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2.
BMJ ; 351: h4970, 2015 Oct 06.
Article in English | MEDLINE | ID: mdl-26442928

ABSTRACT

OBJECTIVE: To examine changes in colorectal cancer mortality in 34 European countries between 1970 and 2011. DESIGN: Retrospective trend analysis. DATA SOURCE: World Health Organization mortality database. POPULATION: Deaths from colorectal cancer between 1970 and 2011. Profound changes in screening and treatment efficiency took place after 1988; therefore, particular attention was paid to the evolution of colorectal cancer mortality in the subsequent period. MAIN OUTCOMES MEASURES: Time trends in rates of colorectal cancer mortality, using joinpoint regression analysis. Rates were age adjusted using the standard European population. RESULTS: From 1989 to 2011, colorectal cancer mortality increased by a median of 6.0% for men and decreased by a median of 14.7% for women in the 34 European countries. Reductions in colorectal cancer mortality of more than 25% in men and 30% in women occurred in Austria, Switzerland, Germany, the United Kingdom, Belgium, the Czech Republic, Luxembourg, and Ireland. By contrast, mortality rates fell by less than 17% in the Netherlands and Sweden for both sexes. Over the same period, smaller or no declines occurred in most central European countries. Substantial mortality increases occurred in Croatia, the former Yugoslav republic of Macedonia, and Romania for both sexes and in most eastern European countries for men. In countries with decreasing mortality, reductions were more important for women of all ages and men younger than 65 years. In the 27 European Union member states, colorectal cancer mortality fell by 13.0% in men and 27.0% in women, compared with corresponding reductions of 39.8% and 38.8% in the United States. CONCLUSION: Over the past 40 years, there has been considerable disparity in the level of colorectal cancer mortality between European countries, as well as between men and women and age categories. Countries with the largest reductions in colorectal cancer mortality are characterised by better accessibility to screening services, especially endoscopic screening, and specialised care.


Subject(s)
Colorectal Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Databases, Factual , Europe/epidemiology , Female , Humans , Male , Middle Aged , Mortality/trends , Retrospective Studies , World Health Organization
3.
J Natl Cancer Inst ; 105(21): 1667-70, 2013 Nov 06.
Article in English | MEDLINE | ID: mdl-24108811

ABSTRACT

The traditional endpoint for assessing efficacy of chemotherapies for advanced/recurrent gastric cancer is overall survival (OS), but OS requires prolonged follow-up. We investigated whether progression-free survival (PFS) is a valid surrogate for OS. Using individual patient data from the GASTRIC meta-analysis, surrogacy of PFS was assessed through the correlation between the endpoints and through the correlation between the treatment effects on the endpoints. External validation of the prediction based on PFS was also evaluated. Individual data from 4069 patients in 20 randomized trials were analyzed. The rank correlation coefficient between PFS and OS was 0.853 (95% confidence interval [CI] = 0.852 to 0.854). The R (2) between treatment effects on PFS and on OS was 0.61 (95% CI = 0.04 to 1.00). Treatment effects on PFS and on OS were only moderately correlated, and we could not confirm the validity of PFS as a surrogate endpoint for OS in advanced/recurrent gastric cancer.


Subject(s)
Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/therapy , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Biomarkers , Disease-Free Survival , Humans , Odds Ratio , Predictive Value of Tests , Randomized Controlled Trials as Topic , Stomach Neoplasms/pathology , Treatment Outcome
4.
J Natl Cancer Inst ; 105(21): 1600-7, 2013 Nov 06.
Article in English | MEDLINE | ID: mdl-24108812

