Clinical implications of polymorphisms in UDP-glucuronosyl transferase (UGT) in patients with metastatic colorectal cancer (mCRC) who were treated with oxaliplatin, irinotecan, and S-1.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 503-503
Author(s):  
Sun Young Kim ◽  
Mi Song I Jang ◽  
Hyun Mi Kim ◽  
Ji Yeon Baek ◽  
Yong Sang Hong ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Objective Response ◽  
Progression Free Survival ◽  
Drug Regimen ◽  
High Rate ◽  
Free Survival ◽  
Effective Therapeutic Option ◽  
Glucuronosyl Transferase ◽  
Intensive Regimen ◽  
Selection Of

503 Background: The three-drug regimen with oxaliplatin, irinotecan and fluoropyrimidine is an effective therapeutic option for patients with mCRC, but is associated with high rate of toxicity. Pharmacogenetic profile might be helpful for selection of proper patients for this intensive regimen. Methods: Forty-two patients were enrolled to our phase II trial and were given irinotecan 150mg/m2 plus oxaliplatin 85mg/m2 on D1 and S-1 80mg/m2/day on D1-14 every 21 days as their front-line therapy for mCRC. Genomic DNA was extracted from peripheral blood, where the presence of germline polymorphisms of UGT including UGT1A1*6, UGT1A1*28, UGT1A1*60, UGT1A6*2, and UGT1A7*3 were tested. Results: Patients with UGT1A1*6 allele had a tendency of more frequent grade 2-3 vomiting (p = 0.06) compared to those without UGT1A1*6. The presence of a haplotype containing UGT1A6*2 and UGT1A7*3 was associated with grade 2-3 vomiting (p = 0.014) and grade 2-3 diarrhea (p = 0.063). Higher objective response rate (18/20, 90%) was noted in patients without UGT1A*60 compared to those with UGT1A1*60 (11/22, 50%; p = 0.008). The absence of UGT1A1*60 was also associated with marginally improved progression-free survival (10.3 mo v 7.7 mo, p = 0.081) and overall survival (26.8 mo v 15.1 mo, p= 0.044) compared to the presence of the variant allele. Conclusions: UGT1A1*6 and a haplotype containing UGT1A6*2 and UGT1A7*3 may be associated with irinotecan-related gastrointestinal toxicities. Phenotypic association of UGT1A1*60 and efficacy of the three-drug regimen requires further investigation.

scholarly journals Efficacy of EDP ± mitotane chemotherapy in the treatment of metastatic adrenocortical carcinoma. Predictive and prognostic factors of efficacy

2021 ◽  
Vol 11 (1) ◽  
pp. 37-46
Author(s):  
Ya. A. Zhulikov ◽  
E. I. Kovalenko ◽  
V. Yu. Bohyan ◽  
M. V. Khoroshilov ◽  
M. M. Gabrava ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Adrenocortical Carcinoma ◽  
Median Overall Survival ◽  
Therapeutic Option ◽  
Objective Response ◽  
Group Versus ◽  
Progression Free Survival ◽  
Ki 67 ◽  
Free Survival ◽  
Effective Therapeutic Option

Introduction. Adrenocortical carcinoma (ACC) is an orphan disease with an unfavorable prognosis. The most effective therapeutic option in the treatment of ACC is EDP plus mitotane combination chemotherapy. However, no studies comparing the efficacy of the EDP regimen with or without mitotane have been published.Materials and methods. A retrospective analysis of health records of patients with histologically confirmed metastatic ACC, who received at least one chemotherapy cycle with EDP ± mitotane. The study included 73 patients, 49 of which received a combination of EDP and mitotane and 24 were treated with EDP chemotherapy.Results. The objective response rate was 18,4 % in the EDP + mitotane group versus 4,1 % in the EDP group. Disease control was reported in 25 (51 %) and 13 (54,2 %) patients, respectively. No significant differences were found in progression-free survival (PFS) rates between the EDP and EDP + mitotane groups; the median PFS rate was 6,5 and 6,0 months, respectively. The median overall survival (OS) in the total population was 20,9 months; no significant differences were found between the groups. However, an increase in median PFS was observed in patients who achieved a therapeutic concentration of mitotane. Moreover, the achievement of therapeutic mitotane concentrations was the only factor significantly associated with improved PFS (HR 0.44, p = 0.006). Significant unfavorable prognostic factors associated with lower OS were Ki-67 level in the primary tumor > 20 % (HR 10.5, p = 0.006) and more than 1 site of metastases (HR 3.82, p = 0.02).Conclusions. This study showed that the addition of mitotane to EDP chemotherapy does not improve the median PFS and OS in the total patient population, however, the achievement of therapeutic mitotane concentrations is significantly associated with improved progression-free survival.

