Best Supportive Care Compared With Chemotherapy for Unresectable Gall Bladder Cancer: A Randomized Controlled Study

2010 ◽  
Vol 28 (30) ◽  
pp. 4581-4586 ◽  
Author(s):  
Atul Sharma ◽  
Amit Dutt Dwary ◽  
Bidhu Kalyan Mohanti ◽  
Surya V. Deo ◽  
Sujoy Pal ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Gall Bladder ◽  
Supportive Care ◽  
Controlled Trial ◽  
Randomized Study ◽  
Best Supportive Care ◽  
Gall Bladder Cancer ◽  
Controlled Study ◽  
Randomized Controlled ◽  
Grade 3

Purpose We designed this study to evaluate efficacy of modified gemcitabine and oxaliplatin (mGEMOX) over best supportive care (BSC) or fluorouracil (FU) and folinic acid (FA) in unresectable gall bladder cancer (GBC). Patients and Methods Patients with unresectable GBC were enrolled for single center randomized study. Arm A, BSC; arm B, FU 425 mg/m2 and FA 20 mg/m2 intravenous (IV) bolus weekly for 30 weeks (FUFA); arm C, gemcitabine 900 mg/m2 and oxaliplatin 80 mg/m2 IV infusion on days 1 and 8 every 3 weeks for maximum of six cycles. Eighty-one patients were randomly assigned, arms A (n = 27), B (n = 28), and C (n = 26). Results Complete response plus partial response in the three groups was 0 (0%), four (14.3%), and eight (30.8%) respectively (P < .001). Two patients in the mGEMOX arm and one patient in the FUFA arm underwent curative resection after chemotherapy. One patient in the mGEMOX arm had complete pathologic response. Median overall survival (OS) was 4.5, 4.6, and 9.5 months for the BSC, FUFA, and mGEMOX arms (P = .039), respectively. Progression-free survival (PFS) was 2.8, 3.5, and 8.5 months for the three groups (P < .001). There was no difference in grade 3/4 toxicities in the chemotherapy arms except transaminitis, which was more prevalent in mGEMOX arm (P = .04). Two patients in the FUFA arm and 10 patients in the mGEMOX arm had grade 3 or 4 myelosuppression. Two patients in the mGEMOX group had neutropenic fever that resolved with antibiotics. Conclusion This randomized controlled trial confirmed the efficacy of chemotherapy (mGEMOX) compared with BSC and FUFA in improving OS and PFS in unresectable GBC.

A randomized controlled trial comparing modified gemcitabine plus oxaliplatin (mGEMOX) to gemcitabine plus cisplatin in the management of unresectable gall bladder cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4162-TPS4162
Author(s):  
Atul Sharma ◽  
Surendra Pal Chaudhary ◽  
N. K. Shukla ◽  
B. K. Mohanti ◽  
S. V. S. Deo ◽  
...  
Keyword(s):  
Gall Bladder ◽  
Supportive Care ◽  
Biliary Tract ◽  
Controlled Trial ◽  
Treatment Protocol ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Controlled Study ◽  
Randomized Controlled ◽  
Gemcitabine And Cisplatin

TPS4162 Background: In a recently conducted study we have shown that combination of gemcitabine and oxaliplatin is superior to 5 fluorouracil and leucoverine or best supportive care. (Sharma A, Dwary AD, Mohanti BK,et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer:A randomized controlled study. J Clin Oncol. 2010; 28: 4581-4586.) In another recent publication from UK, gemcitabine and cisplatin combination was found superior to gemcitabine alone in biliary tract cancers (J W Valle, HS Wasan, DD Palmer, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Eng J Med. 2010;362:1273-1281.).The current study is being planned to see whether the combination of gemcitabine and oxaliplatin is equivalent (equivalence study) to gemcitabine and cisplatin in these patients. Methods: Primary end point of the study is overall survival in subjects receiving mGEMOX or GemCis regimen. Secondary end points are: a) Comparison of progression free survival in 2 groups; b) Response rates in two groups; c) Identification of genes predictive of responses in a subset of patients; d) To evaluate role of PET CT in GBC patients predicting disease activity. Sample size was calculated taking median survival of 9.5 months in our previous study with mGEMOX and 11.7 months with GemCis. For this total of 216 patients are required (108 in each arm); to make for major protocol violation and lost to follow up additional 22 patients in each arm will be enrolled. Thus in total 260 patients (130) in each arm will be recruited. This will have alpha and beta values of 0.05 and 0.20 respectively. So far 103 patients have been enrolled and interim analysis is being planned. Treatment protocol: Cycles will be repeated every 3 weeks. Arm A- mGEMOX. Inj Oxaliplatin 80 mg/m22 hours infusion in Dextrose 5% Day 1 and 8. Inj Gemcitabine 900 mg/m2IV 30 minutes infusion day 1 and 8 maximum of 6 cycles. Arm B- GEMCIS. Inj Cisplatin 25 mg/m2PO Days 1 and 8. Inj Gemcitabine 1000 mg/m2IV 30 minutes infusion day1and 8 maximum of 8 cycles. Clinical trial information: CTRI/2010/091/001406.