ABSTRACT

BACKGROUND: In investigations of the effectiveness of surgery and adjuvant chemotherapy for gastric cancers, overall survival (OS) is considered the gold standard endpoint. However, the disadvantage of using OS as the endpoint is that it requires an extended follow-up period. We sought to investigate whether disease-free survival (DFS) is a valid surrogate for OS in trials of adjuvant chemotherapy for gastric cancer. METHODS: The GASTRIC group initiated a meta-analysis of individual patient data collected in randomized clinical trials comparing adjuvant chemotherapy vs surgery alone for patients with curatively resected gastric cancer. Surrogacy of DFS was assessed through the correlation between the endpoints as well as through the correlation between the treatment effects on the endpoints. External validation of the prediction based on DFS was also evaluated. RESULTS: Individual patient data from 14 randomized clinical trials that included a total of 3288 patients were analyzed. The rank correlation coefficient between DFS and OS was 0.974 (95% confidence interval [CI] = 0.971 to 0.976). The coefficient of determination between the treatment effects on DFS and on OS was as high as 0.964 (95% CI = 0.926 to 1.000), and the surrogate threshold effect based on adjusted regression analysis was 0.92. In external validation, the six hazard ratios for OS predicted according to DFS were in very good agreement with those actually observed for OS. CONCLUSIONS: DFS is an acceptable surrogate for OS in trials of cytotoxic agents for gastric cancer in the adjuvant setting.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gastrectomy , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Chemotherapy, Adjuvant , Cost-Benefit Analysis , Disease-Free Survival , Drug Administration Schedule , Humans , Kaplan-Meier Estimate , Linear Models , Odds Ratio , Randomized Controlled Trials as Topic/economics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Time Factors , Treatment Outcome
5.
Eur J Cancer ; 49(7): 1565-77, 2013 May.
Article in English | MEDLINE | ID: mdl-23352439

ABSTRACT

We conducted an individual-patient-data meta-analysis of the efficacy of chemotherapy on overall survival (OS) and progression-free survival (PFS) in advanced/recurrent gastric cancer (AGC). Our primary research question was whether the experimental arms of the trials included in the meta-analysis showed a benefit as compared with their corresponding control arms. MEDLINE (up to 2010), Cochrane Central Register of Controlled Trials, National Institutes of Health (NIH) trial registry and proceedings of major oncologic and gastrointestinal cancer meetings were searched. Randomised controlled trials for AGC closed to patient accrual before the end of 2006 were eligible. As of December 2010, individual patient data were available from 22 trials (4245 patients, representing 47% of the targeted data) of 55 eligible trials. The overall comparison of experimental arms with the corresponding control arms showed statistically significant differences in terms of both OS and PFS. Hazard ratio was 0.88 (95% confidence interval 0.82-0.94, P<0.0001) for OS and 0.81 (0.76-0.88, P<0.0001) for PFS. The results of the sub-analysis of adding a given chemotherapeutic agent to any chemotherapy confirm the results of the overall analysis, with a hazard reduction of 11% for OS (P<0.01) and 26% for PFS (P<0.0001). This meta-analysis of individual patient data shows that the additions of experimental chemotherapeutic agents to pre-existing control or standard regimens have produced a modest improvement in OS and PFS. Median survival remained below 1 year for all investigated chemotherapy regimens and none emerged as a clear standard.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Disease-Free Survival , Humans , Neoplasm Recurrence, Local , Randomized Controlled Trials as Topic , Stomach Neoplasms/pathology , Treatment Outcome
6.
Int J Gynecol Cancer ; 21(1): 35-43, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21330829

ABSTRACT

PURPOSE: Accurate preoperative clinical assessment of adnexal masses can optimize outcomes by ensuring appropriate and timely surgery. This article addresses whether a new technology, ovarian HistoScanning, has an additional diagnostic value in mathematical models developed for the differential diagnosis of adnexal masses. PATIENTS AND METHODS: Transvaginal sonography-based morphological variables were obtained through blinded analysis of archived images in 199 women enrolled in a prospective study to assess the performance of ovarian HistoScanning. Logistic regression (LR) and neural network (NN) models including these variables and clinical and patient data along with the HistoScanning score (HSS) (range, 0-125; based on mathematical algorithms) were developed in a learning set (60% patients). The remaining 40% patients (evaluation set) were used to assess model performance. RESULTS: Of all morphological and clinical variables tested, serum CA-125, presence of a solid component, and HSS were most significant and used to develop the LR model. The NN model included all variables. The novel variable, HSS, offered significant improvement in the LR and NN models' performance. The LR and NN models in an independent evaluation set were found to have area under the receiver operating characteristic curve = 0.97 (95% confidence interval [CI], 94-99) and 0.93 (95% CI, 88-98), sensitivities = 83% (95% CI, 71%-91%) and 80% (95% CI, 67%-89%), and specificities = 98% (95% CI, 89%-99%) and 86% (95% CI, 72%-95%), respectively. In addition, these models showed an improved performance when compared with 3 other existing models (all P < 0.05). CONCLUSIONS: This initial report shows a clear benefit of including ovarian HistoScanning into mathematical models used for discriminating benign from malignant ovarian masses. These models may be specifically helpful to the less experienced examiner. Future research should assess performance of these models in prospective clinical trials in different populations.


