The significance of relative dose intensity in adjuvant chemotherapy of pancreatic ductal adenocarcinoma—including the analysis of clinicopathological factors influencing relative dose intensity

Yabusaki, Norimitsu; Fujii, Tsutomu; Yamada, Suguru; Murotani, Kenta; Sugimoto, Hiroyuki; Kanda, Mitsuro; Nakayama, Goro; Koike, Masahiko; Fujiwara, Michitaka; Kodera, Yasuhiro

doi:10.1097/md.0000000000004282

Cited by 35 publications

(31 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The practicality of relative dose intensity (RDI), calculated as the percentage of the delivered DI divided by the standard DI, has been shown to be an indicator of the treatment intensity of anticancer drugs [7]. The correlations between RDI and therapeutic efficacy were reported in various types of cancers, including breast cancer [8], pancreatic ductal adenocarcinoma [9], renal cell carcinoma [10], malignant lymphoma [11], and HCC [12]. However, since lenvatinib is the first oral MTA that is dosed by the patient's weight (8 mg once a day for patients weighing <60 kg or 12 mg once a day for those weighing ≥60 kg), RDI may not accurately reflect the actual treatment intensity, as is demonstrated in the following examples.Case 1: A 170 cm tall patient weighing 60 kg.…”

mentioning

confidence: 99%

Dose Intensity/Body Surface Area Ratio is a Novel Marker Useful for Predicting Response to Lenvatinib against Hepatocellular Carcinoma

Eso

Nakano

Mishima

et al. 2019

Cancers

View full text Add to dashboard Cite

Lenvatinib was recently approved as a novel first-line molecular targeted agent (MTA) for treating hepatocellular carcinoma (HCC). The importance of relative dose intensity (RDI) has been shown in the treatment of various types of cancers. However, RDI may not accurately reflect the treatment intensity of lenvatinib, as it is the first oral MTA where the dose is based on the patient's weight. We aimed to evaluate the utility of 2M-DBR (the delivered dose intensity/body surface area ratio at 60 days) by comparing the relationship between 2M-DBR, 2M-RDI (RDI at 60 days), and the therapeutic response. The therapeutic response to lenvatinib was evaluated in 45 patients who underwent computed tomography 8-12 weeks after treatment initiation. We also investigated the clinical factors associated with high 2M-DBR. The area under the receiver operating characteristic of 2M-DBR that predicts the response to lenvatinib was higher than that of 2M-RDI (0.8004 vs. 0.7778). Patients with high 2M-DBR achieved significantly better objective responses and disease control rates than those with low 2M-DBR (p < 0.0001 and 0.0008). Patients with high 2M-DBR experienced significantly longer progression-free survival (PFS) than those with low 2M-DBR (p = 0.0001), while there was no significant correlation between 2M-RDI levels and PFS (p = 0.2198). Patients who achieved higher levels of 2M-DBR had a significantly better modified ALBI grade (p = 0.0437), better CONUT score (p = 0.0222), and higher BTR (p = 0.0281). Multivariate analysis revealed that high 2M-DBR was the only significant factor associated with longer PFS. In conclusion, 2M-DBR could be an important factor that reflects treatment intensity and useful for predicting the response to lenvatinib against HCC, instead of 2M-RDI.Cancers 2020, 12, 49 2 of 12 based on the two Phase III studies [4,5]. However, due to its various adverse events (AEs) and limited efficacy, identification of novel MTA compounds has been required. Recently, lenvatinib (Lenvima ® , Eisai Co., Ltd., Tokyo, Japan) was approved as a novel first-line MTA for unresectable HCC in the EU, USA, and Asia, including Japan, China, Korea, and Taiwan, based on the Phase III REFLECT trial [6].In order to optimize and maximize the therapeutic effects of pharmacotherapy, especially in the case of anticancer drug treatment, it is essential to appropriately evaluate the patient's condition before administration, sufficiently manage AEs after initiation, and keep the dose intensity (DI) high. The practicality of relative dose intensity (RDI), calculated as the percentage of the delivered DI divided by the standard DI, has been shown to be an indicator of the treatment intensity of anticancer drugs [7]. The correlations between RDI and therapeutic efficacy were reported in various types of cancers, including breast cancer [8], pancreatic ductal adenocarcinoma [9], renal cell carcinoma [10], malignant lymphoma [11], and HCC [12]. However, since lenvatinib is the first oral MTA that is dosed by the patient's weight (8 mg once...

