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E Van Cutsem

Publications and source records attributed to E Van Cutsem.

At least 55 records · Page 3Linked to original sources
PubMed2001

Clinical value of whole-body emission tomography in potentially curable colorectal liver metastases.

AIMS: In selected patients with colorectal liver metastases, hepatic resection offers an opportunity for cure, with a 25-38% 5-year survival rate. The aim of this prospective study was to evaluate whether patient selection could be improved with pre-operative whole-body 18-fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) scan. METHODS: Ninety-one consecutive patients were considered to be eligible for liver resection after investigation with conventional diagnostic methods (CDM). In all these patients a whole-body PET scan with FDG was performed prior to surgery. Follow-up was complete with a mean of 23 months (2 weeks-92 months). All PET images were reviewed blinded to intraoperative and follow-up data. RESULTS: PET confirmed liver metastases in 90 (99%) patients, while it provided additional information in 10 (11%) patients, i.e., seven intra-abdominal, and three extra-abdominal. PET falsely upstaged six (6.6%) patients in whom malignancy was excluded by additional investigation, at the time of surgery, or during follow-up. PET falsely understaged seven (7.7%) patients with small intra-abdominal lesions. CONCLUSION: In patients with potentially curable colorectal liver metastases according to conventional diagnostic methods, whole-body FDG-PET can be considered as a complementary examination in order to further select patients for potentially curative liver resection, and to optimize therapeutic strategy.

Adult↗
PubMed2001

Optimizing the use of irinotecan in colorectal cancer.

The introduction of new agents with novel mechanisms of action has led to considerable changes in the management of colorectal cancer in recent years. One of these novel agents, irinotecan, has been shown to offer survival benefits in both the first- and second-line treatment of advanced/metastatic colorectal cancer. Irinotecan monotherapy improves survival compared with both best supportive care and infused 5-fluorouracil (5-FU) in patients with 5-FU-pretreated disease, without impacting negatively on patients' quality of life. As a result, irinotecan monotherapy is now considered to be the standard treatment in this setting. Irinotecan in combination with 5-FU/leucovorin (LV) was subsequently evaluated as first-line therapy for metastatic colorectal cancer in two randomized, phase III studies. Both trials confirmed that irinotecan plus infused or bolus 5-FU/leucovorin LV provide a modest survival benefit without compromising patients' quality of life. Combined irinotecan/5-FU/LV represents a new standard in the first-line treatment of metastatic colorectal cancer. In an attempt to further improve efficacy and tolerability, recent studies have investigated irinotecan in combination with capecitabine as first-line treatment for colorectal cancer. The replacement of infused 5-FU with oral capecitabine provides a more convenient treatment option. A phase I study was conducted to establish the maximum tolerated dose, and demonstrated encouraging antitumor activity and a manageable safety profile with the combination. This article provides a brief overview of the pivotal clinical trial data for irinotecan and discusses how irinotecan-based therapy may be improved in the future. It also discusses potential optimization of irinotecan use through identification of patient subpopulations most likely to benefit from combination or sequential strategies, and the potential of new, oral agents such as capecitabine to replace i.v. 5-FU as a combination partner for irinotecan.

Antimetabolites, Antineoplastic↗
PubMed2000

Utility of positron emission tomography for the staging of patients with potentially operable esophageal carcinoma.

PURPOSE: A prospective study of preoperative tumor-node-metastasis staging of patients with esophageal cancer (EC) was designed to compare the accuracy of 18-F-fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) with conventional noninvasive modalities. PATIENTS AND METHODS: Seventy-four patients with carcinomas of the esophagus (n = 43) or gastroesophageal junction (n = 31) were studied. All patients underwent attenuation-corrected FDG-PET imaging, a spiral computed tomography (CT) scan, and an endoscopic ultrasound (EUS). RESULTS: FDG-PET demonstrated increased activity in the primary tumor in 70 of 74 patients (sensitivity: 95%). False-negative PET images were found in four patients with T1 lesions. Thirty-four patients (46%) had stage IV disease. FDG-PET had a higher accuracy for diagnosing stage IV disease compared with the combination of CT and EUS (82% v 64%, respectively; P: =.004). FDG-PET had additional diagnostic value in 16 (22%) of 74 patients by upstaging 11 (15%) and downstaging five (7%) patients. Thirty-nine (53%) of the 74 patients underwent a 2- or 3-field lymphadenectomy in conjunction with primary curative esophagectomy. In these patients, tumoral involvement was found in 21 local and 35 regional or distant lymph nodes (LN). For local LN, the sensitivity of FDG-PET was lower than EUS (33% v 81%, respectively; P: =.027), but the specificity may have been higher (89% v 67%, respectively; P: = not significant [NS]). For the assessment of regional and distant LN involvement, compared with the combined use of CT and EUS, FDG-PET had a higher specificity (90% v 98%, respectively; P: =. 025) and a similar sensitivity (46% v 43%, respectively; P: = NS). CONCLUSION: PET significantly improves the detection of stage IV disease in EC compared with the conventional staging modalities. PET improves diagnostic specificity for LN staging.