scholarly journals Indicadores (Outcomes) Primários e Secundários em Ensaios Clínicos Oncológicos: Definição e Usos

2014 ◽  
Vol 27 (4) ◽  
pp. 498
Author(s):  
António Vaz-Carneiro ◽  
Ricardo Da Luz ◽  
Margarida Borges ◽  
João Costa
Keyword(s):  
Clinical Trials ◽  
Methodological Issue ◽  
Objective Response ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patient Reported ◽  
Oncology Clinical Trials ◽  
Alternative Drug ◽  
Selection Of

<strong>Introduction:</strong> The proof of efficacy from a therapeutic intervention in oncology must be defined through well conducted clinical trials. One of the most important methodological issue is the outcome selection needed to calculate measures of association allowing definition of clinical efficacy.<br /><strong>Material and Methods:</strong> We designed a narrative revision based on some of the international regulatory instructions from drug agencies, as well as consensus papers from scientific oncology societies, listing and critically assessing each outcome used in oncology clinical trials.<br /><strong>Results:</strong> We identified as being the most important outcomes in oncology trials the overall survival, the progression free survival/ disease-free survival, the toxicity, the quality of life/patient- reported outcomes and the objective response rate.<br /><strong>Discussion:</strong> The selection of the primary outcome must be based on therapeutic efficacy as well as toxicity, expected survival, alternative drug regimens and even disease prevalence.<br /><strong>Conclusion:</strong> The selection of efficacy outcomes for clinical trials in oncology is very important and its selection must be well justified, and depends on the type of disease, the patients and the drug being studied.<br /><strong>Keywords:</strong> Clinical Trials as Topic; Neoplasms; Medical Oncology; Treatment Outcome.

scholarly journals Lenvatinib and pembrolizumab in the treatment of metastatic endometrial cancer: literature review and case report

2021 ◽  
pp. 124-128
Author(s):  
A. A. Rumyantsev
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Carcinoma ◽  
Objective Response Rate ◽  
Response Rate ◽  
Therapeutic Option ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
Effective Therapeutic Option ◽  
High Level

In 2019 in Russia endometrial carcinoma was diagnosed in 27151 patients, 6820 women died from the disease. The standard of frontline therapy for patients with advanced endometrial carcinoma is platinum and taxane-based chemotherapy with satisfactory efficacy – the median progression-free survival is about 13 months, and up to 50% of patients achieve objective response to therapy. On the other hand, for patients with recurrent endometrial cancer after frontline chemotherapy the results of chemotherapy remained generally unsatisfactory, the objective response rate to standard treatment was about 10 to 15%. During the last few years there significant progress has been made in this area – studies identified a subgroup of patients with a high level of microsatellite instability (MSI-high) highly sensitive to pembrolizumab therapy. In this subset of patients, who account for up to 25% of patients with metastatic endometrial cancer, the objective response rate to pembrolizumab monotherapy is up to 57%. Further studies have shown that the addition of lenvatinib to pembrolizumab therapy may be a highly effective therapeutic option for patients without MSI-high. This article describes a clinical case of the successful therapy of a patient with platinumresistant endometrial carcinoma with a combination of pembrolizumab and lenvatinib. 

scholarly journals Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 36 ◽  
Author(s):  
Antonio Facciorusso ◽  
Mohamed A. Abd El Aziz ◽  
Rodolfo Sacco
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Adverse Events ◽  
Therapeutic Option ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sensitivity Analyses ◽  
Free Survival