Subject(s)
Image Interpretation, Computer-Assisted/methods , Neural Networks, Computer , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/pathology , Aged , CA-125 Antigen/blood , Female , Humans , Logistic Models , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prospective Studies , ROC Curve , Single-Blind Method , Ultrasonography
7.
Eur Radiol ; 20(8): 1822-30, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20306081

ABSTRACT

OBJECTIVES: To prospectively assess an innovative computer-aided diagnostic technology that quantifies characteristic features of backscattered ultrasound and theoretically allows transvaginal sonography (TVS) to discriminate benign from malignant adnexal masses. METHODS: Women (n = 264) scheduled for surgical removal of at least one ovary in five centres were included. Preoperative three-dimensional (3D)-TVS was performed and the voxel data were analysed by the new technology. The findings at 3D-TVS, serum CA125 levels and the TVS-based diagnosis were compared with histology. Cancer was deemed present when invasive or borderline cancerous processes were observed histologically. RESULTS: Among 375 removed ovaries, 141 cancers (83 adenocarcinomas, 24 borderline, 16 cases of carcinomatosis, nine of metastases and nine others) and 234 non-cancerous ovaries (107 normal, 127 benign tumours) were histologically diagnosed. The new computer-aided technology correctly identified 138/141 malignant lesions and 206/234 non-malignant tissues (98% sensitivity, 88% specificity). There were no false-negative results among the 47 FIGO stage I/II ovarian lesions. Standard TVS and CA125 had sensitivities/specificities of 94%/66% and 89%/75%, respectively. Combining standard TVS and the new technology in parallel significantly improved TVS specificity from 66% to 92% (p < 0.0001). CONCLUSIONS: Computer-aided quantification of backscattered ultrasound is a highly sensitive for the diagnosis of malignant ovarian masses.


Subject(s)
Algorithms , Image Interpretation, Computer-Assisted/methods , Ovarian Neoplasms/diagnostic imaging , Pattern Recognition, Automated/methods , Software Validation , Software , Ultrasonography, Doppler/methods , Adolescent , Adult , Aged , Aged, 80 and over , Artificial Intelligence , Europe , Female , Humans , Image Enhancement/methods , Imaging, Three-Dimensional/methods , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Young Adult
8.
J Clin Oncol ; 26(30): 4906-11, 2008 Oct 20.
Article in English | MEDLINE | ID: mdl-18794541

ABSTRACT

PURPOSE: Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials. PATIENTS AND METHODS: After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m(2) administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m(2) [FFCD] x 5 days or FU 370 mg/m(2) plus l-leucovorin 100 mg/m(2) IV x 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm). RESULTS: A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis. CONCLUSION: This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus-based regimen after complete resection of colorectal cancer metastases.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Adult , Aged , Chemotherapy, Adjuvant , Colorectal Neoplasms/mortality , Disease-Free Survival , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Liver Neoplasms/surgery , Lung Neoplasms/surgery , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Survival Rate
9.
BJU Int ; 102(11): 1560-5, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18710457

ABSTRACT

OBJECTIVE: To determine the extent to which computer-aided ultrasonography of the prostate (HistoScanning, Advanced Medical Diagnostics, Waterloo, Belgium) can identify tumour foci that correspond to a volume of >or=0.50 mL. PATIENTS AND METHODS: Between September 2004 and February 2006, 29 men were HistoScanned before scheduled radical prostatectomy. The three-dimensional raw (grey-scaled) data required for HistoScanning analysis were acquired by transrectal ultrasonography, and analysed using organ-specific tissue-characterization algorithms which form the core of the HistoScanning technology. The HistoScanning analysis results were compared with the histology of the whole-mounted prostate, step-sectioned sagittally at 5-mm intervals, and each slide analysed by 5 x 5 mm grid analysis. RESULTS: Of 29 patients, 13 had histology unknown to those evaluating the HistoScanning data. With 0.50 mL as the lower threshold for delineating and visualizing cancer volume, HistoScanning correctly predicted the presence of all 12 lesions that were subsequently confirmed to occupy >or=0.50 mL. In addition three lesions were predicted as being present and of >or=0.50 mL. These three lesions were subsequently confirmed to be present but were or=0.50 mL; these encouraging results will need to be verified in a larger group of patients.