Adenocarcinoma↗
PubMed2000

New directions in the treatment of colorectal cancer: a look to the future.

Today, adjuvant 5-fluorouracil based therapy is known to significantly reduce the relapse rates and the risks of dying from resected colon cancer; chemotherapy approximately doubles overall survival of advanced colorectal cancer and second line treatment prolongs the survival of patients compared with best supportive care. At the molecular level a number of key genes are often mutated in cancer of the colon and some of these key regulators of apoptosis are discussed (p53 and bcl-2 family of proteins). Dihydropyrimidine dehydrogenase (DPD) activity may be a potential factor controlling fluorouracil (FU) responsiveness at the tumoral level and its importance is stressed. The rationale of combining FU with DPD inhibitors is fairly strong. Ethynyluracil, UFT and S1 pursue this strategy while capecitabine has another the rationale. Drug resistance should be at least partially overcome by combination chemotherapy (FU plus mitomycin, oxaliplatin, irinotecan) and combined modality (FU+RT) regimens. Improved surgical techniques and radiotherapy have substantially decreased local failure rates for rectal cancers. Finally, innovative treatment modalities such as anti-angiogenetic and antimetastatic agents, farnesyl transferase inhibitors, vaccine and gene therapy are in early clinical trials.

Antimetabolites, Antineoplastic↗
PubMed2000

The utility of positron emission tomography for the diagnosis and staging of recurrent esophageal cancer.

OBJECTIVE: To study the utility of whole-body positron emission tomography with (18)F-fluoro-deoxy-D -glucose (FDG-PET) for the evaluation of recurrence after curative resection of cancer of the esophagus or gastroesophageal junction. METHODS: Forty-one patients with a clinical or radiologic suspicion of recurrent disease underwent conventional diagnostic work-up, including a spiral computed tomographic scan, an endoscopic ultrasound, and a dedicated whole-body FDG-PET. PET lesions were classified as equivocal or suspicious recurrence. The conventional diagnostic work-up and PET findings were correlated with pathology or with radiologic and clinical follow-up. Equivocal lesions were classified as positive. RESULTS: Forty recurrences were found in 33 patients. The lesions were perianastomotic (n = 9), regional (n = 12), and at distant sites (n = 19). For the diagnosis of a perianastomotic recurrence, the sensitivity, specificity, and accuracy of FDG-PET were 100%, 57%, and 74%, versus 100%, 93%, and 96% for conventional diagnostic work-up, respectively (P = not significant). False-positive PET lesions were found in patients with a progressive anastomotic stenosis requiring repetitive endoscopic dilatation. For the diagnosis of regional and distant recurrences, the sensitivity, specificity, and accuracy of PET were 94%, 82%, and 87%, versus 81% (P = not significant), 82% (P = not significant), and 81% (P =.0771) for conventional diagnostic work-up. All false-positive PET lesions (n = 4) had been reported as equivocal. On a patient base, PET provided additional information in 11 of 41 (27%) patients. A major impact on diagnosis was found in 5 patients with equivocal or negative findings on complete diagnostic work-up in whom PET provided a true-positive diagnosis. In 5 other patients the diagnosis was staged upward from localized to extended recurrent disease, and in 1 patient with an equivocal complete diagnostic work-up, PET correctly excluded malignancy. CONCLUSION: FDG-PET allows a highly sensitive diagnosis and accurate whole-body staging of symptomatic recurrent esophageal cancer. Further studies in asymptomatic patients are needed to assess the potential benefit on survival.

Adenocarcinoma↗
PubMed2000

Histopathologic validation of lymph node staging with FDG-PET scan in cancer of the esophagus and gastroesophageal junction: A prospective study based on primary surgery with extensive lymphadenectomy.

