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Adjuvant chemotherapy for stage III colon cancer: does timing matter?

https://arctichealth.org/en/permalink/ahliterature132356
Source
Dis Colon Rectum. 2011 Sep;54(9):1082-9
Publication Type
Article
Date
Sep-2011
Author
Piotr M Czaykowski
Sharlene Gill
Hagen F Kennecke
Vallerie L Gordon
Donna Turner
Author Affiliation
Department of Medical Oncology and Hematology, CancerCare Manitoba, Winnipeg, Manitoba, Canada. Piotr.czaykowski@cancercare.mb.ca
Source
Dis Colon Rectum. 2011 Sep;54(9):1082-9
Date
Sep-2011
Language
English
Publication Type
Article
Keywords
Aged
British Columbia
Chemotherapy, Adjuvant
Chi-Square Distribution
Colonic Neoplasms - drug therapy - pathology - surgery
Female
Humans
Lymphatic Metastasis
Male
Middle Aged
Neoplasm Staging
Proportional Hazards Models
Registries
Retrospective Studies
Survival Rate
Time Factors
Treatment Outcome
Abstract
Clinical trials commonly mandate that adjuvant chemotherapy for colon cancer should commence within 8 weeks (56 days) of surgery.
We investigated the consequences of the timing of adjuvant chemotherapy for stage III colon cancer.
This is a retrospective review of all patients with newly diagnosed stage III colon cancer who received adjuvant chemotherapy in 2 provincial centers in 1999 and 2000. The impact of time to adjuvant chemotherapy on overall survival and relapse-free survival was analyzed by the use of univariate and multivariate Cox modeling, adjusting for prognostic factors.
Three hundred forty-five subjects were included. Median time to adjuvant chemotherapy was 50 days (range, 20-242 days); in 111 (32.2%) patients, it was beyond 56 days. On univariate analysis, time >56 days was nonsignificantly associated with a hazard ratio of death of 1.31 (P = .12). Similar results were seen for relapse-free survival. Planned exploratory analysis suggests that the commencement of adjuvant chemotherapy up to 10 weeks postsurgery still confers a benefit.
Delaying adjuvant chemotherapy in stage III colon cancer beyond 8 to 10 weeks postsurgery appears to be associated with diminished benefit.
PubMed ID
21825887 View in PubMed
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Adjuvant systemic chemotherapy for Stage II and III colon cancer after complete resection: an updated practice guideline.

https://arctichealth.org/en/permalink/ahliterature136254
Source
Clin Oncol (R Coll Radiol). 2011 Jun;23(5):314-22
Publication Type
Article
Date
Jun-2011
Author
D J Jonker
K. Spithoff
J. Maroun
Author Affiliation
Ottawa Hospital Regional Cancer Centre, Ottawa, Ontario, Canada. djonker@ottawahospital.on.ca
Source
Clin Oncol (R Coll Radiol). 2011 Jun;23(5):314-22
Date
Jun-2011
Language
English
Publication Type
Article
Keywords
Antineoplastic Agents - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Chemotherapy, Adjuvant
Colonic Neoplasms - drug therapy - pathology - surgery
Humans
Neoplasm Staging
Ontario
Abstract
The standard adjuvant therapy for resected stage III colon cancer has been intravenous 5-fluorouracil. However, newer chemotherapy agents, such as capecitabine, oxaliplatin and irinotecan, have been investigated in clinical trials since the publication of the original guidelines. The Gastrointestinal Cancer Disease Site Group (DSG) conducted a systematic review of the evidence for the use of adjuvant systemic chemotherapy for patients with resected stage II and III colon cancer and developed an updated practice guideline based on that evidence and expert consensus. The following research questions were addressed: Should patients with stage II or III colon cancer receive adjuvant systemic chemotherapy? What are the preferred adjuvant systemic chemotherapy options for patients with completely resected stage II or III colon cancer? Outcomes of interest were disease-free survival, overall survival, adverse effects and quality of life.
A systematic search of published studies was conducted for the time period following the publication of the original guidelines to identify relevant randomised trials and syntheses of evidence in the form of meta-analyses. Recommendations were based on that evidence, evidence contained in the original guidelines and consensus of the Gastrointestinal Cancer DSG. The systematic review and practice guideline were externally reviewed through a mailed survey of practitioners in Ontario, Canada.
Recommendations were drafted based on the available evidence and expert consensus.
The routine use of adjuvant chemotherapy for all patients with stage II colon cancer is not recommended. However, a subset of patients with high-risk stage II disease should be considered for adjuvant therapy. Patients with completely resected stage III colon cancer should be offered adjuvant chemotherapy. Treatment should depend on factors such as patient suitability and preference, and patients and clinicians must work together to determine the optimal course of treatment.
Notes
Comment In: Clin Oncol (R Coll Radiol). 2011 Jun;23(5):312-320598514
PubMed ID
21397476 View in PubMed
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[Adjuvant systemic chemotherapy in colon cancer]