Subject(s)
Image Interpretation, Computer-Assisted/standards , Prostate/diagnostic imaging , Prostatic Neoplasms/diagnostic imaging , Humans , Male , Prostate/pathology , Risk Assessment , Sensitivity and Specificity , Ultrasonography
10.
BJU Int ; 101(3): 293-8, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17922870

ABSTRACT

OBJECTIVE: To assess the extent to which prostate HistoScanning (PHS), a new ultrasound-based technology that uses computer-aided analysis to quantify tissue disorganization induced by malignant processes, can identify and characterize foci of prostate cancer compared with step-sectioned radical prostatectomy (RP) specimens. PATIENTS AND METHODS: Between September 2004 and February 2006, 29 men had PHS before their scheduled RP. A three-dimensional ultrasound raw-data file was acquired, and PHS analysed regions of interest (ROI) corresponding to tissue volumes of approximately 0.04 mL. In 13 men the histology was examined on sections of the whole-mount prostate onto which a grid of 5 x 5 mm squares was applied. On a test set of 14 of the 29 patients, PHS analysis was used before knowing the histology results (blinded data), to predict the maximum tumour diameter, focality, laterality and extraprostatic extension (EPE). RESULTS: Identification and characterization by PHS of the index tumour in the 14 patients in the test set correlated closely (r = 0.95, P < 0.001) with the reference test. The concordance in the attribution of multifocality (present/absent), unilateral/bilateral disease between PHS and histology was 100%. EPE as determined by PHS was attributed to all three pT3a pathological specimens in the blinded paired data. In the same set of data, EPE was attributed to one prostate cancer that on pathological inspection was deemed to be organ-confined (pT2b). CONCLUSIONS: PHS has the potential to identify and characterize prostate cancer foci noninvasively. The precision appears to be sufficient to suggest that PHS might be useful as a triage test for men deemed to be at risk of prostate cancer and who wish to avoid prostate biopsy.


Subject(s)
Image Interpretation, Computer-Assisted/standards , Prostate-Specific Antigen/blood , Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Aged , Biopsy, Needle , Cohort Studies , Humans , Image Interpretation, Computer-Assisted/methods , Male , Middle Aged , Pilot Projects , Risk Factors , Ultrasonography
11.
J Clin Oncol ; 25(14): 1891-7, 2007 May 10.
Article in English | MEDLINE | ID: mdl-17488988

ABSTRACT

Colorectal cancer (CRC) is predominantly a disease of older persons, and our population is aging. Physicians and their older patients commonly face the dilemma of whether or not to give/receive systemic chemotherapy for CRC. Evidence supports the safety and efficacy of systemic chemotherapy in fit older patients motivated enough to enroll onto clinical trials. Conversely, frail older patients are more likely to suffer adverse outcomes when faced with stressors and may not benefit from chemotherapy. However, the majority of patients are neither fit nor frail, and current evidence is insufficient to either quantify or qualify the benefit of chemotherapy for this intermediate group of patients. Thus, treatment decisions must be individualized based on each older person's physical state (eg, their function and degree of comorbidity) and values. Despite a growing body of data, a great deal of work is still needed to establish optimal strategies to care for patients diagnosed with cancer later in life.


Subject(s)
Aged , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Patient Selection , Antineoplastic Agents/adverse effects , Clinical Trials as Topic , Combined Modality Therapy , Geriatric Assessment , Humans
13.
J Clin Oncol ; 24(25): 4085-91, 2006 Sep 01.
Article in English | MEDLINE | ID: mdl-16943526