OBJECTIVE: To assess the value of positron emission tomography with 18fluorodeoxyglucose (FDG-PET) for preoperative lymph node staging of patients with primary cancer of the esophagus and gastroesophageal junction. SUMMARY BACKGROUND DATA: FDG-PET appears to be a promising tool in the preoperative staging of cancer of the esophagus and gastroesophageal junction. Recent reports indicate a higher sensitivity and specificity for detection of stage IV disease and a higher specificity for diagnosis of lymph node involvement compared with the standard use of computed tomography and endoscopic ultrasound. METHODS: Forty-two patients entered the prospective study. All underwent attenuation-corrected FDG-PET imaging of the neck, thorax, and upper abdomen, a spiral computed tomography scan, and an endoscopic ultrasound. The gold standard consisted exclusively of the histology of sampled nodes obtained by extensive two-field or three-field lymphadenectomies (n = 39) or from guided biopsies of suspicious distant nodes indicated by imaging (n = 3). RESULTS: The FDG-PET scan had lower accuracy for the diagnosis of locoregional nodes (N1-2) than combined computed tomography and endoscopic ultrasound (48% vs. 69%) because of a significant lack of sensitivity (22% vs. 83%). The accuracy for distant nodal metastasis (M+Ly), however, was significantly higher for FDG-PET than the combined use of computed tomography and endoscopic ultrasound (86% vs. 62%). Sensitivity was not significantly different, but specificity was greater (90% vs. 69%). The FDG-PET scan correctly upstaged five patients (12%) from N1-2 stage to M+Ly stage. One patient was falsely downstaged by FDG-PET scanning. CONCLUSIONS: FDG-PET scanning improves the clinical staging of lymph node involvement based on the increased detection of distant nodal metastases and on the superior specificity compared with conventional imaging modalities.

Adult↗
PubMed2000

Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group.

PURPOSE: To compare the efficacy and tolerability of etoposide, leucovorin, and bolus fluorouracil (ELF) or infusional fluorouracil plus cisplatin (FUP) with that of the reference protocol of fluorouracil, doxorubicin, and methotrexate (FAMTX) in advanced gastric cancer. PATIENTS AND METHODS: A total of 399 patients with advanced adenocarcinoma of the stomach were randomized and analyzed for toxicity, tumor response, and progression-free and overall survival. Only reviewed and confirmed responses were considered. The analysis of remission was based on assessable patients with documented measurable lesions. The intent-to-treat principle, log-rank test, and Cox regression model were used for the statistical analysis of time-to-event end points. RESULTS: The overall response rate for 245 eligible patients with measurable disease was 9% with ELF, 20% with FUP, and 12% with FAMTX, with no significant differences. One hundred twelve patients were eligible for efficacy in assessable, nonmeasurable disease. No change was observed in 66% of patients treated with ELF, 56% with FUP, and 55% with FAMTX. Two patients achieved a complete tumor regression (one each for ELF and FAMTX). With a median follow-up time of 4.5 years, the median survival times were 7.2 months with ELF, 7.2 months with FUP, and 6.7 months with FAMTX, respectively, with no significant differences. Nonhematologic and hematologic toxicities of ELF, FUP, and FAMTX were acceptable, with neutropenia being the major toxicity for all three regimens. Seven treatment-related deaths occurred (two with FUP and five with FAMTX). CONCLUSION: All three investigated regimens demonstrate modest clinical efficacy and should not be regarded as standard treatment for advanced gastric cancer. New strategies should be considered to achieve a better clinical efficacy in the treatment of advanced gastric cancer.

Adenocarcinoma↗
PubMed2000

Capecitabine, an oral fluoropyrimidine carbamate with substantial activity in advanced colorectal cancer: results of a randomized phase II study.

PURPOSE: To evaluate in patients with advanced colorectal cancer (CRC) three treatment regimens of oral capecitabine in order to select the most appropriate regimen for testing in phase III. PATIENTS AND METHODS: Three capecitabine schedules were evaluated in a randomized phase II design: arm A, 1,331 mg/m(2)/d bid continuously; arm B, 2,510 mg/m(2)/d bid intermittently (2 weeks on/1 week off); and arm C, 1,657 mg/m(2)/d plus oral leucovorin 60 mg/d bid intermittently (2 weeks on/1 week off). RESULTS: One hundred nine patients were randomized; 39 patients were assessable for efficacy in arm A, 34 in arm B, and 35 in arm C. Patient characteristics were balanced in the arms. Confirmed tumor responses (partial response [PR] + complete response [CR]) were reported for eight patients with two CRs (21%; 95% confidence interval [CI], 9% to 36%) in arm A, eight patients with one CR (24%; 95% CI, 11% to 41%) in arm B, and eight patients with two CRs (23%; 95% CI, 10% to 40%) in arm C. Median times to progression (TTP) in arms A, B, and C were 127, 230, and 165 days, respectively. Overall, more toxicity was seen with capecitabine plus leucovorin, particularly diarrhea and hand-foot syndrome. There was no grade 3 or 4 marrow toxicity. CONCLUSION: Capecitabine offers a new, effective treatment option as an oral single agent in advanced CRC. Promising overall response rates were reported for all three regimens. The addition of leucovorin to the intermittent regimen had no marked effect on tumor response or median TTP. The intermittent single-agent capecitabine schedule is proposed for phase III evaluation, based on considerations of toxicity, dose-intensity, response rate, and TTP.

