A multi-institution phase II study of gemcitabine/cisplatin/S-1 (GCS) combination chemotherapy for patients with advanced biliary tract cancer (KHBO 1002)

Kanai, Masashi; Hatano, Etsuro; Kobayashi, Shogo; Fujiwara, Yutaka; Marubashi, Shigeru; Miyamoto, Atsushi; Shiomi, Hiroya; Kubo, Shoji; Ikuta, Shinichi; Yanagimoto, Hiroaki; Terajima, Hiroaki; Ikoma, Hisashi; Sakai, Daisuke; Kodama, Yuzo; Seo, Satoru; Morita, Satoshi; Ajiki, Tetsuo; Nagano, Hiroaki; Ioka, Tatsuya

doi:10.1007/s00280-014-2648-9

Cited by 48 publications

(40 citation statements)

References 26 publications

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“…A phase II study demonstrated significantly prolonged MST (16.2 months, 95% confidence interval 10.2–22.2 months) without uncontrollable adverse events compared with that of the ABC-02 study (11.7 months, hazard ratio = 0.64; P<0.001). Interestingly, two patients (4%) were able to achieve curative secondary resection after tumor downstaging following chemotherapy (8). Thus, GCS combination therapy should not only be considered to be a standard first-line chemotherapy, but also a ‘conversion surgery or neoadjuvant chemotherapy’.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Kanai et al determined the optimal dose of GC/S-1 (GCS) combination therapy for patients with advanced BTC in a phase I study (7) and reported a promising MST of >15 months in a phase II study (8). Based on these results, a phase III randomized trial is underway to demonstrate the superiority of GCS therapy compared with GC in patients with unresectable BTC (UMIN000014371/NCT02182778).…”

Section: Introductionmentioning

confidence: 99%

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Histological complete response in a patient with advanced biliary tract cancer treated by gemcitabine/cisplatin/S-1 combination chemotherapy: A case report

Matsubara

Nishida

Tomimaru

et al. 2016

Molecular and Clinical Oncology

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A 68-year-old woman was referred to our hospital with increased levels of biliary enzymes. On imaging, the patient was diagnosed with unresectable intrahepatic biliary tract cancer (BTC) with invasion of the portal vein and para-aortic lymph node metastasis (cT3N1M1, cStage IVb) and underwent endoscopic biliary drainage for the biliary stricture prior to therapy. The patient was subsequently enrolled in a phase III randomized trial (UMIN000014371/NCT02182778) and randomly assigned to receive gemcitabine/cisplatin/S-1 (GCS) combination therapy intravenously at doses of 1,000 or 25 mg/m2 on day 1 and orally twice daily at a dose of 80 mg/m2 on days 1–7 every 2 weeks. After 12 cycles of scheduled therapy without uncontrollable adverse effects, the patient achieved a good partial response with chemotherapy. Computed tomography (CT) revealed a marked reduction of the primary and metastatic lesions. In addition,18F-fluorodeoxyglucose-positron emission tomography/CT revealed diminishing abnormal uptake and no macroscopic evidence of factors adversely affecting tumor resectability. Therefore, the patient underwent extended right hepatic lobectomy, lymph node dissection and left hepaticojejunostomy. Finally, histological examination of the resected tissues revealed no residual cancer cells, suggesting a pathologically complete response. We herein present the case of a patient with intrahepatic BTC who achieved a pathologically complete response following combination chemotherapy with GCS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Histological complete response in a patient with advanced biliary tract cancer treated by gemcitabine/cisplatin/S-1 combination chemotherapy: A case report

Matsubara

Nishida

Tomimaru

et al. 2016

Molecular and Clinical Oncology

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“…In previous phase I and II studies, a biweekly schedule of GPS combination therapy has already been evaluated in ABTC patients . However, the dose in the biweekly regimen may not have reached the maximum tolerated dose in the previous phase I study.…”

Section: Discussionmentioning

confidence: 99%

“…Several phase I and II studies have evaluated the effectiveness of gemcitabine with platinum and FU in ABTC patients . The main grade 3 or higher toxicities were neutropenia (24–32%) and thrombocytopenia (7–33%), and a few grade 3 or higher non‐hematological toxicities were reported.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, this regimen showed promising antitumor activity, with a best response rate of 50%, median PFS of 7.4 months, and median OS of 11.2 months. In previous phase I and II studies, a biweekly schedule of GPS combination therapy has already been evaluated in ABTC patients [16,17]. However, the dose in the biweekly regimen may not have reached the maximum tolerated dose in the previous phase I study.…”

Section: Discussionmentioning

confidence: 99%

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Phase I study of gemcitabine, cisplatin, and S-1 combination therapy for patients with untreated advanced biliary tract cancer

Moriwaki

Ishida

Araki

et al. 2015

J Hepatobiliary Pancreat Sci

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Genetic analysis in the clinical management of biliary tract cancer

Wakai

Nagahashi

Shimada

et al. 2020

Annals of Gastroent Surgery

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Biliary tract cancer (BTC) is clinically and pathologically heterogeneous and responds inadequately to treatment. A small section of patients develop resectable disease, although the relapse rates are high; the benefits of adjuvant capecitabine chemotherapy for BTC are now understood, and gemcitabine‐based combination chemotherapy is the first line of therapeutic strategy for BTC; however, alternative therapy for BTC is not known. Genomic profiling can provide detailed information regarding the carcinogenesis, identification, and therapy for BTC. Currently, confirmed restorative targets for BTC are lacking. In this review, we aimed to analyze the preclinical and clinical implications of a spectrum of genomic alterations associated with new potentially remedial targets. We focused on eight draggable genes for BTC, which were described as having evidence of therapeutic impact (evidence level 2A‐3B) based on the clinical practice guidance for next‐generation sequencing in cancer diagnosis and treatment; these include ERBB2, NTRK1, RNF43, CDK6, CDKN2B, FGFR2, IDH1, and IDH2. Moreover, some of the BTC present microsatellite instability, hypermutation, and germline variants, which we also reviewed. Finally, we discussed the therapeutic options based on the next‐generation sequencing findings in BTC. Studies have demonstrated that BTC includes subgroups with individually distinct driver mutations, most of which will be targeted with new treatment plans.

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A multi-institution phase II study of gemcitabine/cisplatin/S-1 (GCS) combination chemotherapy for patients with advanced biliary tract cancer (KHBO 1002)

Cited by 48 publications

References 26 publications

Histological complete response in a patient with advanced biliary tract cancer treated by gemcitabine/cisplatin/S-1 combination chemotherapy: A case report

Histological complete response in a patient with advanced biliary tract cancer treated by gemcitabine/cisplatin/S-1 combination chemotherapy: A case report

Phase I study of gemcitabine, cisplatin, and S-1 combination therapy for patients with untreated advanced biliary tract cancer

Genetic analysis in the clinical management of biliary tract cancer

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