The impact of starting dose with or without subsequent dose escalation of liposomal irinotecan on treatment outcomes in patients with metastatic pancreatic ductal adenocarcinoma

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

The impact of starting dose with or without subsequent dose escalation of liposomal irinotecan on treatment outcomes in patients with metastatic pancreatic ductal adenocarcinoma

Am J Cancer Res. 2022 Nov 15;12(11):5062-5073. eCollection 2022.

Authors

Nai-Jung Chiang^{1

2}, Yan-Shen Shan³, Chung-Pin Li^{1

4

5}, Shih-Hung Yang⁶, Yung-Yeh Su⁷, Sz-Chi Chiu⁸, Li-Yuan Bai⁹, Shih-Chang Chuang¹⁰, De-Chuan Chan¹¹, Chia-Jui Yen¹², Cheng-Ming Peng¹³, Tai-Jan Chiu¹⁴, Yen-Yang Chen¹⁴, Jen-Shi Chen¹⁵, Wen-Chi Chou¹⁵

Affiliations

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

PMID: 36504882
PMCID: PMC9729898

Abstract

Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) improves survival in patients with pancreatic ductal adenocarcinoma (PDAC) after progression to gemcitabine-based therapy. Few studies have examined whether the starting dose and dose escalation of nal-IRI in subsequent treatment cycles may influence patient outcomes and toxicity profiles. A total of 667 patients who received nal-IRI + 5-FU/LV for PDAC treatment between August 2018 and November 2020 at nine medical centers in Taiwan were included and retrospectively analyzed. Patients were allocated to the standard starting dose (SD), reduced starting dose (RD) without escalation, and RD with escalation of nal-IRI groups for comparison of survival outcome and safety. Propensity score matching (PSM) was performed to adjust for possible confounding variables. Nal-IRI was prescribed at SD, RD without escalation, and RD with escalation in 465 (69.7%), 147 (22.0), and 55 (8.2%), respectively. RD with escalation patients had significantly longer treatment cycles (6, range 2-25) than SD (5, range 1-42, P<0.001) and RD without escalation patients (4, range 1-26, P<0.001). The median overall survival (OS) of the patients were as follows: SD, 6.2 months (95% confidence interval [CI], 5.7-6.7); RD with escalation, 7.6 months (95% CI, 6.1-9.2); and RD without escalation, 3.6 months (95% CI, 2.6-4.5). After PSM to adjust for potential confounders, RD without escalation patients still had the poorest OS compared to the other two groups (P<0.001), while the OS difference between SD and RD with escalation patients was insignificant (P=0.10). SD patients had higher incidences of ≥ grade 3 neutropenia and febrile neutropenia than the other two groups. Administering nal-IRI at RD followed by dose escalation in subsequent treatment cycles is safe and does not compromise survival outcomes in selected patients with PDAC receiving nal-IRI plus 5-FU/LV.

Keywords: Pre-emptive dose reduction; dose escalation; drug compliance; nanoliposomal irinotecan; tolerance.