https://arctichealth.org/en/permalink/ahliterature22753
Source
Ugeskr Laeger. 1996 Feb 26;158(9):1222-7
Publication Type
Article
Date
Feb-26-1996
Author
H H Raskov
Author Affiliation
Kirurgisk gastroenterologisk afdeling D, Amtssygehuset i Gentofte.
Source
Ugeskr Laeger. 1996 Feb 26;158(9):1222-7
Date
Feb-26-1996
Language
Danish
Publication Type
Article
Keywords
Adjuvants, Immunologic - administration & dosage
Antimetabolites, Antineoplastic - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Chemotherapy, Adjuvant
Colonic Neoplasms - drug therapy - mortality - surgery
English Abstract
Fluorouracil - administration & dosage
Humans
Leucovorin - administration & dosage
Levamisole - administration & dosage
Prognosis
Abstract
The prognosis for patients with cancer of the colon is dubious. An intendedly curative colon resection is performed in two-thirds of these patients, but half of them will subsequently die from metastatic disease. Randomized trials of adjuvant therapy with fluorouracil in combination with levamisole or leucovorin have shown significant benefit in terms of increased disease-free survival and overall survival. In 1990 adjuvant treatment was recommended as routine therapy in high risk patients in USA. A number of European countries are routinely treating high risk patients with Dukes' C coloncarcinoma. The recommendations are based on results from several cooperative trials reviewed in this article. Treatment related toxicity accelerates with increasing age but was acceptable in the reviewed trials. Adjuvant therapy is widely accepted as an important supplement to surgery in high risk patients. A Conference on the results and experiences now available should take place in the near future in order to establish a national consensus on adjuvant chemotherapy in Denmark. Patients with resected Dukes' C coloncarcinoma should receive adjuvant chemotherapy including 5-fluorouracil and leucovorin. Randomized trials are needed to establish the most effective regimens but "no-treatment" controls are no longer ethically acceptable.
PubMed ID
8644427 View in PubMed
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Amino-substituted 2-[2'-(dimethylamino)ethyl]-1,2-dihydro-3H- dibenz[de,h]isoquinoline-1,3-diones. Synthesis, antitumor activity, and quantitative structure--activity relationship.