ABSTRACT

PURPOSE: Oxaliplatin, fluorouracil, and leucovorin are commonly used to treat advanced and resected colorectal cancer. This analysis compares the safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly (FOLFOX4) in patients age younger than and at least 70 years. PATIENTS AND METHODS: This retrospective analysis included 3,742 colorectal cancer patients (614 age > or = 70) from four clinical trials testing FOLFOX4 in the adjuvant, first-, and second-line settings. End points included grade > or = 3 adverse events, response rate (in advanced disease), progression or relapse-free survival, dose-intensity, and overall survival in the studies with mature survival data. RESULTS: Grade > or = 3 hematologic toxicity (neutropenia [43% v 49%; P = .04] and thrombocytopenia [2% v 5%; P = .04]) were significantly higher in older patients. Older age was not associated with increased rates of severe neurologic adverse events, diarrhea, nausea/vomiting, infection, overall incidence of grade > or = 3 toxicity (63% v 67%; P = .15), or 60-day mortality (1.1% v 2.3%; P = .20). The relative benefit of FOLFOX4 versus control did not differ by age for response rate, progression or recurrence free-survival (hazard ratio, 0.70 for FOLFOX4 v control for age < 70, 0.65 for age > or = 70; P = .42), or overall survival (hazard ratio, 0.77 age < 70, 0.82 age > or = 70; P = .79). Dose-intensity did not differ by age at cycles 1, 3, 6, or 12. CONCLUSION: FOLFOX4 maintains its efficacy and safety ratio in selected elderly patients with colorectal cancer. Its judicious use should be considered without regard to patient age, although scant data are available among patients older than 80 years.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Age Factors , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Controlled Clinical Trials as Topic , Disease-Free Survival , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Irinotecan , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Multicenter Studies as Topic , Odds Ratio , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaliplatin , Retrospective Studies , Survival Analysis , Treatment Outcome
15.
J Clin Oncol ; 24(1): 190-205, 2006 Jan 01.
Article in English | MEDLINE | ID: mdl-16326753

ABSTRACT

This year, for the first time, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances 2005: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant clinical research presented or published over the past year across all cancer types. ASCO embarked on this project to provide the public, patients, policymakers, and physicians with an accessible summary of the year's most important research advances. While not intended to serve as a comprehensive review, this report provides a year-end snapshot of research that will have the greatest impact on patient care. As you will read, there is much good news from the front lines of cancer research. These pages report on new chemotherapy regimens that sharply reduce the risk of recurrence for very common cancers; the "coming of age" of targeted cancer therapies; promising studies of drugs to prevent cancer; and improvements in quality of life for people living with the disease, among many other advances. Survival rates for cancer are on the rise, increasing from 50% to 64% over the last 30 years. Cancer still exacts an enormous toll, however. Nearly 1.4 million Americans will be diagnosed this year, and some 570,000 will die of the disease. Clearly, more research is needed to find effective therapies for the most stubborn cancer types and stages. We need to know more about the long-term effects of newer, more targeted cancer therapies, some of which need to be taken over long periods of time. And we need to devote far greater attention to tracking and improving the care of the nearly 10 million cancer survivors in the United States today. Despite these and other challenges, the message of this report is one of hope. Through the dedicated, persistent pursuit of clinical research and participation in clinical trials by people with cancer, we steadily uncover new and better ways of treating, diagnosing, and preventing a disease that touches the lives of so many. I want to thank the Editorial Board members, the Specialty Editors, and the ASCO Cancer Communications Committee for their dedicated work to develop this report, and I hope you find it useful.


Subject(s)
Neoplasms/therapy , Breast Neoplasms/therapy , Central Nervous System Neoplasms/therapy , Female , Gastrointestinal Neoplasms/therapy , Genital Neoplasms, Female/therapy , Head and Neck Neoplasms/therapy , Hematologic Neoplasms/therapy , Humans , Lung Neoplasms/therapy , Medical Oncology , Neoplasms/diagnosis , Neoplasms/mortality , Neoplasms/prevention & control , Research , Skin Neoplasms/therapy , Urogenital Neoplasms/therapy
16.
Gastroenterol Clin Biol ; 30(12): 1349-53, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17211331

ABSTRACT

OBJECTIVES: To evaluate long-term survival of patients resected for primarily unresectable colorectal liver metastases downstaged by systemic chemotherapy. METHODS: Among a group of 82 patients with advanced colorectal cancer, 39 had unresectable liver metastases. After treatment with systemic 3-weekly 5FU/folinic acid/oxaliplatin chemotherapy, the outcome of 11 patients made resectable thanks to chemotherapy was compared to that of 28 patients who were not. Criteria for non-resectability consisted of diffuse bilobar invasion with inability to achieve complete resection, unilobar or bilobar invasion plus vascular extension (invasion of inferior vena cava or 2 supra-hepatic veins plus continuity with the 3rd) or involvment of hepatic pedicle. Before and after surgery, CT scan evaluation was performed every 2 months. Progression free survival was defined as the time between starting chemotherapy and recurrence of the disease. We used Kaplan-Meier survival curves and log-rank test for comparisons, P values were two-sided and considered significant if<0.05. RESULTS: Progression free survival times were 14 and 6 months, median overall survival were 60 and 18.5 months, respectively, in favour of secondary resected subjects. CONCLUSION: Considering the magnitude of the survival benefit, one may question the need and feasibility for trials to assess more formally the impact of surgery in that setting.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Combined Modality Therapy , Female , Fluorouracil/administration & dosage , Humans , Liver Neoplasms/surgery , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Survival Rate , Time Factors
17.
Lancet Oncol ; 6(7): 459-68, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15992694

