A phase II study of S-1 monotherapy administered for 2 weeks of a 3-week cycle in advanced gastric cancer patients with poor performance status.
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ABSTRACT:
SUBMITTER: Jeung HC
PROVIDER: S-EPMC2360346 | biostudies-other | 2007 Aug
REPOSITORIES: biostudies-other
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Project description:The retrospective study was conducted to evaluate the efficacy and safety of careful dose modification of apatinib as third or further-line treatment in advanced gastric cancer (aGC) patients with poor performance status (PS = 2 or 3).Patients with aGC of poor PS who had received at least 2 lines of chemotherapy were treated with apatinib at a dose of 250 mg initially and best supportive care (BSC). During the whole treatment, the dose of apatinib was adjusted according to the status of PS (group treatment). Meanwhile, patients of poor PS (PS = 2 or 3) with aGC who received BSC alone after second or further-line treatment in the recent 5 years in our institution have been investigated for their median overall survival (mOS) as control. Kaplan-Meier curve was adopted for the description of OS in the 2 groups. Univariate analysis was conducted with log-rank test between OS and the potential characteristics including gender, age, PS status, primary tumor lesion, Her-2 status, and previous lines of treatment. Toxicities were assessed with the criteria of National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.0.A total of 23 patients who received apatinib plus BSC treatment and 41 patients treated with BSC alone were reviewed in the present study. Median exposure time of apatinib was 2.4 months ranging from 0.2 to 5.1 months. The median OS in the group treatment was 4.3 months (95% CI, 2.735-5.865) comparing to the control as 2.1 months (95% CI, 1.473-2.727, P = .0004). In addition, PS status was shown as the only independently significant factor to influence the OS (P = .049). Fatigue (82.6%), appetite decrease (73.9%), and anemia (69.6%) appeared to be the most common adverse events at any grade during the therapy of apatinib.The outcomes of the present study revealed that therapeutic model of careful dose modification of apatinib therapy initiated with low dose plus BSC as third or further-line treatment might be more beneficial on survival time comparing to BSC alone in patients with aGC of poor PS, however, as well as apparent adverse events.
| S-EPMC6855580 | biostudies-literature
Project description:This paper reports the outcome of gefitinib for Chinese advanced NSCLC patients with poor performance status (PS) at the Peking Union Medical College Hospital.From Oct 2002 to Apr. 2006, 42 advanced NSCLC patients with PS 3/4 received gefitinib 250 mg/day treatment. Median survival (MS) were calculated using the Kaplan-Meier method and a Cox regression model was used to find main factors affecting MS.Adverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were rash 72.2% (26/42) and diarrhea 44.4% (26/42). The objective tumor response rate and stable disease rate were 40.5% and 26.2% respectively, and median survival(MS) of all patients was 10.1 months (95% confidential interval CI, 3.4 ~ 16.8), and progression-free survival (PFS) was 5.7 months (95% CI, 4.5 ~ 6.9). The MS were significantly related with objective response of gefitinib. Objective responses was significantly related with rashes induced with gefitinib.Our study suggest that treatment with gefitinib may be well tolerated and beneficial for Chinese patients with poor PS, and the safety and efficacy were similar to patients with good PS.