scholarly journals Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nicholas G. Nickols ◽  
Matthew B. Goetz ◽  
Christopher J. Graber ◽  
Debika Bhattacharya ◽  
Guy Soo Hoo ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Supportive Care ◽  
Controlled Trial ◽  
Best Supportive Care ◽  
Phase 2 ◽  
Lung Epithelium ◽  
Therapeutic Targeting ◽  
Randomized Controlled ◽  
Lhrh Antagonist ◽  
Cell Surface Protease

Abstract Background Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity. Methods This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3–5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated. Discussion In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19. Trial registration ClinicalTrials.gov NCT04397718. Registered on May 21, 2020

scholarly journals Total Intravenous Anesthesia Maintained the Degree of Pre-Existing Mitral Regurgitation Better than Isoflurane Anesthesia in Cardiac Surgery: A Randomized Controlled Trial

2019 ◽  
Vol 8 (8) ◽  
pp. 1104 ◽  
Author(s):  
Ahn ◽  
Ahn ◽  
Yi
Keyword(s):  
Cardiac Surgery ◽  
Mitral Regurgitation ◽  
Controlled Trial ◽  
Tertiary Care ◽  
Total Intravenous Anesthesia ◽  
Controlled Study ◽  
Intravenous Anesthesia ◽  
Isoflurane Anesthesia ◽  
Randomized Controlled ◽  
Grade 3

Accurate assessment of mitral regurgitation (MR) is critical during mitral valve repair surgery. However, anesthesia may influence the degree of mitral regurgitation by changing pre- and after-load or cardiac contractility. Therefore, we compared changes in mitral regurgitation by total intravenous anesthesia (TIVA) and inhalation anesthesia in patients with pre-existing mitral regurgitation. This was a double-blind randomized controlled study conducted at a tertiary care center in 2018. Fifty-four mitral regurgitation patents undergoing elective cardiac surgery were randomly assigned to receive TIVA or isoflurane. Primary endpoint was change of regurgitation volume by anesthesia. The reduction of regurgitation volume by anesthesia was greater in the isoflurane group than in the TIVA group (mean (95% confidence interval CI): −0.20 (−6.15, 5.75) vs. −9.66 (−15.77, −3.56), mL·beat−1, p = 0.0266) and this phenomenon was more prominent with severe mitral regurgitation (grade 3 or 4) (mean (95% CI): −0.33 (−9.10, 8.44) vs. −16.20 (−24.22, −8.18), mL·beat−1, p = 0.0079). Among patients with MR grade 3 or 4, 94% remained the same with TIVA during anesthesia compared to 56% with isoflurane. In conclusion, TIVA maintained the pre-anesthetic state of mitral regurgitation relatively well, while the severity of mitral regurgitation tended to decrease with isoflurane anesthesia.

Capecitabine therapy in advanced gall bladder cancer: A phase II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14153-14153
Author(s):  
Q. Chowdhury ◽  
S. Reza ◽  
M. Hai ◽  
S. Shahid
Keyword(s):  
Bladder Cancer ◽  
Gall Bladder ◽  
Phase Ii ◽  
Gall Bladder Cancer ◽  
Radio Therapy ◽  
Before And After ◽  
Hand Foot Syndrome ◽  
History Of ◽  
Grade 3 ◽  
Advanced Gall Bladder Cancer

14153 Background: Thymidine phosphorylase (TP) activity is found at higher levels in gall bladder cancer (GBC) tissues than in adjacent healthy tissues. GBC is relatively sensitive to 5-FU. TP activated capecitabine (CAP) mimics the continuous infusion of 5-FU. In view of drug potentiality this present study was initiated. Our aim was to evaluate the therapeutic efficacy and safety of CAP in previously untreated GBC patients (Pts). Methods: It was an open-labelled, single-centred, non-randomised and prospective study. Outcome measures were response rate and type of response for efficacy measurement and safety was measured by adverse events & laboratory blood values (LBV). All LBV were within reference range at baseline. The patients had no prior chemo/ radio therapy or a family history of malignancy; adenocarcinoma (stage III–IV); age 40–70 yrs; male/female: 16/ 30; KPS ≥ 70%. 46 pts were treated with 306 cycles (min 3–max 12) of CAP at a dose of 2500 mg/day in two divided doses from day 1–14 followed by 1-week rest. Results: Median age was 50 yrs. Hand foot syndrome occurred in 17.39% pts, diarrhoea (grade 3 & 4) 21.75% and both 15.21%, all toxicities were manageable. Mean LBV before and after CAP therapy were hemoglobin: 11.38–0.35 g/dl (95% CI, 10.66–2.10); total count of WBC: 9,260–580/mm3 (95% CI, 8,680–9,840); platelet count: 251,000–2,000/mm3 (95% CI, 227,000–275,000) and serum bilirubin: 1.17–0.33 mg/dl (95% CI, 0.5–1.84). The LBV between baseline and after CAP therapy were not statistically significant. Partial response was found in 12 pts (26.08%), stable disease in 26 pts (56.21%), and progressive disease in 8 pts (17.39%). Mean KPS value after therapy was 76% (95% CI, 69–84). Conclusion: This clinical experience indicates that CAP is a convenient choice in phase II chemo naïve GBC pts not adversely affecting haematological values. No significant financial relationships to disclose.

