Phase I study of concurrent selective lymph node late-course accelerated hyperfractionated radiotherapy and S-1 plus...

This Phase I study aimed to assess the safety and efficacy of concurrent selective lymph node (SLN) late-course accelerated hyperfractionated (LCAF) intensity-modulated radiotherapy (IMRT) and S-1 plus cisplatin (CDDP) for the locally advanced oesophageal squamous-cell carcinoma (ESCC).

The total dose of SLN LCAF IMRT was 59.6 Gy/34 fractions in 5.4 weeks. The concurrent chemotherapy (CCRT) was administered as follows: CDDP 25 mg m(-2) on Days 1-3 and Days 22-24; S-1 was applied in a de-escalating dosage with a decrement of 10 mg m(-2) per day, from its full dose level of 80 mg m(-2), orally twice daily on Days 1-14 and Days 22-35. We inferred the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs) and recommended dose, according to adverse reaction during CCRT.

Totally, 15 patients with ESCC with T2-4N0-1M0-1a were enrolled in Dose Level 1 (80 mg m(-2)). In the initial five patients, two patients developed DLTs. As MTD was not reached, five additional patients were treated with the same dose level, and DLTs occurred in only one patient. Similar results were found in the last five patients. After CCRT, the objective response rates were 100% for primary tumours and 86.2% for metastatic lymph nodes, respectively. Totally, the observed Grade 3 toxicities during CCRT were leukopenia (20%), neutropenia (20%) and dermatitis (13.3%), and no Grade 4 toxicity occurred. The Kaplan-Meier-estimated overall and progression survival rates were 86.7% and 66.7% (1 year), 73.3% and 60% (2 years) and 73.3% and 60% (3 years).

The concurrent SLN LCAF IMRT and chemotherapy with S-1 and CDDP was well tolerated and showed promising efficacy. The dose of S-1 in this regimen was recommended with 80 mg m(-2) orally twice daily on Days 1-14 and Days 22-35.

CCRT with S-1 plus CDDP exhibited encouraging results with milder toxicities, high objective response rates and ideal overall survival time.