| S-EPMC2588452 | biostudies-literature
Project description:ImportanceDespite approximately 40% of patients having Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of at least 2 in the real world, most landmark clinical trials that led to the use of pembrolizumab as standard of care in advanced non-small cell lung cancer (NSCLC) excluded this group.ObjectiveTo evaluate whether an ECOG PS score of at least 2 at the start of therapy is associated with progression-free survival (PFS) and overall survival (OS) in advanced NSCLC treated with pembrolizumab monotherapy.Design, setting, and participantsThis cohort study included all consecutive patients with advanced NSCLC who underwent treatment with palliative pembrolizumab monotherapy from February 2016 to October 2019 at a single academic cancer center, with data censoring on January 15, 2020.ExposuresECOG PS score at start of therapy, with 0 and 1 indicating fully active or restricted in strenuous activity and scores of 2 and higher indicating increasing disability.Main outcomes and measuresPFS and OS, measured from initiation of pembrolizumab monotherapy.ResultsOf 74 patients (median [range] age, 68.5 [33-87] years; 36 [48.7%] women; 53 [71.6%] White individuals) with median follow-up of 19.5 (95% CI, 13.4-27.8) months, 45 (60.8%) had an ECOG PS of 0 or 1, while 29 (39.2%) had an ECOG PS of at least 2. There were no significant differences in the baseline characteristics, except in age. Compared with patients with PS scores of 0 or 1, those with PS scores of at least 2 had significantly lower disease control rates (38 [88.4%] vs 15 [53.6%]; P = .002), shorter median PFS (7.9 [95% CI, 4.6-15.4] months vs 2.3 [95% CI, 1.8-4.8] months; P = .004), and shorter median OS (23.2 [14.0 vs 35.7] months vs 4.1 [95% CI, 2.1-6.9] months; P < .001). Among those potentially eligible for subsequent cancer-directed therapy beyond pembrolizumab monotherapy, patients in the group with PS scores of at least 2 were less likely to receive it than those with PS scores of 0 or 1 (2 [8.3%] vs 14 [45.2%]; P = .003). Multivariable adjustment for baseline characteristics confirmed ECOG PS of at least 2 as an independent risk factor for worse PFS (HR, 2.02; 95% CI, 1.09-3.74; P = .03) and worse OS (HR, 2.87; 95% CI, 1.40-5.89; P = .004).Conclusions and relevanceIn this cohort study, having an ECOG PS score of at least 2 was associated with poorer prognosis for treatment of advanced NSCLC with palliative pembrolizumab monotherapy. Further prospective studies are needed to evaluate more objective and consistent measures of functional status to facilitate identification of patients with borderline performance status who may achieve durable clinical benefit from treatment with pembrolizumab monotherapy.
| S-EPMC7879233 | biostudies-literature
Project description:PurposeThere is limited information on treatment recommendations for glioblastoma patients with poor performance status. Here, we aim to evaluate the association of radiotherapy on survival in glioblastoma patients presenting with poor postoperative performance status in first-line setting.MethodsWe retrospectively analyzed data of 93 glioblastoma patients presenting with poor postoperative performance status (ECOG 2-4) at the University Hospital Zurich, Switzerland, in the years 2005-2019. A total of 43 patients received radiotherapy with or without systemic therapy in the first-line setting, whereas 50 patients received no additive local or systemic treatment after initial biopsy or resection. Overall survival was calculated from primary diagnosis and from the end of radiotherapy. In addition, factors influencing survival were analyzed.ResultsMedian overall survival from primary diagnosis was 6.2 months in the radiotherapy group (95% CI 6.2-14.8 weeks, range 2-149 weeks) and 2.3 months in the group without additive treatment (95% CI 1.3-7.4 weeks, range 0-28 weeks) (p < 0.001). This survival benefit was confirmed by landmark analyses. Factors associated with overall survival were extent of resection and administration of radiotherapy with or without systemic treatment. Median survival from end of radiotherapy was 3 months (95% CI 4.3-21.7 weeks, range 0-72 weeks), with 25.6% (n = 11) early termination of treatment and 83.7% (n = 36) requiring radiotherapy as in-patients. Performance status improved in 27.9% (n = 12) of patients after radiotherapy.ConclusionIn this retrospective single-institution analysis, radiotherapy improved overall survival in patients with poor performance status, especially in patients who were amendable to neurosurgical resection.
| S-EPMC9293860 | biostudies-literature
Project description:OBJECTIVE:Galunisertib (LY2157299 monohydrate), an inhibitor of the transforming growth factor ? (TGF?) pathway, is currently under investigation in several clinical trials involving multiple tumor types. The primary objective of this study was to assess relative bioavailability of two new galunisertib formulations developed using the roller compaction (RC) dry-milled (RCD) and RC slurry-milled (RCS) processes, compared with the existing formulation developed using the high-sheer wet granulation (HSWG) process. The secondary objective was to report the safety profile after a single dose of the three formulations. METHODS:Patients with advanced or metastatic cancer were enrolled into this single-center, 3-period, 6-sequence crossover study. Patients were assigned sequentially to 1 of 6 sequences in blocks of 6 to ensure that all 6 sequences have the same number of completers. A patient entering a sequence received a different galunisertib formulation as a single 150 mg dose orally during each of the 3 periods. Each period was separated from the next by a washout interval of at least 48 hours. Pharmacokinetic (PK) parameters, including area under curve (AUC) and Cmax, were computed using standard non-compartmentalized methods of analysis. For comparison of exposures between formulations, log-transformed AUC and Cmax values were analyzed using a linear mixed-effects model. Safety assessments included adverse event monitoring, physical examinations, and laboratory tests. RESULTS:Of the 14 patients who entered and completed the study, 13 patients were included in the final statistical analysis. AUC(0-tlast), AUC(0-48 h), and AUC(0-?) for the RC formulations and the HSWG formulation were similar. Cmax was reduced by approximately 22% and tmax was longer by at least 1.00 h for the RCD and RCS formulations compared with the HSWG formulation. The RC formulations demonstrated a safety profile after a single dose similar to the HSWG formulation. CONCLUSIONS:In this relative bioavailability study comparing galunisertib formulations after a single dose, RCD and RCS formulations had similar exposure and safety profile compared with the HSWG formulation.