scholarly journals Safety, Tolerability, and Immunogenicity of Plasmodium falciparum Sporozoite Vaccine Administered by Direct Venous Inoculation to Infants and Young Children: Findings From an Age De-escalation, Dose-Escalation, Double-blind, Randomized Controlled Study in Western Kenya

2019 ◽  
Vol 71 (4) ◽  
pp. 1063-1071 ◽  
Author(s):  
Laura C Steinhardt ◽  
Thomas L Richie ◽  
Reuben Yego ◽  
Dorcas Akach ◽  
Mary J Hamel ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dose Escalation ◽  
Controlled Trial ◽  
Safety Data ◽  
Controlled Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Western Kenya ◽  
Randomized Controlled ◽  
Falciparum Sporozoite ◽  
Grade 3

Abstract Background The whole Plasmodium falciparum sporozoite (PfSPZ) vaccine is being evaluated for malaria prevention. The vaccine is administered intravenously for maximal efficacy. Direct venous inoculation (DVI) with PfSPZ vaccine has been safe, tolerable, and feasible in adults, but safety data for children and infants are limited. Methods We conducted an age de-escalation, dose-escalation randomized controlled trial in Siaya County, western Kenya. Children and infants (aged 5–9 years, 13–59 months, and 5–12 months) were enrolled into 13 age-dose cohorts of 12 participants and randomized 2:1 to vaccine or normal saline placebo in escalating doses: 1.35 × 105, 2.7 × 105, 4.5 × 105, 9.0 × 105, and 1.8 × 106 PfSPZ, with the 2 highest doses given twice, 8 weeks apart. Solicited adverse events (AEs) were monitored for 8 days after vaccination, unsolicited AEs for 29 days, and serious AEs throughout the study. Blood taken prevaccination and 1 week postvaccination was tested for immunoglobulin G antibodies to P. falciparum circumsporozoite protein (PfCSP) using enzyme-linked immunosorbent assay. Results Rates of AEs were similar in vaccinees and controls for solicited (35.7% vs 41.5%) and unsolicited (83.9% vs 92.5%) AEs, respectively. No related grade 3 AEs, serious AEs, or grade 3 laboratory abnormalities occurred. Most (79.0%) vaccinations were administered by a single DVI. Among those in the 9.0 × 105 and 1.8 × 106 PfSPZ groups, 36 of 45 (80.0%) vaccinees and 4 of 21 (19.0%) placebo controls developed antibodies to PfCSP (P &lt; .001). Conclusions PfSPZ vaccine in doses as high as 1.8 × 106 can be administered to infants and children by DVI, and was safe, well tolerated, and immunogenic. Clinical Trials Registration NCT02687373.

Jab1-siRNA Induces Cell Growth Inhibition and Cell Cycle Arrest in Gall Bladder Cancer Cells via Targeting Jab1 Signalosome

2020 ◽  
Vol 19 (16) ◽  
pp. 2019-2033 ◽  
Author(s):  
Pratibha Pandey ◽  
Mohammad H. Siddiqui ◽  
Anu Behari ◽  
Vinay K. Kapoor ◽  
Kumudesh Mishra ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cell Growth ◽  
Gall Bladder ◽  
Growth Inhibition ◽  
Cell Cycle Arrest ◽  
Gall Bladder Cancer ◽  
Cell Growth Inhibition ◽  
Cycle Arrest ◽  
Apoptotic Induction

Background: The aberrant alteration in Jab1 signalosome (COP9 Signalosome Complex Subunit 5) has been proven to be associated with the progression of several carcinomas. However the specific role and mechanism of action of Jab1 signalosome in carcinogenesis of gall bladder cancer (GBC) are poorly understood. Objective: The main objective of our study was to elucidate the role and mechanism of Jab1 signalosome in gall bladder cancer by employing siRNA. Methods: Jab1 overexpression was identified in gall bladder cancer tissue sample. The role of Jab1-siRNA approach in cell growth inhibition and apoptotic induction was then examined by RT-PCR, Western Blotting, MTT, ROS, Hoechst and FITC/Annexin-V staining. Results: In the current study, we have shown that overexpression of Jab1 stimulated the proliferation of GBC cells; whereas downregulation of Jab1 by using Jab1-siRNA approach resulted incell growth inhibition and apoptotic induction. Furthermore, we found that downregulation of Jab1 induces cell cycle arrest at G1 phase and upregulated the expression of p27, p53 and Bax gene. Moreover, Jab1-siRNA induces apoptosis by enhancing ROS generation and caspase-3 activation. In addition, combined treatment with Jab1-siRNA and gemicitabine demonstrated an enhanced decline in cell proliferation which further suggested increased efficacy of gemcitabine at a very lower dose (5μM) in combination with Jab1-siRNA. Conclusion: In conclusion, our study strongly suggests that targeting Jab1 signalosome could be a promising therapeutic target for the treatment of gall bladder cancer.

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