Regorafenib showed promising results as a second-line agent after sorafenib failure in hepatocellular carcinoma patients. The aim of this meta-analysis was to evaluate the efficacy and safety of regorafenib in hepatocarcinoma patients. A computerized bibliographic search was performed on the main databases. The primary outcome was overall survival. Secondary outcomes were progression-free survival, tumor response, and the adverse events rate. Outcomes were pooled through a random-effects model and summary estimates were expressed in terms of median and 95% confidence interval or rates, as appropriate. One randomized-controlled trial and seven non-randomized studies with 809 patients were included. The great majority of recruited patients were in Child-Pugh A and ECOG 0 stage. Median overall survival was 11.08 months (9.46–12.71) and sensitivity analyses confirmed this finding, with a median survival ranging from 10.2 to 13.8 months. Duration of regorafenib therapy was 3.58 months, whereas median progression-free survival was 3.24 months (2.68–3.86). The pooled objective response rate was 10.1% (7.8–12.5%) while the disease control rate was 65.5% (61.3–69.7%) with no evidence of heterogeneity (I2 = 0%; Diarrhea, fatigue, and hand-foot skin reaction were the most frequent adverse events. The current meta-analysis shows that regorafenib represents a valuable and relatively safe therapeutic option in intermediate/advanced hepatocellular carcinomapatients who progress on sorafenib.

Long-Term Followup of Patients with Follicular Lymphoma (FL) Treated with Two Years of Maintenance Rituximab: Response to Rituximab Retreatment at Progression.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4723-4723 ◽  
Author(s):  
John D. Hainsworth ◽  
Christina Meng ◽  
David R. Spigel ◽  
Eric L. Raefsky ◽  
John H. Barton ◽  
...  
Keyword(s):  
Stable Disease ◽  
Therapeutic Option ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Aggressive Histology ◽  
Maintenance Schedules

Abstract Background: Maintenance treatment with rituximab prolongs progression-free survival (PFS) in patients with FL when administered following single agent rituximab, chemotherapy, or rituximab/chemotherapy combinations. However, the possible induction of lymphoma resistance by prolonged rituximab treatment has been a cause for concern. To address this issue, we obtained long-term followup on patients who had received 2 years of maintenance rituximab and had objective response or stable disease when treatment was discontinued. With a median followup of 7 years, we evaluated the subsequent course of these patients, with particular attention to: treatment administered at relapse, sensitivity to retreatment with rituximab at progression, and survival. Methods: Between March 1998 and August 2002, we treated a total of 106 patients in 2 sequential studies with single-agent rituximab, followed by rituximab maintenance therapy (repeated 4-week courses every 6 months for 2 years). In both studies (JCO20:4261, 2002; JCO23:1088JCO23:2005), rituximab maintenance was arbitrarily discontinued after 2 years. Fifty-eight of 106 patients (55%) in these 2 trials had objective response or stable disease following completion of 2 years of maintenance rituximab. Followup regarding the subsequent course and treatment was obtained in all 58 patients. Results: Nineteen of 58 patients (33%; 18% of all 106 patients treated) remain in continuous remission after a median followup of 7 years (range 4–8 years). Thirty-five patients progressed, while 4 patients died of intercurrent illnesses while in remission. Of the 35 patients who progressed, 24 patients received single-agent rituximab as the next therapy, while 2 patients received rituximab in combination with chemotherapy. Eight of 24 patients (33%) had objective responses to single-agent rituximab (CR 5, PR 3), 14 patients (58%) had stable disease, and 2 patients progressed. Six of the responding patients again received maintenance rituximab. Median PFS in the 22 responding/stable patients was 47 months (95% CI = 39–52 months) with 27% of patients progression-free at 5 years. Both patients receiving rituximab plus chemotherapy had complete remissions (durations 33, 64 months). Transformation to a more aggressive histology was not documented in any patient. The median survival of all 35 relapsing patients, measured from the time of relapse, is 63 months, (95% CI = 40-N.R.). Conclusions: The majority of patients who relapse after 2 years of maintenance rituximab therapy remain sensitive to rituximab. Retreatment with rituximab, either as a single agent or in combination with chemotherapy, is a reasonable therapeutic option at the time of progression. Further investigation of more prolonged rituximab maintenance schedules is indicated.