ABSTRACT

BACKGROUND: Systemic adjuvant chemotherapy can improve overall survival and reduce the incidence of distant metastases for patients with advanced colon cancer. This study aimed to investigate whether regional chemotherapy (given by intraperitoneal or intraportal methods) combined with systemic chemotherapy was more effective than was systemic chemotherapy alone in terms of survival and recurrence for patients with stage II-III colorectal cancer. The study also compared systemic chemotherapy with fluorouracil and folinic acid with that of fluorouracil and levamisole. METHODS: During surgery, 753 patients with stage II-III colorectal cancer were randomly assigned to systemic chemotherapy alone (379 with fluorouracil and folinic acid, and 374 with fluorouracil and levamisole), and 748 to postoperative regional chemotherapy with fluorouracil followed by systemic chemotherapy with fluorouracil and folinic acid (n=368) or with fluorouracil and levamisole (n=380). Regional chemotherapy was given intraperitoneally (n=415) or intraportally (n=235) according to institution. The primary endpoint was 5-year overall survival. Secondary endpoints were 5-year disease-free survival and toxic effects. Analyses were by intention to treat. FINDINGS: Median follow-up was 6.8 years (range 0.0-10.1). 5-year overall survival was 72.3% (95% CI 69.0-75.6) for patients assigned regional and systemic chemotherapy, compared with 72.0% (68.7-75.3) for those assigned systemic chemotherapy alone (hazard ratio [HR] 0.97 [0.81-1.15], p=0.69). 5-year overall survival for all patients assigned fluorouracil and levamisole was 72.0% (68.7-75.2) compared with 72.3% (69.0-75.6) for all those assigned fluorouracil and folinic acid (HR 0.98 [0.82-1.17], p=0.81). The hazard ratios for 5-year disease-free survival were 0.94 (0.80-1.10) for regional versus non-regional treatment, and 0.92 (0.79-1.08) for all fluorouracil and levamisole versus fluorouracil and folinic acid. Grade 3-4 toxic effects were low in all groups. INTERPRETATION: Fluorouracil-based regional chemotherapy adds no further benefit to that obtained with systemic chemotherapy alone in patients with advanced colorectal cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Aged , Chemotherapy, Adjuvant , Chemotherapy, Cancer, Regional Perfusion , Combined Modality Therapy , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Levamisole/administration & dosage , Male , Middle Aged , Survival Analysis
18.
Curr Opin Oncol ; 17(4): 381-5, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15933474

ABSTRACT

PURPOSE OF REVIEW: Colon cancer is the second leading cause of cancer death in Western countries. Although most colon cancer patients will undergo curative surgery, survival, depending on the pathologic stage, varies from 30-60% for Dukes C to 60-80% for Dukes B. Until very recently, the absolute benefit for survival obtained with adjuvant therapy compared with control was about 6%. The present review analyzes the results of the new combination of 5-fluorouracil/leucovorin/oxaliplatin (MOSAIC study), the oral fluoropyrimidines, and the studies of genetic and molecular markers, attempting to identify the patients at risk of recurrence. RECENT FINDINGS: Both 5-fluorouracil/leucovorin/oxaliplatin and the oral fluoropyrimidines show a statistically significant benefit of experiments treatment compared with 5-fluorouracil/leucovorin and no treatment, respectively. A reduction of 23% in the risk of relapse (disease-free survival rates of 78.2% in the 5-fluorouracil/leucovorin/oxaliplatine arm compared with 72.9% for 5-fluorouracil/leucovorin; P = 0.002) for the former and an overall hazard ratio of 0.89 for survival (95% CI, 0.80-0.99; P = 0.04) and 0.85 for disease-free survival (95% CI, 0.77-0.93; P < 0.001) in favor of oral therapy compared with control. A review of the literature on translational research indicates that patients at risk of recurrence can be identified by a 23-gene signature as well as by the combination of p27, p53, and vascular endothelial growth factor molecular alterations. SUMMARY: The present review shows that adjuvant therapy of colon cancer is still improving and that the use of genetic/molecular markers together with the new targeted therapies has the potential to improve survival further.


