Dosing Pattern and Early Cumulative Dose of Liposomal Irinotecan in Metastatic Pancreatic Cancer: A Real-World Multicenter Study

Yung-Yeh Su; Nai-Jung Chiang; Chung-Pin Li; Chia-Jui Yen; Shih-Hung Yang; Wen-Chi Chou; Jen-Shi Chen; Tai-Jan Chiu; Yen-Yang Chen; Shih-Chang Chuang; Li-Yuan Bai; Chang-Fang Chiu; Cheng-Ming Peng; De-Chuan Chan; Sz-Chi Chiu; Yi-Hsin Yang; Yan-Shen Shan; Li-Tzong Chen

doi:10.3389/fonc.2022.800842

Dosing Pattern and Early Cumulative Dose of Liposomal Irinotecan in Metastatic Pancreatic Cancer: A Real-World Multicenter Study

Front Oncol. 2022 Jun 22:12:800842. doi: 10.3389/fonc.2022.800842. eCollection 2022.

Authors

Yung-Yeh Su^{1

2

3}, Nai-Jung Chiang^{1

4

5}, Chung-Pin Li^{5

6

7}, Chia-Jui Yen², Shih-Hung Yang⁸, Wen-Chi Chou⁹, Jen-Shi Chen⁹, Tai-Jan Chiu¹⁰, Yen-Yang Chen¹⁰, Shih-Chang Chuang^{11

12}, Li-Yuan Bai^{13

14}, Chang-Fang Chiu^{13

14

15}, Cheng-Ming Peng¹⁶, De-Chuan Chan¹⁷, Sz-Chi Chiu¹⁸, Yi-Hsin Yang¹, Yan-Shen Shan^{3

19}, Li-Tzong Chen^{1

2

20

21}

Affiliations

¹ National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
² Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁴ Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
⁵ School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁶ Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan.
⁷ Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁸ Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
⁹ Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
¹⁰ Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan.
¹¹ Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
¹² Department of Surgery, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹³ Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, and China Medical University, Taichung, Taiwan.
¹⁴ College of Medicine, School of Medicine, China Medical University, Taichung, Taiwan.
¹⁵ Cancer Center, China Medical University Hospital, Taichung, Taiwan.
¹⁶ Department of Surgery, Chung Shan Medical University Hospital and Chung Shan Medical University, Taichung, Taiwan.
¹⁷ Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
¹⁸ Department of Sales and Marketing, PharmaEngine, Inc., Taipei, Taiwan.
¹⁹ Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
²⁰ Department of Internal Medicine, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
²¹ Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.

Abstract

Introduction: This multicenter, real-world cohort study aimed to evaluate the effectiveness of early cumulative dose administration and dosing pattern of liposomal irinotecan plus fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with gemcitabine-refractory metastatic pancreatic ductal adenocarcinoma (mPDAC).

Material and methods: The electronic medical records of mPDAC patients treated with nal-IRI+5-FU/LV in nine participating centers were manually reviewed. To accommodate to the NAPOLI-1 study population, only patients with an Eastern Cooperative Oncology Group Performance Score of 0-1 were included. The survival impact of the relative 6-week cumulative dose and dosing pattern (standard vs. reduced starting dose, with and without further dose modification) were investigated.

Results: Of the 473 included patients, their median overall survival (mOS) was 6.8 [95% CI, 6.2-7.7] months. The mOS of patients who received a relative 6-week cumulative dose of >80%, 60%-80%, and <60% were 7.9, 8.2, and 4.3 months, respectively (p<0.0001). Their survival impact remained significant after covariate adjustment using Cox regression. The mOS was 8.0-8.2 months in patients with a standard starting dose with and without early dose modification, and 9.3 and 6.7 months in those who had a reduced starting dose with and without escalation in the subsequent treatment, respectively. The incidence of grade 3-4 neutropenia and diarrhea was 23.3% and 2.7%, respectively.

Conclusion: Our results support the use of nal-IRI+5-FU/LV in gemcitabine-refractory mPDAC and suggest that a lower starting dose followed by a re-escalation strategy could achieve clinical outcomes comparable to those with standard starting doses in real-world practice.

Keywords: dose escalation strategy; dose intensity; nal-IRI; pancreatic cancer; real world.