Surrogate endpoints in assessment of new drugs in colorectal cancer

The Lancet ◽  
2000 ◽  
Vol 356 (9227) ◽  
pp. 353-354 ◽  
Author(s):  
David P Kelsen
Keyword(s):  
Colorectal Cancer ◽  
New Drugs ◽  
Surrogate Endpoints

scholarly journals sFLT-1 inhibits proliferation, migration, and invasion of colorectal cancer SW480 cells through vascular mimicry formation suppression

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769833 ◽  
Author(s):  
Wang Jinjun ◽  
Wang Zhaowei ◽  
Li Qiang ◽  
Xue Zhijun ◽  
Zhang Juanzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tyrosine Kinase ◽  
Three Dimensional ◽  
New Drugs ◽  
Migration And Invasion ◽  
Vascular Endothelial ◽  
Three Dimensional Model ◽  
Vascular Endothelial Cadherin ◽  
Sw480 Cells ◽  
Vascular Mimicry

To investigate the effects of soluble fms-like tyrosine kinase-1 on the vascular mimicry formation, proliferation, migration, and invasion of colorectal cancer SW480 cells. The recombinant plasmid pBLAST49-sFLT-1 or pBLAST49 control plasmid was transfected into SW480 cells to obtain hsFLT-1-SW480 or Ctrl-SW480 cells. The three-dimensional model culture, sulforhodamine B assay, scratch assay, and Transwell assay were performed to detect the vascular mimicry formation, proliferation, migration, and invasion of colorectal cancer SW480 cells, respectively. Western blotting was used to detect the expression of vascular endothelial–cadherin protein. Compared with Ctrl-SW480 cells, vascular mimicry formation ((0.85 ± 0.04) vs (7.40 ± 0.69), p < 0.05) and vascular endothelial–cadherin expression ((1.25 ± 0.08) vs (1.89 ± 0.03), p < 0.05) were significantly decreased, and the growth rate was also significantly decreased in hsFLT-1-SW480 cells ((32.54 ± 5.12) vs (88.13 ± 11.52), p < 0.05). Moreover, the migration ((0.46 ± 0.08) vs (0.94 ± 0.03), p < 0.05) and invasion capacity ((59.14 ± 3.64) vs (134.85 ± 10.16), p < 0.05) of SW480 cells were significantly inhibited upon soluble fms-like tyrosine kinase-1 transfection. soluble fms-like tyrosine kinase-1 inhibits cell proliferation, migration, and invasion of colorectal cancer SW480 cells through suppression of vascular mimicry formation, which provides a good basis for the development of new drugs for the treatment of colorectal cancer by targeting both angiogenesis and vascular mimicry formation.

scholarly journals Adjuvant treatment of colorectal cancer

2002 ◽  
Vol 49 (2) ◽  
pp. 15-18
Author(s):  
J.A. Wils
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Treatment ◽  
Large Scale ◽  
New Drugs ◽  
Morbidity And Mortality ◽  
The Past ◽  
The Future ◽  
The Usa

Colorectal cancer is a leading cause of morbidity and mortality, with approximately 300,000 new cases and 200,000 related deaths in Europe and the USA each year. Adjuvant treatment of colorectal cancer is now widely accepted and can reduce mortality with approximately 10%. This can be considered as one of the major achievements in oncology from the past decade. Current results will be discussed and strategies for the future will be outlined, including on-going or planned large-scale trials with new drugs and approaches.

scholarly journals Trends in the costs of drugs launched in the UK between 1981 and 2015: an analysis of the launch price of drugs in five disease areas

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e027625 ◽  
Author(s):  
Derek J Ward ◽  
Lucy Doos ◽  
Andrew Stevens
Keyword(s):  
Colorectal Cancer ◽  
Cross Sectional Study ◽  
New Drugs ◽  
Regulatory Agencies ◽  
European Medicines Agency ◽  
Biological Drugs ◽  
Cross Sectional ◽  
Medical Benefits ◽  
Using Data ◽  
The Uk

