A Phase II Study of Regorafenib With a Lower Starting Dose in Patients With Metastatic Colorectal Cancer: Exposure–Toxicity Analysis of Unbound Regorafenib and Its Active Metabolites (RESET Trial)

Suzuki, Takeshi; Sukawa, Yasutaka; Imamura, Chiyo K.; Masuishi, Toshiki; Satake, Hironaga; Kumekawa, Yosuke; Funakoshi, Shinsuke; Kotaka, Masahito; Horie, Yoshiki; Kawai, Shinya; Okuda, Hiroyuki; Terazawa, Tetsuji; Kondoh, Chihiro; Kato, Ken; Yoshimura, Kenichi; Ishikawa, Hideki; Hamamoto, Yasuo; Boku, Narikazu; Takaishi, Hiromasa; Kanai, Takanori

doi:10.1016/j.clcc.2019.10.004

Cited by 22 publications

(17 citation statements)

References 21 publications

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“…However, this suggests that the optimum dose varies between individual patients and 160 mg may not be a suitable starting dose for all patients. One study that used the same starting dose of 120 mg reported that the blood concentrations of regorafenib and its metabolites were low in patients who could continue treatments after the regorafenib dose was increased from 120 to 160 mg 18 . Moreover, it has been speculated that large individual differences exist in the capacity to metabolise regorafenib.…”

Section: Laboratory Abnormalitiesmentioning

confidence: 99%

Phase II dose titration study of regorafenib in progressive unresectable metastatic colorectal cancer

Kato

Kudo

Kagawa

et al. 2023

Sci Rep

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Regorafenib has shown significant survival benefit as a salvage therapy for colorectal cancer; however, its starting dose has been controversial in recent studies. Therefore, we conducted a prospective study on the efficacy and safety of the dose reduction of regorafenib to 120 mg. Patients received 120 mg regorafenib once per day for 3 weeks, followed by a 1-week off-treatment period. The primary endpoint was the investigator-assessed disease control rate (DCR). Sixty patients were registered, and the DCR was 38.3% with a median progression-free survival of 2.5 months (95% confidence interval [CI] 1.9–3.7) and median overall survival of 10.0 months (95% CI 6.9–15.2). Common grade 3–4 adverse events were hand-foot skin reaction and hypertension (20.0% each). The results of administration of 120 mg regorafenib as the starting dose are consistent with reports from prior phase III trials, which used starting doses of 160 mg. This lower initiating dose of regorafenib may be beneficial to certain patient populations. This clinical trial was registered in the UMIN Clinical Trials Registry (UMIN-CTR number UMIN000018968, registration date: 10/09/2015).

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Section: Laboratory Abnormalitiesmentioning

confidence: 99%

Phase II dose titration study of regorafenib in progressive unresectable metastatic colorectal cancer

Kato

Kudo

Kagawa

et al. 2023

Sci Rep

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“…In this study, dose escalation to 160 mg on Day 15 was achieved in only 6/70 patients and the disease control rate was lower than expected (32.4%), suggesting that efficacy may be compromised if dose escalation is not implemented. 52 However, PFS was not reported, and this was a small study, which should therefore be interpreted with caution. The randomized, phase II REARRANGE study investigated different dosing approaches of induction (first cycle) treatment with regorafenib in patients with mCRC, including an assessment of safety, efficacy, and dose-related outcomes.…”

Section: Alternative Starting Dosesmentioning

confidence: 88%

Practical considerations in the use of regorafenib in metastatic colorectal cancer

Loupakis

Antonuzzo

Bachet³

et al. 2020

Ther Adv Med Oncol

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Over the past 20 years, management of patients with metastatic colorectal cancer (mCRC) has improved considerably, leading to increased overall survival and more patients eligible for third- or later-line therapy. Currently, two oral therapies are recommended in the third-line treatment of mCRC, regorafenib and trifluridine/tipiracil. Selecting the most appropriate treatment in the third-line setting poses different challenges compared with treatment selection at earlier stages. Therefore, it is important for physicians to understand and differentiate between available treatment options and to communicate the benefits and challenges of these to patients. In this narrative review, practical information on regorafenib is provided to aid physicians in their decision-making and patient communications in daily practice. We discuss the importance of appropriate patient selection and adverse events management through close patient monitoring and dose adjustments to ensure patients stay on treatment for longer and receive as much benefit as possible. We also highlight key physician–patient communication points to facilitate shared decision-making.

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“…In another dose-escalation study, patients who received 120 mg/d and failed to escalate to 160 mg/d showed a lower DCR (22%) than those who were escalated to 160 mg/d (75%). 30 It is not rare that both physicians and patients were unwilling to risk adverse events if a dose lower than 160 mg/d was well tolerated in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety Comparison of Regorafenib and Fruquintinib in Metastatic Colorectal Cancer-An Observational Cohort Study in the Real World

Zhang

Chen

Wang

et al. 2022

Clinical Colorectal Cancer

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A Phase II Study of Regorafenib With a Lower Starting Dose in Patients With Metastatic Colorectal Cancer: Exposure–Toxicity Analysis of Unbound Regorafenib and Its Active Metabolites (RESET Trial)

Cited by 22 publications

References 21 publications

Phase II dose titration study of regorafenib in progressive unresectable metastatic colorectal cancer

Phase II dose titration study of regorafenib in progressive unresectable metastatic colorectal cancer

Practical considerations in the use of regorafenib in metastatic colorectal cancer

Efficacy and Safety Comparison of Regorafenib and Fruquintinib in Metastatic Colorectal Cancer-An Observational Cohort Study in the Real World

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