Dataset Information

Pharmacokinetic Study of Adjuvant Gemcitabine Therapy for Biliary Tract Cancer following Major Hepatectomy (KHBO1101).

ABSTRACT: Biliary tract cancer (BTC) patients who have undergone surgical resection with major hepatectomy cannot tolerate the standard gemcitabine regimen (1,000 mg/m2 on days 1, 8, and 15 every 4 weeks) due to severe toxicities such as myelosuppression. Our dose-finding study of adjuvant gemcitabine therapy for biliary tract cancer following major hepatectomy determined that the recommended dose is 1,000 mg/m2 on days 1 and 15 every 4 weeks. Here, we evaluate the pharmacokinetics and pharmacodynamics of gemcitabine in these subjects.We evaluated BTC patients scheduled to undergo surgical resection with major hepatectomy followed by gemcitabine therapy. A pharmacokinetic evaluation of gemcitabine and its main metabolite, 2',2'-difluorodeoxyuridine (dFdU), was conducted at the initial administration of gemcitabine, which was given by intravenous infusion over 30 min at a dose of 800-1,000 mg/m2. Physical examination and adverse events were monitored for 12 weeks.Thirteen patients were enrolled from August 2011 to January 2013, with 12 ultimately completing the pharmacokinetic study. Eight patients had hilar cholangiocarcinoma, three had intrahepatic cholangiocarcinoma, and one had superficial spreading type cholangiocarcinoma. The median interval from surgery to first administration of gemcitabine was 65.5 days (range, 43-83 days). We observed the following toxicities: neutropenia (n = 11, 91.7%), leukopenia (n = 10, 83.3%), thrombocytopenia (n = 6, 50.0%), and infection (n = 5, 41.7%). Grade 3 or 4 neutropenia was observed in 25% (n = 3) of patients. There were differences in clearance of gemcitabine and dFdU between our subjects and the subjects who had not undergone hepatectomy.Major hepatectomy did not affect the pharmacokinetics of gemcitabine or dFdU.UMIN-CTR in (JPRN) UMIN000005109.

SUBMITTER: Fujiwara Y

PROVIDER: S-EPMC4669083 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pharmacokinetic Study of Adjuvant Gemcitabine Therapy for Biliary Tract Cancer following Major Hepatectomy (KHBO1101).

Fujiwara Yutaka Y Kobayashi Shogo S Nagano Hiroaki H Kanai Masashi M Hatano Etsuo E Toyoda Masanori M Ajiki Tetsuo T Takashima Yuki Y Yoshimura Kenichi K Hamada Akinobu A Minami Hironobu H Ioka Tatsuya T

PloS one 20151203 12

<h4>Background</h4>Biliary tract cancer (BTC) patients who have undergone surgical resection with major hepatectomy cannot tolerate the standard gemcitabine regimen (1,000 mg/m2 on days 1, 8, and 15 every 4 weeks) due to severe toxicities such as myelosuppression. Our dose-finding study of adjuvant gemcitabine therapy for biliary tract cancer following major hepatectomy determined that the recommended dose is 1,000 mg/m2 on days 1 and 15 every 4 weeks. Here, we evaluate the pharmacokinetics and ...[more]

