Representation of peritoneal metastases in published clinical trials of metastatic colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 725-725
Author(s):  
Jennifer Tseng ◽  
Darren S Bryan ◽  
Elizabeth Poli ◽  
Manish Sharma ◽  
Blase N. Polite ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Evaluation Criteria ◽  
Peritoneal Metastases ◽  
Response To Therapy ◽  
World Health ◽  
Peritoneal Disease ◽  
Cross Sectional ◽  
Pubmed Search

725 Background: Peritoneal metastases occur in 6-15% of patients with metastatic colorectal cancer. Non-invasive detection of peritoneal metastases is difficult given limitations in discrimination of cross sectional imaging. We hypothesized that patients with peritoneal metastases are underrepresented in clinical trials. Methods: Randomized controlled trials of systemic chemotherapy for metastatic colorectal cancer between 2003-16 were included after a PubMed search. Articles were restricted to those published in leading oncology journals and with ≥100 patients (total). Protocol designs were hand searched to identify whether clinical trials explicitly included or reported on patients with peritoneal metastases. Results: Of 72 clinical trials identified, 7 (10%) studies specifically reported inclusion of peritoneal disease (Table 1). Of 45,783 patients enrolled in all trials, 670 patients (1.5%) specifically had peritoneal metastases. Response for peritoneal disease was measured using Response Evaluation Criteria in Solid Tumors (RECIST) criteria in 6 (of 7, 86%) and modified World Health Organization (WHO) criteria in 1 but not reported in the final manuscript or supplementary material. Peritoneal specific outcomes were not reported in any study. No studies included metastatic colorectal cancer patients with peritoneal metastases alone. Conclusions: Patients with peritoneal metastases are underrepresented in published clinical trials. Specific efforts to include patients, measure burden of disease and response to therapy and report peritoneal specific outcomes are essential to draw generalizable inferences. [Table: see text]

Exceptional responses in patients with metastatic colorectal cancer enrolled in first-in-man studies from 2002 through 2012.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 687-687
Author(s):  
Shiven B. Patel ◽  
Danielle Tometich ◽  
Zachary L Reese ◽  
Sunil Sharma ◽  
Ignacio Garrido-Laguna
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Complete Response ◽  
Response To Therapy ◽  
Search Term ◽  
Tumor Type ◽  
Gamma Secretase

687 Background: Understanding exceptional responses to therapy at the molecular level may open new venues for the treatment of patients with metastatic colorectal cancer (mCRC). Responses in first-in-man (FIM) studies with targeted therapies are rare and may indicate that actionable genetic aberrations are present in these patients. Methods: We utilized Scopus using the search term “phase 1 and solid tumors” to collect all FIM studies published between 2002 and 2012. We identified patients with mCRC who attained an exceptional response to therapy defined as a complete response (CR) or a partial response (PR) lasting > 6 months (m). Results: We identified 118 FIM studies enrolling 5,369 patients with advanced malignancies. mCRC was the most common tumor type, totaling 1,055 (19.6%) patients. Of these, two patients enrolled in protocols with MDX-1106 (anti PD-1) and RG7180 (mAb EGFR) attained a complete response (CR). Five patients had PR lasting > 6 m. These patients were treated with RG7180 (time on study 7.8 m), Apatinib, a VEGFR tyrosine kinase inhibitor (8.5 and 7.1 m), PV701, a replication-competent oncolytic virus (10 m) and RO4929097, a gamma-secretase inhibitor (7 m). In addition two patients had PR lasting < 6 m with regorafenib (5.3 m) and RG7180 (5.6 m). This database of exceptional responders to therapy will be publicly available at Huntsman Cancer Institute website. Currently, regorafenib and EGFR mAbs (cetuximab and panitumumab) are approved for use in mCRC. EGFR mAbs have shown improvement in survival in RAS wild-type mCRC. Clinical trials are underway evaluating apatinib. Anti-PD1s have shown limited activity as single agents in mCRC and are currently undergoing testing in combination with chemotherapy. Conclusions: We identified exceptional responses among patients with mCRC enrolled in FIM in the last decade. Ongoing efforts are directed to conduct next generation sequencing (NGS) in archived tissue from these patients. Ultimately, this initiative may facilitate the identification of biomarkers of response to be tested in clinical trials with these or novel drugs sharing similar mechanisms of action.