ObjectivesTo investigate the trend in the launch price of new drugs for five common health conditions.DesignCross-sectional study using data on new drugs launched in the UK between 1981 and 2015 for hypertension, asthma, rheumatoid arthritis, schizophrenia and colorectal cancer.Data and sourcesAll drugs marketed in the UK between 1981 and 2015 (inclusive), and licensed specifically for the treatment of one of the five chosen conditions were included in the study. Newly launched medicines and their launch prices were identified by hand-searching all editions of the British National Formulary in addition to searching the websites of relevant regulatory agencies (European Medicines Agency and Medicines and Healthcare products Regulatory Agency). The launch price in UK pounds for a 28-day supply of each medicine at a typical or usual maintenance dose was adjusted for the effects of general inflation using the gross domestic product deflator series.Results104 drugs were included in our study with a mean inflation-adjusted 28-day launch price of £288 (SD £678). The launch price of new drugs varied significantly across the five conditions, with drugs for hypertension having the lowest mean price (£27) and drugs for colorectal cancer having the highest mean price (£1590) (p<0.001). There were large increases in launch prices across the study period, but the magnitude and pattern was markedly different between therapeutic areas. Biological drugs represented 13.5% of all included drugs and had a significantly higher launch price than non- biological drugs (£1233 vs £141, p<0.001). 22.1% of included drugs were first-of-kind and had a significantly higher launch price than follow-on drugs (£768 vs £151) (p<0.0001).ConclusionDrugs prices continue to increase across different therapeutic areas. This has some association with novelty, but, it is not clear if this increase in price is associated with medical benefits.

Treatment of Advanced Colorectal Cancer (CRC) in Daily Practice: Results of a Survey in two Italian Regions, Piemonte and Valle D'aosta

1998 ◽  
Vol 84 (5) ◽  
pp. 562-566 ◽  
Author(s):  
Alessandro Comandone ◽  
Roberto Berardo ◽  
Roberto Faggiuolo ◽  
Antonella Boglione ◽  
Paola Bergnolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Performance Status ◽  
Daily Practice ◽  
New Drugs ◽  
Therapeutic Choice ◽  
Italian Regions ◽  
Important Health ◽  
Definition Of ◽  
No Gold Standard

Aims and background Colorectal cancer (CRC) is one of the most important health problems in Western countries: it is the fourth cancer in terms of incidence and the second cause of cancer death. Surgery is the main therapeutic choice and there is broad consensus on the role of adjuvant chemotherapy (CT) after resection. Unfortunately, 50% of the patients will relapse and die of the disease. Palliative CT based on 5-fluorouracil (5FU) may induce a 9-48% response rate with a median survival of 11.5 months. At present there is no gold standard for CT in advanced CRC and the situation has become more complicated since the advent of new drugs (Raltitrexed, Irinotecan, Oxaliplatin). The aim of this study was the identification of the different approaches to treatment of advanced CRC among the clinicians (oncologists, radiologists, internal medicine specialists, surgeons) who practice CT. Methods and study design Forty-six clinicians from two Italian Regions (Piemonte and Valle d'Aosta) were interviewed by telephone. Results 5FU modulated with Lederfolin according to the classic Machover scheme is the main option in daily practice. More sophisticated therapies are reserved to patients with a good performance status (PS) and are prescribed only in the larger centers. The planned therapies usually consist of six courses. Restaging may be performed after three or six courses. A marked difference has been recorded in the evaluation of a situation of no change (NC): 25.5% of the clinicians evaluate stable disease as a positive result. In the event of disease progression or relapse, 35% of the clinicians do not prescribe second-line CT. In case of further treatment, the options are totally subjective. Conclusions A national survey on this issue is necessary under the auspices of AIOM (Associazione Italiana Oncologia Medica) and involving oncologists, epidemiologists and statisticians, in order to define the reasons for variations in therapy in advanced CRC and determine the differences between clinicians of different age, specialization and location. This survey could lead to a definition of guidelines for the treatment of advanced CRC.

scholarly journals Targeting Colorectal Cancer Stem Cells as an Effective Treatment for Colorectal Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303381989226
Author(s):  
Yu-Shui Ma ◽  
Wen Li ◽  
Yu Liu ◽  
Yi Shi ◽  
Qin-Lu Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Human Life ◽  
Research Direction ◽  
Current Treatment ◽  
New Drugs ◽  
Colorectal Cancer Stem Cells ◽  
Cancer Tissues