| S-EPMC5147053 | biostudies-literature
Project description:This phase I study was conducted to determine the recommended phase II doses, safety profile, and antitumour activity of a combination regimen of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours. Cisplatin and epirubicin were given at fixed doses of 50 and 60 mg m(-2), respectively. The irinotecan dose was escalated at 10 mg m(-2) increments from a starting dose level of 70 mg m(-2). Epirubicin, irinotecan, and their metabolites were measured with HPLC methods. In all, 35 patients received 141 courses of treatment. Irinotecan dose was escalated in seven cohorts up to 130 mg m(-2), and then finally de-escalated to 110 mg m(-2). The dose-limiting toxicity was neutropenic fever. Nonhaematologic toxicities included mild to moderate nausea/vomiting, diarrhoea and fatigue. Of 34 patients with evaluable disease, one patient had a complete response and nine patients had partial response, yielding an overall response rate of 29.4%. Pharmacokinetic parameters of epirubicin were not affected by the sequence of drug administration. However, the AUCs of irinotecan and its metabolites were increased significantly when irinotecan and epirubicin were administered concurrently. This combination regimen has promising broad antitumour activity, and will be further evaluated in phase II studies in multiple tumour types.
| S-EPMC2376925 | biostudies-other
Project description:PURPOSE:Concurrent neuromuscular electrical stimulation (NMES) involving sub-tetanic low frequency and tetanic high frequency which targets aerobic and muscular fitness is a potential alternative to conventional exercise in cancer rehabilitation. However, its safety and feasibility in patients with advanced cancer are unknown. The aim of this feasibility study was to determine safety and feasibility and evaluate changes in functional and health-related quality of life (HR-QoL) outcomes in individuals with advanced cancer and poor performance status after concurrent NMES. These results should help inform the design of future studies. METHODS:Participants with advanced cancer and poor performance status (Eastern Cooperative Oncology Group scale ??2) (n?=?18) were recruited. The intervention included a novel NMES intervention implemented over a 4-week period. Functional exercise capacity, lower limb muscle endurance and HR-QoL were measured by 6-min walk test (6MWT), 30-s sit-to-stand (30STS) and European Organization for Research and Treatment quality of life questionnaire core-30 (EORTC QLQ C30) pre and post-intervention. Participants unable to complete the 6-min walk test completed the timed up and go test. Participant experience and the impact of the intervention on daily life were investigated through semi-structured interviews. RESULTS:Ten of 18 participants completed the intervention. No adverse events were reported. Seven of 8 participants improved 6MWT performance (2 of 2 improved timed up and go), 8 of 10 participants improved 30STS and 8 of 10 participants improved Global quality of life. Perceived benefits included improved mobility and muscle strength. CONCLUSIONS:Neuromuscular electrical stimulation appears safe and feasible in advanced cancer and may improve physical and HR-QoL outcomes. Future prospective trials are warranted to confirm these findings prior to clinical implementation in an advanced cancer setting.