Under-representation of peritoneal metastases in published clinical trials of metastatic colorectal cancer

2017 ◽  
Vol 18 (6) ◽  
pp. 711-712 ◽  
Author(s):  
Jennifer Tseng ◽  
Darren S Bryan ◽  
Elizabeth Poli ◽  
Manish Sharma ◽  
Blase N Polite ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Peritoneal Metastases

scholarly journals Impact of geography on prognostic outcomes of 21,509 patients with metastatic colorectal cancer enrolled in clinical trials: an ARCAD database analysis

2021 ◽  
Vol 13 ◽  
pp. 175883592110205
Author(s):  
Jun Yin ◽  
Shaheenah Dawood ◽  
Romain Cohen ◽  
Jeff Meyers ◽  
John Zalcberg ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Central Europe ◽  
Randomized Clinical Trials ◽  
Performance Status ◽  
The United States ◽  
World Health ◽  
Biological Therapies ◽  
The Uk

Background: Benchmarking international cancer survival differences is necessary to evaluate and improve healthcare systems. Our aim was to assess the potential regional differences in outcomes among patients with metastatic colorectal cancer (mCRC) participating in international randomized clinical trials (RCTs). Design: Countries were grouped into 11 regions according to the World Health Organization and the EUROCARE model. Meta-analyses based on individual patient data were used to synthesize data across studies and regions and to conduct comparisons for outcomes in a two-stage random-effects model after adjusting for age, sex, performance status, and time period. We used mCRC patients enrolled in the first-line RCTs from the ARCAD database, which provided enrolling country information. There were 21,509 patients in 27 RCTs included across the 11 regions. Results: Main outcomes were overall survival (OS) and progression-free survival (PFS). Compared with other regions, patients from the United Kingdom (UK) and Ireland were proportionaly over-represented, older, with higher performance status, more frequently male, and more commonly not treated with biological therapies. Cohorts from central Europe and the United States (USA) had significantly longer OS compared with those from UK and Ireland ( p = 0.0034 and p < 0.001, respectively), with median difference of 3–4 months. The survival deficits in the UK and Ireland cohorts were, at most, 15% at 1 year. No evidence of a regional disparity was observed for PFS. Among those treated without biological therapies, patients from the UK and Ireland had shorter OS than central Europe patients ( p < 0.001). Conclusions: Significant international disparities in the OS of cohorts of mCRC patients enrolled in RCTs were found. Survival of mCRC patients included in RCTs was consistently lower in the UK and Ireland regions than in central Europe, southern Europe, and the USA, potentially attributed to greater overall population representation, delayed diagnosis, and reduced availability of therapies.

A Critical Review of Second-generation anti-EGFR Monoclonal Antibodies in Metastatic Colorectal Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Daniel Sur ◽  
Andrei Havasi ◽  
Alecsandra Gorzo ◽  
Claudia Burz
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Second Generation ◽  
Current Data ◽  
Braf Mutations ◽  
Durable Response ◽  
Ongoing Research

Background: Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression and drug resistance helped develop a new generation of anti-EGFR mAbs. These second-generation mAbs have been developed to overcome existing resistance mechanisms and to limit common side effects. For the moment, existing literature suggests that these novel anti-EGFR mAbs are far from finding their way to clinical practice soon. Objective: In this review, we summarize and evaluate current data regarding ongoing research and completed clinical trials for different second-generation anti-EGFR monoclonal antibodies. Conclusion: Anti-EGFR mAbs exhibit efficacy in advanced colorectal cancer, but second-generation mAbs failed to prove their benefit in the treatment of metastatic colorectal cancer. Understanding the biological basis of primary and acquired drug resistance could allow scientists to design better clinical trials and develop improved second-generation mAbs.

scholarly journals Regorafenib in metastatic colorectal cancer: more data for clinical decisions