Subject(s)
Antineoplastic Agents/therapeutic use , Colonic Neoplasms/drug therapy , Chemotherapy, Adjuvant , Humans
19.
Semin Oncol ; 32(6 Suppl 9): S59-62, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16399434

ABSTRACT

Despite staining positive for the epidermal growth factor receptor (EGFR), a significant number of EGFR-expressing colorectal cancers are resistant to cetuximab, a chimeric monoclonal antibody directed against EGFR. Activation of EGFR through the autophosphorylation of its tyrosine residues stimulates different signaling downstream pathways and may reflect the level of receptor utilization by the tumor. This study investigated activated/phosphorylated EGFR (pEGFR) in 23 patients with EGFR-positive metastatic colorectal cancer refractory to irinotecan and treated with cetuximab, alone or in combination with irinotecan. Seven patients received cetuximab, and 16 patients received cetuximab plus irinotecan. Among the 23 patients, six (26%) had a partial response, 10 (44%) had stable disease, and seven (30%) had progressive disease. Median duration of disease control (partial response + stable disease) was 6 months. Nineteen out of 20 EGFR-positive tumors (95%) stained positive for pEGFR and had a median pEGFR immunohistochemical score of 5. Disease control rates differed between patients with a pEGFR immunohistochemical score >or= 7 (7/7, 100%) and less than 7 (7/13, 53.8%), showing a trend toward higher disease control in patients with high levels of pEGFR (>or= 7) who were treated with cetuximab with or without irinotecan (P = .05).


Subject(s)
Adenocarcinoma/drug therapy , Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , ErbB Receptors/drug effects , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Cetuximab , Clinical Trials, Phase II as Topic , ErbB Receptors/metabolism , Female , Humans , Immunohistochemistry , Irinotecan , Male , Middle Aged , Phosphorylation
20.
N Engl J Med ; 351(4): 337-45, 2004 Jul 22.
Article in English | MEDLINE | ID: mdl-15269313

ABSTRACT

BACKGROUND: The epidermal growth factor receptor (EGFR), which participates in signaling pathways that are deregulated in cancer cells, commonly appears on colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We compared the efficacy of cetuximab in combination with irinotecan with that of cetuximab alone in metastatic colorectal cancer that was refractory to treatment with irinotecan. METHODS: We randomly assigned 329 patients whose disease had progressed during or within three months after treatment with an irinotecan-based regimen to receive either cetuximab and irinotecan (at the same dose and schedule as in a prestudy regimen [218 patients]) or cetuximab monotherapy (111 patients). In cases of disease progression, the addition of irinotecan to cetuximab monotherapy was permitted. The patients were evaluated radiologically for tumor response and were also evaluated for the time to tumor progression, survival, and side effects of treatment. RESULTS: The rate of response in the combination-therapy group was significantly higher than that in the monotherapy group (22.9 percent [95 percent confidence interval, 17.5 to 29.1 percent] vs. 10.8 percent [95 percent confidence interval, 5.7 to 18.1 percent], P=0.007). The median time to progression was significantly greater in the combination-therapy group (4.1 vs. 1.5 months, P<0.001 by the log-rank test). The median survival time was 8.6 months in the combination-therapy group and 6.9 months in the monotherapy group (P=0.48). Toxic effects were more frequent in the combination-therapy group, but their severity and incidence were similar to those that would be expected with irinotecan alone. CONCLUSIONS: Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory colorectal cancer.


Subject(s)
Adenocarcinoma/drug therapy , Antibodies, Monoclonal/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Camptothecin/administration & dosage , Colorectal Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/adverse effects , Cetuximab , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Disease Progression , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Exanthema/chemically induced , Female , Humans , Irinotecan , Male , Middle Aged , Neoplasm Metastasis , Single-Blind Method , Survival Analysis , Topoisomerase I Inhibitors
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