Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres Followed by Gemcitabine plus Cisplatin for Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Single-Arm Multicenter Clinical Trial

Stephen Lam Chan; Chanisa Chotipanich; Su Pin Choo; Su Wen Kwang; Frankie Mo; Akeanong Worakitsitisatorn; David Tai; Raghav Sundar; David Chee Eng Ng; Kelvin Siu Hoong Loke; Leung Li; Kelvin Kwok Chai Ng; Yong Wei Peng; Simon Chun-Ho Yu

doi:10.1159/000525489

Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres Followed by Gemcitabine plus Cisplatin for Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Single-Arm Multicenter Clinical Trial

Liver Cancer. 2022 Jun 15;11(5):451-459. doi: 10.1159/000525489. eCollection 2022 Sep.

Authors

Stephen Lam Chan^{1

2

3}, Chanisa Chotipanich⁴, Su Pin Choo⁵, Su Wen Kwang⁶, Frankie Mo¹, Akeanong Worakitsitisatorn⁷, David Tai⁸, Raghav Sundar^{9

10}, David Chee Eng Ng¹¹, Kelvin Siu Hoong Loke¹¹, Leung Li¹, Kelvin Kwok Chai Ng¹², Yong Wei Peng⁹, Simon Chun-Ho Yu^{13

14}

Affiliations

¹ Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.
² State Key Laboratory of Translational Oncology, Hong Kong SAR, China.
³ Hand-in-Hand Cancer Foundation, Hong Kong SAR, China.
⁴ National Cyclotron and PET Centre, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand.
⁵ Curie Oncology and National Cancer Centre Singapore, Singapore, Singapore.
⁶ Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre, Singapore, Singapore.
⁷ Division of Intervention Radiology, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand.
⁸ Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.
⁹ Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore.
¹⁰ Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
¹¹ Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, DUKE-NUS Singhealth, Singapore, Singapore.
¹² Department of Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China.
¹³ Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.
¹⁴ Vascular and Interventional Radiology Foundation Clinical Science Centre, The Chinese University of Hong Kong, Hong Kong SAR, China.

Abstract

Introduction: This investigator-initiated clinical trial aims to study the efficacy and safety of administering selective internal radiation therapy with resin yttrium-90 microspheres (SIRT) followed by standard chemotherapy in unresectable intrahepatic cholangiocarcinoma (ICC).

Methods: A phase 2 single-arm multicenter study was conducted in patients with unresectable ICC (NCT02167711). SIRT was administered at dose of 120 Gy targeted at tumor followed by commencement of gemcitabine 1,000 mg/m² and cisplatin 25 mg/m² on days one and eight of a 21-day cycle. The primary endpoint was overall survival (OS), and the secondary endpoints include progression-free survival (PFS), response rate according to Response Evaluation Criteria in solid tumors 1.1, toxicity, and time from SIRT to commencement of chemotherapy.

Results: Total 31 patients were screened and twenty-four were recruited. All patients completed SIRT and 16 of them underwent subsequent chemotherapy. The median cycle of chemotherapy was 5 (range: 1-8). The median OS was 13.6 months (95% CI: 5.4-21.6) for the intent-to-treat population. Among 16 patients undergoing chemotherapy, the median OS was 21.6 months (95% CI: 7.3-25.2) and the median PFS was 9 months (95% CI: 3.2-13.1). The response rate was 25% (95% CI: 3.8-46.2%), and the disease control rate was 75% (95% CI: 53.8-96.2%). No new safety signal was observed, with fewer than 10% of patients suffering from grade 3 or higher treatment-related adverse events. The median time from SIRT to chemotherapy was 29 (range: 7-42) days. Eight patients could not receive chemotherapy due to rapid progressive disease (n = 4), underlying treatment unrelated comorbidities (n = 2), and withdrawal of consent due to personal reasons (n = 2).

Conclusions: Treatment of SIRT followed by standard gemcitabine and cisplatin chemotherapy is feasible and effective for unresectable ICC. Further studies are required to study the optimal sequence of SIRT and chemotherapy.

Keywords: Bile duct cancer; Chemotherapy; Combination; Liver neoplasms; Radiotherapy.