scholarly journals Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with Oxaliplatin, Cisplatin, and Doxorubicin in Patients with Peritoneal Carcinomatosis: An Open-Label, Single-Arm, Phase II Clinical Trial

Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 102
Author(s):  
Michele De Simone ◽  
Marco Vaira ◽  
Monica Argenziano ◽  
Paola Berchialla ◽  
Alberto Pisacane ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Systemic Chemotherapy ◽  
Single Port ◽  
Tumor Regression ◽  
Therapeutic Option ◽  
Combined Treatment ◽  
Objective Response ◽  
Progression Free Survival ◽  
Peritoneal Disease ◽  
Free Survival

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an innovative approach for treating peritoneal carcinomatosis that applies chemotherapeutic drugs into the peritoneal cavity as an under-pressure airflow. It improves local bioavailability of cytostatic drugs as compared to conventional intraperitoneal chemotherapy. The aim of this study is to prove feasibility, efficacy and safety of this new treatment. Patients included in the analysis underwent at least two single port PIPAC procedures; drugs used were Oxaliplatin for colorectal cancers and Cisplatin + Doxorubicin for ovarian, gastric, and primary peritoneal cancers. The primary endpoint was the Disease Control Rate according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Secondary significant endpoints were overall and progression free survival, tumor regression on histology, and quality of life. Safety and tolerability were assessed according to the Common Terminology Criteria for Adverse Events 4. Sixty-three patients were enrolled in this trial. Forty patients (100 PIPAC) were eligible for analysis. Twenty patients were undergoing systemic chemotherapy. Fourteen patients reported an objective response (35%). Median overall survival was 18.1 months; median progression-free survival was 7.4 months. Minor morbidity was observed in seven procedures. Grade 3 complications occurred in two patients, and grade 4 in one patient submitted to reoperation. Single-port PIPAC is feasible, safe, and easy to perform. The combined treatment based on systemic chemotherapy and PIPAC does not induce significant hepatic and renal toxicity and can be considered a valid therapeutic option in patients with advanced peritoneal disease. Further studies on the use of PIPAC alone, possibly with different drug dosages, may define the real effectiveness of the procedure.

scholarly journals Case Report: Anlotinib Therapy in a Patient With Recurrent and Metastatic RAIR-DTC Harboring Coexistent TERT Promoter and BRAFV600E Mutations

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanjun Su ◽  
Shaohao Cheng ◽  
Jun Qian ◽  
Min Zhang ◽  
Tuanli Li ◽  
...  
Keyword(s):  
Differentiated Thyroid Cancer ◽  
Radioactive Iodine ◽  
Treatment Cycle ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Open Label ◽  
Free Survival ◽  
Tert Promoter ◽  
Effective Therapeutic Option ◽  
Favorable Clinical Outcome

We describe a case of recurrent and metastatic radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) treated with anlotinib in this report. The patient was randomized to placebo initially, after disease progressed at C8 (C is the treatment cycle), the patient was referred to the open label therapy of anlotinib, 12 mg p.o. daily with a 2-week on/1-week off regimen. Partial response was achieved at C2 with anlotinib treatment. To date, over 37 months of progression-free survival (PFS) has been achieved. Adverse effects were tolerable and manageable in this patient. Molecular characterization revealed coexistent C228T mutation of TERT promoter and BRAFV600E mutations. Favorable clinical outcome in this patient suggests that anlotinib might provide a novel effective therapeutic option for patients with RAIR-DTC. TERT and BRAFV600E mutations may represent as biomarker for predicting salutary effects of anlotinib.

scholarly journals CTIM-03. PHASE II STUDY OF REGORAFENIB IN BEVACIZUMAB REFRACTORY RECURRENT GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii33-ii33
Author(s):  
Yasmeen Rauf ◽  
Cathy Schilero ◽  
David Peereboom ◽  
Manmeet Ahluwalia
Keyword(s):  
Dose Escalation ◽  
Therapeutic Option ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Weekly Dose ◽  
Cellular Functions ◽  
Molecule Inhibitor ◽  
Secondary Endpoints ◽  
Magnetic Resonance Imaging Mri