As one of the common cancers that threaten human life, the recurrence and metastasis of colorectal cancer seriously affect the prognosis of patients. Although new drugs and comprehensive treatments have been adopted, the current treatment effect on this tumor, especially in advanced colorectal cancer, is still not satisfactory. More and more evidence shows that tumors are likely to be a stem cell disease. In recent years, the rise of cancer stem cell theory has provided a new way for cancer treatment. Studies have found that a small number of special cells in colorectal cancer tissues that induce tumorigenesis, proliferation, and promote tumor migration and metastasis, namely, colorectal cancer stem cells. Colorectal cancer stem cells are defined with a group of cell-surface markers, such as CD44, CD133, CD24, epithelial cell adhesion factor molecule, LGR5, and acetaldehyde dehydrogenase. They are highly tumorigenic, aggressive, and chemoresistant and thus are critical in the metastasis and recurrence of colorectal cancer. Therefore, targeting colorectal cancer stem cells may become an important research direction for the future cure of colorectal cancer.

Biologic Agents in the Treatment of Colorectal Cancer: The Last Decade; the Lost Decade?

2013 ◽  
pp. e121-e125
Author(s):  
Alan P. Venook ◽  
Leonard B. Saltz
Keyword(s):  
Colorectal Cancer ◽  
Biologic Agents ◽  
New Drugs ◽  
Adjuvant Setting ◽  
Cure Rate ◽  
New Agents ◽  
Metastatic Setting ◽  
Key Points ◽  
Lost Decade

KEY POINTS After almost 40 years of minimal progress, the period from 1996 to 2003 saw a flurry of new drugs become available. Progress since 2003 has been minimal. Most new agents with activity in the metastatic setting (irinotecan, bevacizumab, cetuximab) do not have activity in the adjuvant setting and so have not increased the cure rate. Combinations of biologics have been disappointing. Progress to date is less than we would have expected. Therapy individualized according to molecular characterization of each tumor appears to be the way forward.

Double KRAS and BRAF mutations in colorectal cancer in a single oncologic department series.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14657-e14657 ◽  
Author(s):  
Pamela Francesca Guglielmini ◽  
Maura Rossi ◽  
Federica Grosso ◽  
Sara Orecchia ◽  
Marco Galliano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Disease ◽  
Point Mutations ◽  
Disease Patient ◽  
Lung Lesion ◽  
New Drugs ◽  
Braf V600e ◽  
Dot Blot ◽  
Braf Mutations ◽  
Laser Medicine

e14657 Background: KRAS and BRAF mutations have prognostic and predictive value in colorectal cancer and are predominantly mutually exclusive. Only a few cases of double mutations (DM) have been reported so far but the actual incidence and presumed role in worsening prognosis is still unknown. Here we report on a series of KRAS and BRAF mutations, focusing on three cases of KRAS and BRAF DM. Methods: since May 2010, 316 consecutive colorectal cancer samples were collected by our Oncology Department; ten patients (3%) had high risk localized disease and 306 (97%) metastatic disease. Genome DNA from formalin-fixed paraffin embedded samples with tumor cells > 50% was analyzed by reverse dot blot with KRAS-BRAF StripAssay kit (Nuclear Laser Medicine). Results: KRAS point mutations were found in 141 patients (44.6%): 32% G12V, 30.5% G12D, 14.9% G13D, 6.4% G12S, 5.7% G12C, 4.9% G12A, 4.9% G12R, 0.7% G13C; V600E BRAF point mutation was found in 21 patients (6.6%). Three patients (1%) displayed DM: 2 KRAS G13D + BRAF V600E (A and B) and 1 KRAS G12V + BRAF V600E (C). Patients A and C, both aged 59, presented with metastatic disease. Patient A had a rectal primary, a single lung lesion and mediastinal nodes. He failed first line FOLFOX4 plus bevacizumab and underwent salvage surgery both on primary and metastatic disease. He relapsed in 3 months with liver and brain metastasis and died after one year from diagnosis. Patient B had huge liver lesions at presentation. She progressed after 3 courses of FOLFIRI and died after 6 months from diagnosis. Patient C was operated on for a right colon cancer, G3, pT2N2, stage IIIB with lymph vascular invasion and had adjuvant FOLFOX 4. The 6-month assessment did not show relapse. Conclusions: in our series KRAS mutation incidence was in line with literature, but G12V was far more frequent. KRAS-BRAF DM accounted for 1% of all cases and the 2 patients with metastatic disease had an aggressive course with a much lower than expected survival. To our knowledge no series of DM have been described, hindering the understanding of their biological meaning. According to our experience, metastatic double mutated patients do not respond to standard therapy and should be treated with new drugs combinations in clinical trials.

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