KEY TAKEAWAYS
- The study investigated the safety and efficacy of combining PTX with radiotherapy as a standard treatment for older patients with locally advanced ESCC.
- The primary endpoint was to determine the DLT.
- Researchers noticed that a weekly dose of 50 mg/m² of PTX with concomitant radiation was well-tolerated; further investigation is ongoing.
In older patients, esophageal squamous cell carcinoma (ESCC) is difficult to treat using standard therapies, including surgery and cisplatin-based chemoradiotherapy. Paclitaxel (PTX) has radiosensitizing activity.
Kenro Hirata and the team conducted a phase I trial of PTX combined with radiotherapy to establish a standard therapy for older patients with locally advanced ESCC.
They performed an inclusive analysis of patients enrolled at 6 centers from April 2016 to September 2019. The participants, aged ≥70 years, had locally advanced ESCC and were either intolerant to surgery or unwilling to undergo it. They received a fixed 60-Gy radiation dose administered in 30 fractions, with PTX dosing starting at 30 mg/m² weekly for 6 weeks.
Depending on the number of dose-limiting toxicities (DLTs), the PTX dose was adjusted by 10 mg/m² or changed to a biweekly schedule. A geriatric assessment was conducted before treatment using the Geriatric-8 screening tool. The primary endpoint of the study was DLT.
About 24 patients were enrolled (6 per group). DLTs were observed in 1 patient with grade 4 hypokalemia, 1 with grade 3 aspiration, 2 with grade 3 radiodermatitis and grade 3 esophageal hemorrhage, and 2 with grade 3 anorexia and grade 5 pneumonitis in the weekly PTX 30, 40, 50, and 60 mg/m² groups, respectively.
All adverse events (AE’s), except for the death in the 60 mg/m² group, showed reversible improvement, and the safety profile was deemed acceptable. The 2-year survival rate was 40.0%, and the complete response rate was 54.2%. Additionally, there was a significant difference in survival between patients with favorable and unfavorable Geriatric-8 scores.
The study concluded that a weekly dose of 50 mg/m² of PTX with concomitant radiation was well-tolerated, establishing it as the recommended dose for further investigation.
This study was funded by the Grant-in-Aid for Scientific Research (C) (40570932 to KH) from the Japan Society for the Promotion of Science (JSPS) and the Japan Agency for Medical Research and Development (AMED).
Source: https://pubmed.ncbi.nlm.nih.gov/39030570/
Hirata K, Yoshida K, Katada C, et al. (2024). “Definitive chemoradiotherapy with paclitaxel for locally advanced esophageal squamous cell carcinoma in older patients (PARADISE-1): a phase I trial.” BMC Cancer. 2024 Jul 19;24(1):873. doi: 10.1186/s12885-024-12653-4. PMID: 39030570; PMCID: PMC11264717.