2021 ◽  
Vol 23 (3) ◽  
pp. 436-441
Author(s):  
Vladislav V. Petkau ◽  
Alisa A. Karimova ◽  
Zinaida V. Akishina
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Tumor Microenvironment ◽  
Metastatic Colorectal Cancer ◽  
Kinase Inhibitor ◽  
Cancer Drug ◽  
Efficacy And Safety ◽  
Tumor Immunogenicity ◽  
Metastatic Activity ◽  
Multiple Kinase Inhibitor

Regorafenib is a multiple kinase inhibitor. It influences/blocks angiogenesis (VEGFR1-3, TIE2), proliferation (KIT, RET, RAF-1, BRAF), metastatic activity (VEGFR2-3, PDGFR), tumor immunogenicity (CSF1R), tumor microenvironment (PDGFR-, PDGFR-, FGFR1-2). Regorafenib has several indications including metastatic colorectal cancer. Efficacy and safety of regorafenib data from clinical trials (CORRECT, CONCUR, CONSIGN) and observational trials from real world (REBECCA, CORRELATE, RECORA, PMS, REGOTAS) are summarized and presented in this issue. State of the matter of molecular-biologic predictors (KRAS, PIK3CA ANG-2, VEGF-A, LDH, CCL5/CCR5, CA 19-9) and radiological predictors (RadioCORRECT and other trials) is highlighted. Regimens with dose modification and its influence on effectiveness and tolerability of regorafenib are described according to the data from ReDOS, RESET, REARRANGE trials. The results from retrospective trials comparing regorafenib and another approved for refractory metastatic colorectal cancer drug trifluridine/tipiracil are presented.

scholarly journals Evaluation of Continuous Tumor-Size–Based End Points as Surrogates for Overall Survival in Randomized Clinical Trials in Metastatic Colorectal Cancer

2019 ◽  
Vol 2 (9) ◽  
pp. e1911750
Author(s):  
Tomasz Burzykowski ◽  
Elisabeth Coart ◽  
Everardo D. Saad ◽  
Qian Shi ◽  
Dirkje W. Sommeijer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Tumor Size ◽  
Randomized Clinical Trials ◽  
End Points

Phase II Trial of Chronomodulated Infusion of High-Dose Fluorouracil and l-Folinic Acid in Previously Untreated Patients With Metastatic Colorectal Cancer

2002 ◽  
Vol 20 (5) ◽  
pp. 1175-1181 ◽  
Author(s):  
H. Curé ◽  
V. Chevalier ◽  
A. Adenis ◽  
N. Tubiana-Mathieu ◽  
G. Niezgodzki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
World Health ◽  
Fixed Dose ◽  
High Dose

PURPOSE: To study tolerability and efficacy of an intensified chronomodulated schedule of fluorouracil (5-FU) and l-folinic acid (l-FA) as first-line treatment of metastatic colorectal cancer, 5-FU was given near individually determined dose-limiting toxicity in a multicenter phase II trial. PATIENTS AND METHODS: One hundred patients (68 men and 32 women, median age 62 years, World Health Organization performance status ≤ 2) with previously untreated and inoperable metastases received chronomodulated daily infusion of 5-FU/l-FA (from 10:00 pm to 10:00 am with peak at 4:00 am). 5-FU dose was escalated from 900 to 1,100 mg/m2/d with fixed dose of l-FA at 150 mg/m2/d for 4 days every 14 days. RESULTS: 5-FU dose escalation was achieved in 66% of the patients. Grade 3 to 4 toxicities mainly consisted of nausea or vomiting (14% of patients and 1.5% of courses), hand-foot syndrome (38% of patients and 8% of courses), mucositis (26% of patients and 4% of courses), and diarrhea (21% of patients and 2.3% of courses). Objective response rate (ORR) was 41% (95% confidence interval, 31.5% to 50.5%). Twenty patients underwent metastases surgery; among these, 12 had a complete resection. Median progression-free survival was 7 months. Median survival was 17 months; 28% of the patients were alive at 2 years and 18.6% at 3 years. CONCLUSION: The ORR achieved with intensified chronomodulated delivery of 5-FU/l-FA was nearly twice as high as that earlier obtained by our cooperative group using less intensive 5-FU/FA chronotherapy.

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