https://arctichealth.org/en/permalink/ahliterature23276
Source
J Med Chem. 1995 Mar 17;38(6):983-93
Publication Type
Article
Date
Mar-17-1995
Author
S M Sami
R T Dorr
A M Sólyom
D S Alberts
W A Remers
Author Affiliation
Department of Pharmacology/Toxicology, University of Arizona, Tucson 85721.
Source
J Med Chem. 1995 Mar 17;38(6):983-93
Date
Mar-17-1995
Language
English
Publication Type
Article
Keywords
Animals
Antineoplastic Agents - chemical synthesis - pharmacology - toxicity
Cattle
Colonic Neoplasms - drug therapy
Comparative Study
DNA - metabolism
Doxorubicin - pharmacology - toxicity
Heart Diseases - chemically induced
Humans
Imides - pharmacology - toxicity
Isoquinolines - chemical synthesis - pharmacology - toxicity
Leukemia P388 - drug therapy
Male
Mice
Mice, Inbred DBA
Mitoxantrone - pharmacology - toxicity
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Structure-Activity Relationship
Tumor Cells, Cultured
Abstract
Sets of 2-[2-(dimethylamino)ethyl]-1,2-dihydro-3H- dibenz[de,h]isoquinoline-1,3-diones with amino and actylamino groups at each of the eight positions on the anthracene nucleus were synthesized from appropriately substituted anthracenes. Their evaluation in in vitro antitumor and cardiotoxicity assays revealed a very strong dependence of potency on the position of substitution. Certain compounds, including the 4-, 5-, 7-, and 9-amino derivatives, showed significantly higher potency than the unsubstituted parent compound, azonafide. Among them, 7-aminoazonafide had low cardiotoxicity relative to cytotoxicity. In general, the acetylamino analogues were less potent than the amino derivatives against tumor cells and neonatal rat heart myocytes; however, 5-(acetylamino)azonafide was highly cardiotoxic. 9-Aminoazonafide was more efficacious than azonafide or amonafide against P388 leukemia in mice. Statistically significant correlations were made between the ability of amino analogues to increase the transition melt temperature (delta Tm) of DNA and their potency against solid tumors, leukemia cells, or cardiac myocytes.
PubMed ID
7699715 View in PubMed
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Antitumor activity of carcinoma-reactive BR96-doxorubicin conjugate against human carcinomas in athymic mice and rats and syngeneic rat carcinomas in immunocompetent rats.

https://arctichealth.org/en/permalink/ahliterature21930
Source
Cancer Res. 1997 Oct 15;57(20):4530-6
Publication Type
Article
Date
Oct-15-1997
Author
H O Sjögren
M. Isaksson
D. Willner
I. Hellström
K E Hellström
P A Trail
Author Affiliation
Department of Cell and Molecular Biology, University of Lund, Sweden.
Source
Cancer Res. 1997 Oct 15;57(20):4530-6
Date
Oct-15-1997
Language
English
Publication Type
Article
Keywords
Adenocarcinoma - drug therapy - pathology - secondary
Animals
Antibodies, Monoclonal - therapeutic use
Antineoplastic Agents - therapeutic use
Colonic Neoplasms - drug therapy - pathology
Doxorubicin - therapeutic use
Female
Humans
Immunotoxins - therapeutic use
Liver Neoplasms - drug therapy - pathology - secondary
Mice
Mice, Nude
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Transplantation, Heterologous
Transplantation, Isogeneic
Tumor Cells, Cultured
Abstract
The internalizing monoclonal antibody BR96 was conjugated to the anticancer drug doxorubicin (DOX) using an acid-labile hydrazone bond to DOX and a thioether bond to the monoclonal antibody. The resulting conjugate, termed BR96-DOX, binds to a tumor-associated Lewis(y) antigen that is abundantly expressed on the surface of human carcinoma cells. BR96-DOX binds to RCA, a human colon carcinoma cell line, and BN7005, a transplantable colon carcinoma induced in a Brown Norway (BN) rat by 1,2-dimethyl-hydrazine. BR96-DOX produces cures of established s.c. RCA human colon carcinomas in athymic mice and rats. BR96-DOX also cured both s.c. and intrahepatic BN7005 tumors in immunocompetent BN rats. Unconjugated DOX, given at its maximum tolerated dose, and matching doses of nonbinding IgG-DOX conjugate were not active against RCA or BN7005 carcinomas. An anticonjugate antibody response was produced in BN rats treated with BR96-DOX. However, this could be largely prevented by administering the immunosuppressive drug deoxyspergualin. These results confirm the concept of antibody-directed therapy in models in which the targeted antigen is expressed both in normal tissues and tumors. The findings in BN7005 further demonstrate efficacy of BR96-DOX therapy in a model in which the tumor is syngeneic and the host is immunocompetent.
PubMed ID
9377565 View in PubMed
Less detail