show abstract

mentioning

confidence: 99%

Dose Intensity/Body Surface Area Ratio is a Novel Marker Useful for Predicting Response to Lenvatinib against Hepatocellular Carcinoma

Eso

Nakano

Mishima

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…However, a significant difference was seen in cumulative adjuvant chemotherapy dose. Cumulative adjuvant chemotherapy dose has been reported as significantly related to survival in patients with potentially resectable pancreatic cancer under a surgery-first approach (27). Moreover, most cases of recurrence in this study involved distant metastasis, suggesting the necessity of sufficient adjuvant chemotherapy.…”

Section: Discussionmentioning

confidence: 61%

A Prospective Study of Intensity-modified Radiation Therapy in Comparison with Conventional 3D-RT for BR Pancreatic Cancer Patients with Arterial Involvement

Masui

Takaori

Anazawa

et al. 2017

View full text Add to dashboard Cite

show abstract

“…High RDI clinically correlates with better prognosis of various cancers [ 10 , 14 ]. Focusing on S-1, RDI > 80% is associated with better prognosis [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…In fact, the occurrence of bone marrow suppression depends on the level of exposure to chemotherapeutic agents [ 9 ]. Relative dose intensity (RDI) is a marker of the exposure of chemotherapeutic agents, and RDI > 80% is associated with anti-tumor effects of S-1 [ 10 , 11 ]. However, there are limited data regarding the relationship between bone marrow suppression induced by S-1 and RDI.…”

Section: Introductionmentioning

confidence: 99%

Impact of relative dose intensity on bone marrow suppression induced by S-1: retrospective observational study

Hirai

Ogawa

Yamaga

et al. 2018

J Pharm Health Care Sci

View full text Add to dashboard Cite

BackgroundS-1 (a combination of tegafur, gimeracil, and oteracil) is used to treat various cancers. Bone marrow suppression is a dose-limiting toxicity of S-1. The relationship between relative dose intensity (RDI) and bone marrow suppression has not been investigated. Hence, we aimed to elucidate the threshold for RDI to identify bone marrow suppression induced by S-1.MethodsIn this retrospective cohort study, patients who initiated S-1 treatment at Tokyo Women’s Medical University, Medical Center East between June 2015 and June 2017 were included. Bone marrow suppression induced by S-1 was assessed using Common Terminology Criteria for Adverse Events version 4.0. The relationships between grade 3 or higher bone marrow suppression induced by S-1 and RDIs (i.e., 70, 75, and 80%) were investigated using the multivariate Cox proportional hazard model.ResultsWe identified 143 patients in this study. The median RDI was 78.8%. Bone marrow suppression induced by S-1 developed in 19 (13.3%) patients. The multivariate Cox proportional hazard model revealed that grade ≥ 2 lymphocytopenia was associated with bone marrow suppression induced by S-1 regardless of the threshold for RDI. In addition, RDI > 75% [hazard ratio (HR) = 1.71, p < 0.05] and RDI > 80% (HR = 1.65, p < 0.05) were associated with bone marrow suppression induced by S-1.ConclusionsReduced dose of S-1 still has the risk of developing bone marrow suppression. Clinicians should assess RDI to identify high risk patients with bone marrow suppression induced by S-1.

show abstract

The significance of relative dose intensity in adjuvant chemotherapy of pancreatic ductal adenocarcinoma—including the analysis of clinicopathological factors influencing relative dose intensity

Abstract: Supplemental Digital Content is available in the text

Cited by 35 publications

References 36 publications

Dose Intensity/Body Surface Area Ratio is a Novel Marker Useful for Predicting Response to Lenvatinib against Hepatocellular Carcinoma

Dose Intensity/Body Surface Area Ratio is a Novel Marker Useful for Predicting Response to Lenvatinib against Hepatocellular Carcinoma

A Prospective Study of Intensity-modified Radiation Therapy in Comparison with Conventional 3D-RT for BR Pancreatic Cancer Patients with Arterial Involvement

Impact of relative dose intensity on bone marrow suppression induced by S-1: retrospective observational study

Contact Info

Product

Resources

About