Response to Y. Sasaki <i>et al</i>.: Is repeating <scp>FOLFIRINOX</scp> in the original dosage and treatment schedule tolerable in Japanese patients with pancreatic cancer?

Okusaka, Takuji; Ikeda, Masafumi; Fukutomi, Akira; Ioka, Tatsuya; Furuse, Junji; Ohkawa, Shinichi; Isayama, Hiroyuki; Boku, Narikazu

doi:10.1111/cas.12709

Cited by 4 publications

(2 citation statements)

References 9 publications

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“…Treatment-emergent grade 3-4 AEs were not unexpected and were similar to those previously reported for gemcitabine in this disease group, including fatigue, hematological toxicity and altered liver function enzymes. 1,12 The ORR (ITT) was 33% and efficacy evaluable ORR was 44%, compared to 26.1% reported in the ABC-02 study for the cisplatin/gemcitabine combination. 1 Tumour control and OS in ABC-08 were 76% and 9.6 months (with an upper 95% CI of 13.1 months) respectively, similar to the cisplatin/ gemcitabine combination in ABC-02: 81.4% and 11.7 months.…”

Section: Discussionmentioning

confidence: 86%

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A Phase Ib Study of NUC-1031 in Combination with Cisplatin for the First-Line Treatment of Patients with Advanced Biliary Tract Cancer (ABC-08)

et al. 2020

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Background. Cisplatin/gemcitabine is standard 1st-line treatment for patients with advanced biliary tract cancer (ABC). NUC-1031 (phosphoramidate transformation of gemcitabine) is designed to enhance efficacy by maximising intra-tumoural active metabolites. Methods. Patients with untreated ABC, ECOG-PS 0-1 received NUC-1031 (625 or 725mg/m 2) and cisplatin (25mg/m 2) on days 1 and 8, every 21 days. Objectives: safety and maximum tolerated dose (primary); and ORR, pharmacokinetics, PFS and OS (secondary). Results. Twenty-one patients (median age 61 years, n=13 male; 17 cholangiocarcinoma, 2 ampullary and 2 gallbladder cancer) received NUC-1031 625mg/m 2 (n=8 and expansion n=7; median 6 cycles) or 725mg/m 2 (n=6; median 7.5 cycles). Treatment was well tolerated; most common treatment-emergent grade 3-4 adverse-events occurring in >1 patient with 625mg/m 2 NUC-1031 were increased GGT: 40%, ALT: 20%, bilirubin: 13%, neutropenia: 27%, decreased WCC: 20%, thrombocytopenia: 13%, nausea: 13%, diarrhea: 13%, fatigue: 13%, and thrombus: 20% and with 725mg/m 2 , increased GGT: 67% and fatigue: 33%. NUC-1031 725mg/m 2 was selected as the recommended dose with cisplatin in ABC. ORR: 33% (1 CR, 6 PRs), DCR 76%, median PFS 7.2 months (95%-CI 4.3-10.1), median OS 9.6 months (95%-CI 6.7-13.1). The median plasma AUC 0-24 and C max estimates were highest for NUC-1031 (218-324 μg•h/mL and 309-889 μg/mL, respectively) and lowest for dFdC (0.47-1.56 μg•h/ mL and 0.284-0.522 μg/mL, respectively). Conclusions. This is the first study reporting on the combination of NUC-1031 with cisplatin in ABC and demonstrated a favourable safety profile; 725mg/m 2 NUC-1031 in combination with cisplatin is undergoing phase III trial evaluation in ABC.

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Section: Discussionmentioning

confidence: 86%

“…The median number (range) of received cycles was 6 (1-12) for the cohort that received 625mg/m 2 NUC-1031 (n=15) and 7.5 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) for the 725mg/m 2 NUC-1031 dose (n=6) in combination with cisplatin (day 1 and 8 of a 21-day schedule).…”

Section: Efficacymentioning

confidence: 99%

A Phase Ib Study of NUC-1031 in Combination with Cisplatin for the First-Line Treatment of Patients with Advanced Biliary Tract Cancer (ABC-08)

et al. 2020

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Cure of unresectable, locally advanced pancreatic cancer after multidisciplinary therapy

Kao

Liu

Shan

et al. 2018

Journal of Cancer Research and Practice

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Deciphering Potential Role of Hippo Signaling Pathway in Breast Cancer: A Comprehensive Review

Bhavnagari,

Raval,

Shah

2023

CPD

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Breast cancer is a heterogeneous disease and a leading malignancy around the world. It is a vital cause of untimely mortality among women. Drug resistance is the major challenge for effective cancer therapeutics. In contrast, cancer stem cells (CSCs) are one of the reasons for drug resistance, tumor progression, and metastasis. The small population of CSCs present in each tumor has the ability of self-renewal, differentiation, and tumorigenicity. CSCs are often identified and enriched using a variety of cell surface markers (CD44, CD24, CD133, ABCG2, CD49f, LGR5, SSEA-3, CD70) that exert their functions by different regulatory networks, i.e., Notch, Wnt/β-catenin, hedgehog (Hh), and Hippo signaling pathways. Particularly the Hippo signaling pathway is the emerging and very less explored cancer stem cell pathway. Here, in this review, the Hippo signaling molecules are elaborated with respect to their ability of stemness as epigenetic modulators and how these molecules can be targeted for better cancer treatment and to overcome drug resistance.

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Response to Y. Sasaki et al.: Is repeating FOLFIRINOX in the original dosage and treatment schedule tolerable in Japanese patients with pancreatic cancer?

Cited by 4 publications

References 9 publications

A Phase Ib Study of NUC-1031 in Combination with Cisplatin for the First-Line Treatment of Patients with Advanced Biliary Tract Cancer (ABC-08)

A Phase Ib Study of NUC-1031 in Combination with Cisplatin for the First-Line Treatment of Patients with Advanced Biliary Tract Cancer (ABC-08)

Cure of unresectable, locally advanced pancreatic cancer after multidisciplinary therapy

Deciphering Potential Role of Hippo Signaling Pathway in Breast Cancer: A Comprehensive Review

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