S-1 Based Simultaneous Integrated Boost Radiotherapy Followed By Consolidation Chemotherapy With S-1 For Esophageal Squamous Cell Carcinoma In The Elderly - A Multicenter Phase Ii Study (3jecrog P-01)

This study aimed to assess the toxicity profile and efficiency of S1 based simultaneous integrated boost radiotherapy (SIB-RT) followed by consolidated chemotherapy with S1 in elderly pts with esophageal cancer (EC) and to evaluate the feasibility and usefulness of comprehensive geriatric assessment (CGA). We enrolled pts if they met the following criteria with stratifications of medical center and clinical TNM stage: (1) ≥ 70 years, (2) histopathologically proved squamous cell carcinoma of EC, (3) clinical stage II-III, or IV consisting of metastatic lymph nodes in the supraclavicular/abdominal para-aortic area according to AJCC 6th, (4) Charlson score ≤ 3. SIB-RT consisted two dose levels (59.92 and 50.4 Gy in 28 fractions) with concurrent S-1 80, 100, 120 mg/d based on body surface area, 5 days/week. S-1 was repeated up to four cycles (the same daily dosage as chemoradiotherapy (CRT), days 1-14, every 3 weeks) 4-8 weeks after CRT. The primary endpoint was overall responding rate (ORR) determined within three months after CRT. All pts completed CGA before CRT including functional status, comorbidity, cognitive function, psychological state, social support, and nutritional status. Among these questionnaires, QOL and dysphagia were evaluated before and after CRT. This trial was registered with ClinicalTrials.gov, number NCT 02979691. Between September 2016 and March 2017, 46 pts (median age, 75 years; stage II vs III vs IV, 21 vs 19 vs 6, 46% vs 41% vs 13%) were enrolled from eight medical centers. The ORR was seen in 36 (78.3%) pts. Grade 3 toxicities were: esophagitis (5, 11%), nausea (4, 9%) and anorexia (3, 7%). No Grade 4-5 toxicity occurred. Consolidation monotherapy with S-1 was continued for 2 cycles in 37 pts (80%), 3 cycles in 32 pts (70%), and 4 cycles in 30 pts (65%). The reasons for withdrawal of S-1 monotherapy included refusal of the patient (5 pts) and poor recovery from CRT (1 pts). With a median follow-up time of 22.4 months, the median overall survival was 22.1 months. The 1- and 2- year overall survival, progression-free survival, locoregional-recurrence free survival and distant-metastasis free survival were 80.4% and 48.9%, 71.3% and 52.4%, 79.8% and 67.0%, 86.1% and 80.7%, respectively. The scores of QOL (P=0.119) and dysphagia (P=0.106) showed no significant difference after CRT compared to baseline. However, 70% of the pts were found to be with malnutrition, 40% with poor activities of daily living, 36% with cognitive impairment, and 27% with moderate to severe depression at diagnosis before CRT. S-1 with concurrent SIB-RT followed by four cycles of S-1 monotherapy was feasible and tolerable for selected elderly pts with EC. It was worth noticing that CGA could uncover numerous health problems in the elderly before treatment and may allow appropriate support of care provided for these pts. A multicenter randomized phase III study comparing S-1 based SIB-RT followed by S-1 monotherapy with SIB-RT alone for EC in the elderly is ongoing.