| S-EPMC7547042 | biostudies-literature
Project description:BackgroundAdjuvant tegafur-gimeracil-oteracil (S-1) is commonly used for gastric cancer in Asia, and tegafur-uracil (UFT) is another oral fluoropyrimidine when S-1 is unavailable. The real-world data of adjuvant UFT has less been investigated.MethodsPatients with pathological stage II-IIIB (except T1) gastric cancer receiving adjuvant UFT or S-1 monotherapy after D2 gastrectomy were included. Usage of UFT or S-1 was based on reimbursement policy of the Taiwanese healthcare system. The characteristics, chemotherapy completion rates, and 5-year recurrence-free survival (RFS) and overall survival (OS), were compared between these two groups.ResultsFrom 2005 to 2016, 86 eligible patients were included. Most tumor characteristics were similar between the UFT group (n = 37; age 59.1 ± 13.9 years) and S-1 group (n = 49; age 56.3 ± 10.7 years), except there were significantly more Borrmann type III/IV (86.5% versus 67.3%; p = 0.047) and T4 (56.8% versus 10.2%; p < 0.001) lesions in the UFT group than in the S-1 group. The chemotherapy complete rates were similar in the two groups. The 5-year RFS was 56.1% in the UFT group and 59.6% in the S-1 group (p = 0.71), and the 5-year OS was 78.3% in the UFT group and 73.1% in the S-1 group (p = 0.48). The hazard ratio of adjuvant chemotherapy (S-1 versus UFT) on RFS was 1.25 (95% confidence interval = 0.53-2.94) when Borrmann type and T and N stages were adjusted.ConclusionsThis small cohort study showed adjuvant UFT, and S-1 monotherapy had a comparable long-term outcome for pathological stage II-IIIB gastric cancer following D2 gastrectomy.
| S-EPMC8053033 | biostudies-literature
Project description:BackgroundAmong locally advanced gastric cancer (LAGC) patients, poor response to initial neoadjuvant chemotherapy (NAC) is associated with unfavorable outcomes; however, changing the postoperative therapy regimen in this group of patients is unclear. We compared the poor responders who continued the original protocols with that of patients who switched treatment after NAC plus D2 gastrectomy.MethodsOur study included LAGC patients who achieved tumor regression grade 3 according to the American Joint Committee on Cancer/College of American Pathologists system, after NAC, between December 2006 and December 2017 at our institution. Outcomes were overall survival (OS), progression-free survival (PFS), and adverse events during postoperative treatment. The propensity score matching method was used to match patients.ResultsOverall, 160 patients were enrolled in the final analysis set, including 21 switched cases and 139 non-switched cases. A 1:2 matched cohort (21 switching vs. 42 non-switching) was generated to eliminate all confounding factors. No statistical differences were observed in OS and PFS, either in the whole patients (OS: log-rank p = 0.804; PFS: log-rank p = 0.943) or in the matched cohort (OS: log-rank p = 0.907; PFS: log-rank p = 0.670) between the two groups. Patients with changed regimens had a significantly higher rate of peripheral neurotoxicity (p = 0.045). Contrarily, a lower rate of overall adverse events was observed in the non-switching group with marginal significance (p = 0.069).ConclusionAdjusting to a non-cross-resistant regimen only by post-NAC pathological evaluation may not be sufficient for designing an effective treatment route for LAGC poor responders. Treatment change required a more scrutinized clinical track, which involved a multifaceted assessment.
| S-EPMC8591025 | biostudies-literature
Project description:BACKGROUND & AIMS:Functional status (a patient's ability to perform activities that meet basic needs, fulfill usual roles, and maintain health and well-being) has been linked to outcomes in patients with cirrhosis and can be measured by the Karnofsky performance status (KPS) scale. We investigated the association between KPS score and mortality in patients with cirrhosis. METHODS:We used the United Network for Organ Sharing database to perform a retrospective cohort study of patients listed for liver transplantation in the United States between 2005 and 2015. We used Cox proportional hazards and competing risk regression analyses to examine the association between KPS and mortality and transplantation. RESULTS:Of 79,092 patients, 44% were in KPS category A (KPS, 80%-100%), 43% were in category B (KPS, 50%-70%), and 13% were in category C (KPS, 10%-40%). Between 2005 and 2015, the proportion of patients in category A decreased from 53% to 35%, whereas the proportions in categories B and C increased from 36% to 49% and from 11% to 16%, respectively. KPS was associated with mortality: compared with patients in KPS category A, the KPS B adjusted hazard ratio (HR) was 1.14 (95% confidence interval [CI], 1.11-1.18) and the KPS C adjusted HR was 1.63 (95% CI, 1.55-1.72). KPS was also associated with liver transplantation; compared with patients in KPS category A, the KPS B adjusted HR was 1.08 (95% CI, 1.06-1.11) and the KPS C adjusted HR was 1.35 (95% CI, 1.30-1.40). In competing risk analysis, only the relationship between KPS and mortality maintained significance and directionality. These relationships were most pronounced in patients without hepatocellular carcinoma. CONCLUSIONS:Among patients with cirrhosis listed for liver transplantation, poor performance status, based on the KPS scale, is associated with increased mortality. In this population, performance status has decreased over time.
| S-EPMC4955687 | biostudies-literature