2). Among the 3 patients with non-CR, 2 developed progressive disease and the third received esophageal mucosal resection for residual disease. At the time of the analysis, 2 patients had died of disease progression, one is alive with disease, and the remaining are alive disease-free.

Conclusion: Dose escalation of PBT with concurrent full-dose chemotherapy (5FU and CDDP) up to 2 GyE x 33 fr. for patients with ESCC was completed without any DLT, indicating that PBT at a total dose of 66 GyE with concurrent full-dose chemotherapy is feasible. A multi-institutional study using the RD determined in this study is warranted to clarify the efficacy of PBT with concurrent chemotherapy for patients with ESCC.

Author Disclosure: T. Akimoto: None. T. Kojima: None. H. Hojo: None. M. Nakamura: None. K. Hotta: None.

Tetsuo Akimoto, MD, PhD

National Cancer Center Hospital East

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National Cancer Center Hospital East

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1034 - Phase I Dose-Escalation Trial of Proton Beam Therapy with Concurrent Full-Dose Chemotherapy for Patients with Cstage IB/II/III(non-T4) Esophageal Squamous Cell Carcinoma



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