PMID: 26633034

Similar Datasets

Project description:BackgroundBiliary tract cancer (BTC) is a dismal disease, even after curative intent surgery. We conducted this prospective, non-randomized phase II study to evaluate the feasibility and efficacy of cisplatin and gemcitabine as adjuvant treatment in patients with resected BTC.MethodsPatients initially received gemcitabine 1000 mg/m2 alone on days 1, 8 and 15 every 28-days for a total of six cycles (single agent cohort), and after protocol amendment a combination therapy with gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 was administered every 21 days for a total of eight cycles (combined regimen cohort). Treatment was planned to start within eight weeks after curative intent resection. Adverse events, disease-free survival and overall survival were assessed.ResultsOverall 30 patients were enrolled in the study from August 2008 and last patient was enrolled at 2nd December 2014. The follow-up of the patients ended at 31st December 2016. The first 9 patients received single-agent gemcitabine. The interim analysis met the predefined feasibility criteria and, from September 2010 on, the second group of 21 patients received the combination of cisplatin plus gemcitabine. In the single-agent cohort with gemcitabine the median relative dose intensity (RDI) was 100% (IQR 88.3-100). Patients treated with the combination cisplatin-gemcitabine received an overall median RDI of 100% (IQR 50-100) for cisplatin and 100% (IQR 75-100) for gemcitabine respectively. The most significant non-hematological adverse events (grade 3 or 4) were fatigue (20%), infections during neutropenia (10%), and two cases of biliary sepsis (7%). Abnormal liver function was seen in 10% of the patients. One patient died due to infectious complications during treatment with cisplatin and gemcitabine. The median disease-free survival (DFS) was 14.9 months (95% CI 0-33.8) with a corresponding 3-year DFS of 43.1 ± 9.1%. The median overall survival (OS) was 40.6 months (95% CI 18.8-62.3) with a 3-year OS of 55.7 ± 9.2%. No statistically significant differences in survival were seen between the two treatment cohorts.ConclusionAdjuvant chemotherapy with gemcitabine with or without cisplatin was well tolerated and resulted in promising survival of the patients.Trial registrationThe study was retrospectively registered on 25th June 2009 at clinicaltrials.gov ( NCT01073839 ).

Project description:ImportanceThe association of adjuvant chemotherapy (AC) with survival in the general population of patients with resected biliary tract cancer (BTC) remains controversial. As such, the role of this treatment in the treatment of older adult patients (aged ≥70 years) needs to be evaluated.ObjectiveTo describe the patterns of use of AC and compare survival outcomes of AC and observation in older adult patients following resection of BTC.Design, setting, and participantsThis retrospective cohort study included 8091 older adult patients with resected BTC with data available in the National Cancer Database from January 1, 2004, to December 31, 2019. Patients were divided into 2 cohorts: AC and observation. The AC cohort was subdivided into single-agent and multiagent AC treatment.ExposuresAdjuvant chemotherapy vs observation following BTC resection.Main outcomes and measuresThe primary outcome was overall survival (OS) of patients who received AC compared with observation following resection of BTC as evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Inverse probability of treatment weighting and propensity score matching were performed to address indication bias.ResultsBetween 2004 and 2019, of 8091 older adult patients with resected BTC identified (median [range] age, 77 [70-90] years; 5136 women [63.5%]; 2955 men [36.5%]), only one-third (2632 [32.5%]) received AC. There was an increase in the use of AC across the study period from 20.7% (n = 495) in 2004 to 2009 to 41.2% (n = 856) in 2016 to 2019. Age 80 years or older (odds ratio, 0.29; 95% CI, 0.25-0.33; P < .001) and gallbladder primary site (odds ratio, 0.71; 95% CI, 0.61-0.83; P < .001) were associated with a lower odds of AC. Following inverse probability of treatment weighting, as a composite, AC was not associated with improved survival (median OS, 20.5 months; 95% CI, 19.2-21.7 months) compared with observation (median OS, 19.0 months; 95% CI, 18.1-20.3 months). A longer median OS was associated with single-agent AC (21.5 months; 95% CI, 19.9-24.0 months) but not multiagent AC (19.1 months; 95% CI, 17.5-21.1 months) compared with observation (median OS, 17.3 months; 95% CI, 16.1-18.4 months). This improvement in OS with single-agent AC was not apparent on multivariable analysis (hazard ratio [HR], 0.97; 95% CI, 0.89-1.05; P = .44). However, age at diagnosis of 80 years or older (HR, 1.35; 95% CI, 1.28-1.42; P < .001) and treatment at nonacademic centers (HR, 1.14; 95% CI, 1.07-1.20, P < .001) were associated with worse OS.Conclusions and relevanceIn this cohort study of older adult patients, AC was not associated with an improvement in survival compared with observation following BTC resection. These findings suggest the need for further study of AC for older adult patients who may benefit after curative intent surgery for BTC.

Dataset Information

Pharmacokinetic Study of Adjuvant Gemcitabine Therapy for Biliary Tract Cancer following Major Hepatectomy (KHBO1101).

Publications

Pharmacokinetic Study of Adjuvant Gemcitabine Therapy for Biliary Tract Cancer following Major Hepatectomy (KHBO1101).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets