Dataset Information

Impact of Ninjin'Yoeito on Fatigue in Patients Receiving Nab-Paclitaxel Plus Gemcitabine Therapy: A Prospective, Single-Arm, Phase II Open Label, Nonrandomized, Historically-Controlled Study.

ABSTRACT:

Background

Ninjin'yoeito, a traditional Japanese herbal medicine, is used to prevent fatigue, loss of appetite, and coldness of limbs. Fatigue is an especially common issue during chemotherapy and can affect quality of life and the ability to complete scheduled treatment.

Objectives

This prospective exploratory trial evaluates the efficacy of ninjin'yoeito for fatigue in patients undergoing nab-paclitaxel plus gemcitabine therapy for unresectable pancreatic cancer. The primary end point was evaluation of fatigue according to Functional Assessment of Chronic Illness Therapy-Fatigue score during 2 courses of nab-paclitaxel plus gemcitabine therapy. Secondary end points included evaluation of dose intensity, appetite loss using numerical rating scale, and peripheral neuropathy using a patient neurotoxicity questionnaire.

Methods

We compared data from this interventional trial with a prior observational trial without administration of ninjin'yoeito with identical definition of end points (UMIN000021758). Thirty patients were required by the study.

Results

Threshold mean of Functional Assessment of Chronic Illness Therapy-Fatigue score across 8 weeks during chemotherapy was under 5.3 (P = 0.002). Secondary end points did not reveal any specific patterns in appetite loss or degree of pain. No significant changes in patient neurotoxicity questionnaire concerning sensory/motor disorders were observed, but the mean (SD) incidence of patients with sensory disturbance was higher between the fifth and eighth weeks (8.8 [1.26]) than during the first and fourth weeks (4.8 [0.96]) (P = 0.003). Clinically significant adverse reactions of ninjin'yoeito were not observed.

Conclusions

Ninjin'yoeito may be useful for improving the symptoms of fatigue caused by nab-paclitaxel plus gemcitabine in patients with unresectable pancreatic cancer. UMIN Clinical Trials Registry identifier: UMIN000025606. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

SUBMITTER: Okada KI

PROVIDER: S-EPMC7522496 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of <i>Ninjin'Yoeito</i> on Fatigue in Patients Receiving Nab-Paclitaxel Plus Gemcitabine Therapy: A Prospective, Single-Arm, Phase II Open Label, Nonrandomized, Historically-Controlled Study.

Okada Ken-Ichi KI Kawai Manabu M Hirono Seiko S Miyazawa Motoki M Kitahata Yuji Y Kobayashi Ryohei R Ueno Masaki M Hayami Shinya S Shimokawa Toshio T Yamaue Hiroki H

Current therapeutic research, clinical and experimental 20200915

<h4>Background</h4><i>Ninjin'yoeito</i>, a traditional Japanese herbal medicine, is used to prevent fatigue, loss of appetite, and coldness of limbs. Fatigue is an especially common issue during chemotherapy and can affect quality of life and the ability to complete scheduled treatment.<h4>Objectives</h4>This prospective exploratory trial evaluates the efficacy of <i>ninjin'yoeito</i> for fatigue in patients undergoing nab-paclitaxel plus gemcitabine therapy for unresectable pancreatic cancer. T ...[more]

PMID: 33014206

Similar Datasets

Project description:BackgroundIn a phase 1-2 trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine, substantial clinical activity was noted in patients with advanced pancreatic cancer. We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer.MethodsWe randomly assigned patients with a Karnofsky performance-status score of 70 or more (on a scale from 0 to 100, with higher scores indicating better performance status) to nab-paclitaxel (125 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter) on days 1, 8, and 15 every 4 weeks or gemcitabine monotherapy (1000 mg per square meter) weekly for 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles). Patients received the study treatment until disease progression. The primary end point was overall survival; secondary end points were progression-free survival and overall response rate.ResultsA total of 861 patients were randomly assigned to nab-paclitaxel plus gemcitabine (431 patients) or gemcitabine (430). The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P<0.001). The survival rate was 35% in the nab-paclitaxel-gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years. The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group, as compared with 3.7 months in the gemcitabine group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; P<0.001); the response rate according to independent review was 23% versus 7% in the two groups (P<0.001). The most common adverse events of grade 3 or higher were neutropenia (38% in the nab-paclitaxel-gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile neutropenia occurred in 3% versus 1% of the patients in the two groups. In the nab-paclitaxel-gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days.ConclusionsIn patients with metastatic pancreatic adenocarcinoma, nab-paclitaxel plus gemcitabine significantly improved overall survival, progression-free survival, and response rate, but rates of peripheral neuropathy and myelosuppression were increased. (Funded by Celgene; ClinicalTrials.gov number, NCT00844649.).

Project description:BackgroundPancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following first-line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab-paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions.MethodsThe study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice.ResultsAG was well-tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second-line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first-line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first-line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second-line OS and PFS.ConclusionsThis study represents the largest real-world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first-line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first-line therapy.

Project description:BackgroundCompared with normal cells, tumour cells contain elevated levels of reactive oxygen species (ROS). Increased levels of the antioxidant protein NAD(P)H:quinone oxidoreductase 1 (NQO1) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) correlate negatively with the survival of patients with pancreatic cancer. Napabucasin is an investigational, orally administered ROS generator bioactivated by NQO1.MethodsIn the open-label, phase 3 CanStem111P study (NCT02993731), adults with previously untreated metastatic pancreatic adenocarcinoma (mPDAC) were randomised (1:1) to napabucasin plus nab-paclitaxel with gemcitabine or nab-paclitaxel with gemcitabine alone. The primary endpoint was overall survival (OS). In exploratory analyses, OS was evaluated in the subgroup of patients with tumours positive for pSTAT3 (biomarker-positive).FindingsBetween 30 January 2017 and 20 February 2019, a total of 1779 patients were screened across 165 study sites in Austria, Australia, Belgium, Canada, China, Czech Republic, France, Germany, Italy, Japan, Korea, Netherlands, Poland, Portugal, Russia, Singapore, Spain, Taiwan, Ukraine, and the US. Of the 565 and 569 patients randomised to the napabucasin and control treatment arms, respectively, 206 and 176 were biomarker-positive. Median (95% confidence interval [CI]) OS in the napabucasin and control treatment arms was 11.4 (10.5-12.2) and 11.7 (10.7-12.7) months, respectively (hazard ratio, 1.07; 95% CI, 0.93-1.23). Due to the lack of OS improvement in the napabucasin arm, CanStem111P was terminated due to futility. In the biomarker-positive subgroup, no difference between treatment arms was found for OS. Grade ≥3 adverse events were reported in 85.4% and 83.9% of napabucasin-treated and control-treated patients, respectively. The incidence of gastrointestinal-related grade ≥3 events was higher with napabucasin (diarrhoea: 11.6% vs 4.9%; abdominal pain: 10.0% vs 4.8%).InterpretationOur findings suggested that although the addition of napabucasin to nab-paclitaxel with gemcitabine did not improve efficacy in patients with previously untreated mPDAC, the safety profile of napabucasin was consistent with previous reports. CanStem111P represents the largest cohort of patients with mPDAC administered nab-paclitaxel with gemcitabine in the clinical trial setting. Our data reinforce the value of nab-paclitaxel plus gemcitabine as a platform for novel therapeutics approaches in mPDAC.FundingThe Sumitomo Pharma Oncology, Inc.