Phase II Study of Nab-Paclitaxel and Cisplatin with Radiotherapy in Advanced ESCC

Overview

This Phase II single-arm study evaluated the safety and efficacy of weekly nab-paclitaxel (75 mg/m²) combined with cisplatin (25 mg/m²) and concurrent radiotherapy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). The regimen demonstrated promising therapeutic activity with manageable toxicity profiles, suggesting a potential alternative to conventional chemoradiotherapy.

Background

Oesophageal squamous cell carcinoma is a highly aggressive malignancy with poor prognosis due to late-stage diagnosis and limited effective treatments. Standard concurrent chemoradiotherapy using cisplatin and 5-fluorouracil has suboptimal efficacy and significant toxicity. Paclitaxel shows radiosensitizing properties but is limited by hypersensitivity and neurotoxicity. Nanoparticle albumin-bound paclitaxel (nab-PTX) offers improved tissue penetration and reduced toxicity, warranting investigation in combination with cisplatin and radiotherapy for locally advanced ESCC.

Data Highlights

The Phase II study administered nab-paclitaxel at 75 mg/m² and cisplatin at 25 mg/m² weekly on days 1, 8, 15, 22, and 29 alongside intensity-modulated radiotherapy (50–64 Gy in 25–32 fractions). Patients were selected based on strict inclusion criteria including clinical stage I to IVA ESCC without distant metastases. Treatment discontinuation criteria included severe toxicities or tumour-related complications. The study was registered (ChiCTR1900021079) and ethically approved.

Key Findings

• Nab-paclitaxel combined with cisplatin and radiotherapy was well tolerated with manageable hematologic and non-hematologic toxicities.
• The regimen achieved a high overall response rate, indicating promising antitumor activity in locally advanced ESCC.
• Weekly dosing of nab-paclitaxel at 75 mg/m² was selected based on Phase I pharmacokinetic and toxicological data, balancing efficacy and safety.
• Intensity-modulated radiotherapy targeting the gross tumour volume and involved lymph nodes was effectively integrated with chemotherapy.
• Strict criteria for treatment discontinuation ensured patient safety in the event of severe adverse events such as oesophageal fistula or haemorrhage.

Clinical Implications

This study supports the use of nab-paclitaxel plus cisplatin concurrent with radiotherapy as a feasible and effective treatment option for patients with locally advanced ESCC. The regimen may offer improved tolerability compared to traditional cisplatin and 5-fluorouracil combinations, potentially enhancing patient compliance and outcomes. Careful monitoring for toxicities and adherence to discontinuation criteria remain essential.

Conclusion

Nab-paclitaxel combined with cisplatin and radiotherapy demonstrates promising efficacy and manageable safety in locally advanced ESCC, warranting further investigation in larger controlled trials. This approach may represent a valuable alternative to existing chemoradiotherapy regimens.

References

1. Radiation Therapy Oncology Group Studies -- Standard CCRT for ESCC
2. Preclinical and Clinical Studies on Paclitaxel and Nab-Paclitaxel in ESCC
3. Phase I Dose Escalation Study of Nab-Paclitaxel and Cisplatin with Radiotherapy