Abstract BACKGROUND Most patients with glioblastoma (GBM) receive bevacizumab as part of their treatment. There is no good therapeutic option after bevacizumab failure. Regorafenib has potent preclinical antitumor activity and long-lasting anti-angiogenic activity as measured by dynamic contrast enhanced (DCE) – magnetic resonance imaging (MRI). Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment. METHODS Patients with progression of GBM after treatment with Bevacizumab will be eligible for the study. Oral administration of Regorafenib at 160 mg once daily will be administered for 3 weeks on /1 week off. Weekly dose escalation of regorafenib from 80 mg to 160 mg/day will be employed as per the Redos strategy. Patients start the treatment 80 mg/day in week 1, with weekly dose escalation to 120 mg in week 2, then 160 mg week in 3 if no significant drug-related toxicities are observed. They will be continued on treatment with Regorafenib 160 md /day till tumor progression or toxicity. They will get MRI brain every 4 weeks during the study. RESULTS Primary endpoint is median Overall survival. Secondary endpoints include progression free survival at 6 months and the median time to progression and objective response rate using the modified RANO criteria. The overall safety and tolerability of regorafenib by CTCAE version 5.0. will also be reported. CONCLUSION This is an ongoing clinical trial.

scholarly journals RTID-05. INDIGO: A GLOBAL, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF VORASIDENIB (AG-881) VS PLACEBO IN PATIENTS WITH RESIDUAL/RECURRENT GRADE II GLIOMA WITH AN ISOCITRATE DEHYDROGENASE 1/2 (IDH1/2) MUTATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii194-ii194
Author(s):  
Ingo Mellinghoff ◽  
Martin van den Bent ◽  
Jennifer Clarke ◽  
Elizabeth Maher ◽  
Katherine Peters ◽  
...  
Keyword(s):  
High Risk ◽  
Dose Escalation ◽  
Objective Response ◽  
Data Monitoring Committee ◽  
Progression Free Survival ◽  
High Risk Population ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival ◽  
Grade Ii

Abstract BACKGROUND Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study. METHODS Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).

scholarly journals Effectiveness of nivolumab affected by prior cetuximab use and neck dissection in Japanese patients with recurrent or metastatic head and neck cancer: results from a retrospective observational study in a real-world setting

2021 ◽  
Author(s):  
Shin Kariya ◽  
Yasushi Shimizu ◽  
Nobuhiro Hanai ◽  
Ryuji Yasumatsu ◽  
Tomoya Yokota ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Dissection ◽  
Neck Cancer ◽  
Median Overall Survival ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Free Survival

Abstract Background To examine the effect of prior use of cetuximab and neck dissection on the effectiveness of nivolumab, we conducted a large-scale subgroup analysis in Japanese patients with recurrent/metastatic head and neck cancer. Methods Data on the effectiveness of nivolumab were extracted from patient medical records. All patients were analyzed for effectiveness by prior cetuximab use. In the analyses for prior neck dissection, only patients with locally advanced disease were included. Results Of 256 patients analyzed, 155 had received prior cetuximab. Nineteen of 50 patients with local recurrence underwent neck dissection. The objective response rate was 14.7 vs 17.2% (p = 0.6116), median progression-free survival was 2.0 vs 3.1 months (p = 0.0261), and median overall survival was 8.4 vs 12 months (p = 0.0548) with vs without prior cetuximab use, respectively. The objective response rate was 23.1 vs 25.9% (p = 0.8455), median progression-free survival was 1.8 vs 3.0 months (p = 0.6650), and median overall survival was 9.1 vs 9.9 months (p = 0.5289) with vs without neck dissection, respectively. Conclusions These findings support the use of nivolumab for patients with recurrent/metastatic head and neck cancer regardless of prior cetuximab use or neck dissection history. Trial registration number UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436)

Sign in / Sign up

Export Citation Format

Share Document