Antitumoral and mechanistic studies of ianthelline isolated from the Arctic sponge Stryphnus fortis.

https://arctichealth.org/en/permalink/ahliterature119933
Source
Anticancer Res. 2012 Oct;32(10):4287-97
Publication Type
Article
Date
Oct-2012
Author
Kine Ã? Hanssen
Jeanette H Andersen
Trine Stiberg
Richard A Engh
Johan Svenson
Anne-Marie Genevière
Espen Hansen
Author Affiliation
Centre for Research-based Innovation on Marine Bioactivities and Drug Discovery, MabCent, University of Tromsø, Breivika, Tromsø, Norway. kine.o.hanssen@uit.no
Source
Anticancer Res. 2012 Oct;32(10):4287-97
Date
Oct-2012
Language
English
Publication Type
Article
Keywords
Animals
Antineoplastic Agents - pharmacology
Biological Products - pharmacology
Breast Neoplasms - drug therapy
Carcinoma - drug therapy
Cell Division - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Colonic Neoplasms - drug therapy
Female
Humans
Imidazoles - pharmacology
Leukemia - drug therapy
Melanoma - drug therapy
Porifera - chemistry
Protein Kinase Inhibitors - pharmacology
Sea Urchins - drug effects - embryology
Spindle Apparatus - drug effects
Tyrosine - analogs & derivatives - pharmacology
Abstract
Ianthelline was isolated from the Arctic sponge Stryphnus fortis. The structure of the compound has been previously described. However, only limited bioactivity data are available and little has been reported about the cytotoxic potential of ianthelline since its discovery. In addition, no study has so far aimed at identifying which cellular mechanisms are affected by ianthelline to generate cytotoxicity.
The cytotoxicity of ianthelline was tested against one non-malignant and ten malignant cell lines. The effects of ianthelline on key cell division events were studied in sea urchin embryos. Tyrosine kinase ABL (ABL), cAMP-dependent protein kinase A (PKA), protein-tyrosine phosphatase 1B (PTP1B), and a panel of 131 kinases were further tested for sensitivity to ianthelline.
Ianthelline inhibits cellular growth in a dose- and time-dependent manner. Disturbed mitotic spindle formation was found in sea urchin embryos exposed to ianthelline. In addition, pronuclear migration and cytokinesis were severely inhibited. No effect on DNA synthesis was detectable. Ianthelline did not significantly inhibit ABL, but did provoke weak dose-dependent inhibition of PKA and PTP1B. It strongly inhibited the activity of 1 out of 131 tested kinases (to residual activity
PubMed ID
23060549 View in PubMed
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Association between receipt and timing of adjuvant chemotherapy and survival for patients with stage III colon cancer in Alberta, Canada.

