Efficacy and safety of SOXIRI versus mFOLFIRINOX in advanced pancreatic cancer

Abstract

Background: Modified fluorouracil/leucovorin/irinotecan/oxaliplatin (FOLFIRINOX) regimen (mFOLFIRINOX), comprised of fluorouracil, leucovorin, irinotecan and oxaliplatin, is the first-line standard chemotherapy in patients with advanced pancreatic cancer. The S-1/oxaliplatin/irinotecan (SOXIRI) regimen has also been studied recently under similar conditions. This study compared its efficacy and safety. Methods: All cases of locally advanced or metastatic pancreatic cancer treated with the SOXIRI or mFOLFIRINOX regimen in Sun Yat-sen University Cancer Centre from July 2012 to June 2021 were reviewed retrospectively. The data of patients who satisfied the inclusion criteria were compared between two cohorts, including overall survival (OS), progression-free survival (PFS), objective response rate, disease control rate and safety. Results: A total of 198 patients were enrolled in the study, including 102 patients treated with SOXIRI and 96 patients treated with mFOLFIRINOX. There was no significant difference in OS [12.1 months versus 11.2 months, hazard ratio (HR) = 1.04, p = 0.81] or PFS (6.5 months versus 6.8 months, HR = 0.99, p = 0.96) between patients treated with SOXIRI and mFOLFIRINOX. In the subgroup analysis, patients with slightly elevated baseline total bilirubin (TBIL) or underweight patients before chemotherapy were more likely to have a longer OS or PFS from SOXIRI than from mFOLFIRINOX. In addition, the carbohydrate antigen (CA)19-9 decline was a good predictor for the efficacy and prognosis of both chemotherapy regimens. All grade adverse events were parallel in all kinds of toxicities except that anaemia was more common in the SOXIRI group than in the mFOLFIRINOX group (41.4% versus 24%, p = 0.03). The occurrence of any grade 3 to 4 toxicity was similar in the two groups. Conclusions: For locally advanced or metastatic pancreatic cancer patients, the SOXIRI regimen had similar efficacy and controllable safety compared with the mFOLFIRINOX regimen.

Advancing perspectives on the off-label use of anticancer drugs: an updated classification and exploration of categories

“…Additionally, it is not possible to fully explore all new categories of antineoplastic drugs for off-label use because the clinical requirements are intricate and varied, such as the requirements of patients with advanced cancer, multiple diseases, adherence, affordability, and tolerability, physician decision-making, and the same drug from different manufacturers or different specifications and dosage forms from the same manufacturer, which can also lead to the unapproved use of antineoplastic drug. Nevertheless, to promote the standardized management and rational use of unapproved anticancer drugs, the scope of categories on unapproved antineoplastic drug use can be further extended from electronic medical records, patient-reported outcome studies (Khan and Butler, 2022), and the real-world database from China (Wang et al, 2023).…”

“…Pembrolizumab is administered at a dose of 100 mg (2 mg/kg) instead of the fixed dose of 200 mg in combination chemotherapy (the KEYNOTE-001 study illustrated that the dose range of pembrolizumab is 0.005 mg/kg~10 mg/kg, with maximum antitumor activity achieved at 2 mg/kg, and pembrolizumab administered through weight-based dosing and fixed-dose regimens had comparable pharmacokinetics [PK]) (Chatterjee et al, 2016). Pembrolizumab could potentially decrease the potential financial toxicity if given with PK guidance in patients with advanced NSCLC (Wang et al, 2023). As for the different levels of expression of dosing, a fixed dose of trastuzumab was prescribed instead of the dose adjusted for body weight in practice (Levêque, 2008;Pivot et al, 2017); ii) unlicensed frequency (lower), where the regimen consists of capecitabine (2,000 mg/m 2 once daily on days 1-14 of each 21-day cycle) in combination with lapatinib (1,250 mg/d).…”

“…For instance, the prescribing instructions for vincristine recommend reducing the dosage by 50% when the patient's serum bilirubin level is above 3 mg/dL. (Motzer et al, 2012;Eroglu and Fruehauf, 2013;Gore et al, 2019;Benson et al, 2021;Ajani et al, 2022Ajani et al, , 2023Horwitz et al, 2022;Huang et al, 2022;Ren et al, 2022;Li et al, 2023) Extended indications with the same cancer type…”

“…Prescribing an approved anticancer drug beyond its licensed indications should be subdivided into two sectors: i) expanding to different cancer types, for example, oxaliplatin is approved for colorectal cancer but used for non-Hodgkin’s lymphoma, esophageal cancer, biliary tract cancer, stomach cancer, ovarian cancer, pancreatic cancer, NSCLC, testicular cancer, transitional cell carcinoma of the bladder, and hepatocellular carcinoma in clinical practice ( Motzer et al, 2012 ; Eroglu and Fruehauf, 2013 ; Gore et al, 2019 ; Benson et al, 2021 ; Ajani et al, 2022 , 2023 ; Horwitz et al, 2022 ; Huang et al, 2022 ; Ren et al, 2022 ; Li et al, 2023 ) and ii) expanding to a different stage (oxaliplatin with 5-Fu/calcium folinate is used as adjuvant therapy for stage II colon cancer in adults) ( Baxter et al, 2022 ), subtype (trastuzumab for HER2-negative rather than HER2-positive breast cancer) ( Ignatiadis et al, 2018 ), or treatment line of the same cancer type (pyrotinib switched from second-line to the first-line treatment for advanced HER2-positive metastatic breast cancer) ( Xu et al, 2022 ). Regorafenib is approved for second-line therapy but used as a first-line agent alone for advanced hepatocellular carcinoma ( Bai et al, 2023 ).…”