Abstract 402P
Background
The main purpose of this study is to evaluate the long-term outcomes of phase I study aiming at evaluating the maximum tolerated dose (MTD) in proton beam therapy (PBT) with concurrent full-dose chemotherapy (5FU and CDDP) for patients with esophageal squamous cell carcinoma (ESCC).
Methods
The protocol was approved by the Institutional Review Board (2014-123). A total of 12 patient with ESCC were enrolled in a phase 1 trial. 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/m2 and CDDP 75 mg/m2. Dose-limiting toxicity (DLT) was defined as the following toxicities occurring within 90 days after PBT: 1) Grade (G) ≥3 non-hematological toxicities, 2) G ≥2 esophageal fistula, 3) G ≥3 pneumonitis according to NCI CTCAE v4.03) more than 22 days’ interruption of PBT. Following the trial, long-term outcomes such as overall survival (OS) and progression free survival (PFS) were assessed.
Results
The planned treatment was completed in all patients. No ≥G3 toxicities or treatment interruption was observed within 90 days after PBT at any DL. The median follow-up duration was 87 months for surviving patients. 5-year and 7-year OS/PFS were 75% / 50% and 75% / 50%, respectively. Four patients had died of disease progression and the remaining 8 are alive disease-free. Among the 12 patients, 6 recurred: 3 in DL1 and 3 in DL2. Notably, a DL1 patient developed Grade 3 gastric bleeding at 9 months after PBT initiation and Grade 2 pericardial effusion at 42 months. Another DL1 patient developed Grade 2 esophageal stenosis at 18 months from PBT initiation.
Conclusions
The long-term analysis exhibited the potential of escalated dose PBT with full-dose concurrent chemotherapy as an effective treatment for ESCC, exhibiting favorable toxicity profiles over an extended period. These results encourage further validation in larger, multi-institutional trials to optimize treatment strategies for ESCC.
Clinical trial identification
jRCTs032180029, 20/10/2021.
Legal entity responsible for the study
Hidehiro Hojo.
Funding
Has not received any funding.
Disclosure
T. Kojima: Financial Interests, Personal, Invited Speaker: MSD, Bristol Myers Squibb, Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Kyowa Kirin, Taiho Pharmaceutical; Financial Interests, Institutional, Invited Speaker: AstraZeneca, BeiGene, MSD, Amgen, Chugai Pharmaceutical, Taiho Pharmaceutical, Shionogi Pharma, Amgen Astellas BioPharma. M. Nakamura: Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Institutional, Funding: Illumina. All other authors have declared no conflicts of interest.