https://arctichealth.org/en/permalink/ahliterature137078
Source
Cancer. 2011 Aug 15;117(16):3833-40
Publication Type
Article
Date
Aug-15-2011
Author
Isac S F Lima
Yutaka Yasui
Andrew Scarfe
Marcy Winget
Author Affiliation
School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
Source
Cancer. 2011 Aug 15;117(16):3833-40
Date
Aug-15-2011
Language
English
Publication Type
Article
Keywords
Adenocarcinoma - drug therapy - mortality
Aged
Alberta
Antineoplastic Agents - administration & dosage
Chemotherapy, Adjuvant
Colonic Neoplasms - drug therapy - mortality
Humans
Time Factors
Abstract
Surgery followed by adjuvant chemotherapy has been standard treatment for stage III colon cancer since 1990. However, to date, clinical trials have not been conducted to determine the definitive outer time limit by which adjuvant chemotherapy should be received for optimal survival benefit. The objective of the current study was to assess the association between the receipt/timing of adjuvant chemotherapy and patient survival in clinical practice.
Residents of Alberta who were diagnosed with stage III colon adenocarcinoma in years 2000 to 2005 who underwent surgery were included in the study. Patients were identified from the Alberta Cancer Registry and were linked to hospital data and neighborhood-level socioeconomic data from the 2001 Canadian Census. Cox proportional hazards models were used to estimate hazard ratios of death according to the timing of chemotherapy.
There were 1053 patients in the study; 648 (61%) initiated adjuvant chemotherapy within 16 weeks of surgery. There was no difference in overall survival or colon cancer-specific survival between those who received adjuvant chemotherapy from 8 to 12 weeks postsurgery compared with those who received it within 8 weeks. However, those who received chemotherapy 12 to 16 weeks after surgery and those who either received it >16 weeks after surgery or received no treatment had a 43% and 107% greater risk of dying, respectively, than those who received chemotherapy within 8 weeks of surgery (hazard ratio, 1.43 [95% confidence interval, 0.96-2.13] and hazard ratio, 2.07 [95% confidence interval, 1.56-2.76], respectively). Analyses were controlled for age, year, and region of residence at diagnosis; sex; neighborhood-level socioeconomic factors; and number of comorbidities.
The results from this study were consistent with current guideline recommendations in Alberta that patients with stage III adenocarcinoma should receive chemotherapy within 12 weeks of surgery.
PubMed ID
21319156 View in PubMed
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Capecitabine as third line therapy in patients with advanced colorectal cancer.

https://arctichealth.org/en/permalink/ahliterature16849
Source
Acta Oncol. 2005;44(3):236-9
Publication Type
Article
Date
2005
Author
Michael Gubanski
Gisela Naucler
Agneta Almerud
Anders Lideståhl
Pehr A R M Lind
Author Affiliation
Department of Oncology, Karolinska University Hospital-Huddinge, Stockholm, Sweden. gubanski@kus.se
Source
Acta Oncol. 2005;44(3):236-9
Date
2005
Language
English
Publication Type
Article
Keywords
Adult
Aged
Antimetabolites, Antineoplastic - administration & dosage - therapeutic use
Antineoplastic Agents - administration & dosage
Antineoplastic Agents, Phytogenic - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Camptothecin - administration & dosage - analogs & derivatives
Carcinoembryonic Antigen - analysis
Colonic Neoplasms - drug therapy
Deoxycytidine - analogs & derivatives - therapeutic use
Disease Progression
Drug Resistance, Neoplasm
Female
Fluorouracil - administration & dosage
Humans
Male
Middle Aged
Organoplatinum Compounds - administration & dosage
Palliative Care
Prodrugs - administration & dosage - therapeutic use
Rectal Neoplasms - drug therapy
Retrospective Studies
Survival Rate
Tumor Markers, Biological - analysis
Abstract
This study sought to determine whether third line therapy with capecitabine (cap.) could provide any clinical benefit in patients with advanced colorectal cancer who have progressed on 5-Fu combination therapy with both irinotecan and oxaliplatin. Twenty patients who were pretreated with and had progressed on irinotecan+Nordic FLv (5-Fu/leukovorin) and oxaliplatin+c.i. 5-Fu/leukovorin were studied. Cap. was administered at 1000-1250 mg/m2 bid d1-14 q 3 w. Time to progression (TTP) (either radiological or clinical) and overall survival (OS) were estimated with the Kaplan-Meier actuarial method. The median number of administered cap. courses was four. No radiological or biochemical responses were observed. Three patients were classified as having stable disease at three months. Two of these patients had, however, minor radiological progression and a =100% increase in CEA compared to base line. Seventeen patients were classified as having progressive disease during the first three months period. Median TTP and OS were 2.8 months and 6.1 months, respectively. A response rate of =15% for third line cap. in metastatic CRC can be ruled out. Median PFS was limited in the study population. This observation and the few cases with SD at three months, lead us to believe that little or no clinical benefit can be expected from single drug cap. in patients with irinotecan- and oxaliplatin-combination resistant advanced colorectal cancer.
PubMed ID
16076695 View in PubMed
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36 records – page 1 of 4.