Administration, Oral↗
PubMed1999

Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor).

Aggressive fibromatosis (also called desmoid tumor) occurs as a sporadic lesion or as part of Familial Adenomatous Polyposis, which is caused by germ line mutations in the Adenomatous polyposis Coli (APC) gene. APC is involved in the regulation of the cellular level of beta-catenin, which is a mediator in Wnt signaling. Mutational analysis of the beta-catenin and APC genes was performed in 42 sporadic aggressive fibromatoses. Nine tumors had mutations in APC, and 22 had a point mutation in beta-catenin at either codon 45 or codon 41 (producing a stabilized beta-catenin protein product). Immunohistochemistry showed an elevated beta-catenin protein level in all tumors, regardless of mutational status. Beta-catenin localized to the nucleus, and was not tyrosine phosphorylated in the six tumors in which this was tested. The demonstration of mutations in two mediators in the Wnt-APC-beta-catenin pathway implicates beta-catenin stabilization as the key factor in the pathogenesis of aggressive fibromatosis. This is the first demonstration of somatic beta-catenin mutations in a locally invasive, but non metastatic lesion composed of spindle cells, illustrating the importance of beta-catenin stabilization in a variety of cell types and neoplastic processes. Moreover, this tumor has one of the highest reported frequencies of beta-catenin mutations of any tumor type.

Base Sequence↗
PubMed1999

Screening applications for MRI in the detection of upper abdominal disease: comparative study of non-contrast-enhanced single-shot MRI and contrast-enhanced helical CT.

PURPOSE: To compare the value of 'push-button' single-shot non-contrast-enhanced MRI and contrast-enhanced helical CT for detection of upper abdominal disease. METHODS: In 120 patients, images obtained with non contrast-enhanced single-shot MRI (T2: double echo HASTE, and T1: turbo FLASH) and contrast-enhanced helical CT were compared. Lesions or abnormalities were divided in 8 anatomical categories (1: liver; 2: pancreatobiliary; 3: kidney/adrenal gland; 4: retroperitoneum; 5: vascular; 6: spleen; 7: gastrointestinal tract and peritoneum; 8: base of thorax) and classified as follows: 2: seen at MRI only; 1: better seen at MRI; 0: no difference; -1: better seen at CT; -2: seen at CT only. Also recorded were the 'door-to-door' examination times. RESULTS: Of a total of 629 abnormalities, 594 were detected at MRI (94 %) and 536 at CT (85 %). CT offered better results in two categories only: retroperitoneum (mean score: -0.68) and vascular (mean score -0.87). Mean examination times were 19 min for CT and 14.8 min for MRI. CONCLUSION: Unenhanced single-shot MRI is a valuable first step of a comprehensive upper abdominal MR exam and may even be the final step in many patients.

Abdomen↗
PubMed1999

Transcatheter embolization of hepatic arteriovenous fistulas in Rendu-Osler-Weber disease: a case report and review of the literature.

A patient with hereditary hemorrhagic telangiectasia and diffuse intrahepatic arteriovenous fistulas developed secondary high-output ventricular failure and pulmonary hypertension. A serial staged hepatic arterial coil embolization was performed with long-term resultant haemodynamic and clinical improvement. The methods of this procedure and related complications are discussed.

Angiography↗
PubMed1999

Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU).

The aim of this prospective study was to assess the efficacy, clinical benefit and safety of CPT-11 (irinotecan) in patients with stringently-defined 5-fluorouracil-resistant metastatic colorectal cancer (CRC). 107 patients with documented progression of metastatic CRC during 5-FU were treated with CPT-11 350 mg/m2 once every 3 weeks in a multicentre phase II study. Tumour response and toxicity were assessed using WHO criteria. Changes in performance status (PS), weight and pain were also measured. The WHO response rate was 13/95 (13.7%, 95% CI 7.5% to 22.3%) eligible patients with a median duration of response of 8.5 months (37 weeks, range: 18-53+). There was also a high rate of disease stabilisation (44.2%) with a median duration of 4.8 months. The probability of being free of progression at 4 months was 50%. Median survival from first administration of CPT-11 was 10.4 months or 45 weeks (range: 3-66+ weeks). There was weight stabilisation or gain in 81% (73/90) of patients, a favourable outcome in PS in 91% (82/90) (improvement of WHO PS 2 or stabilisation of PS 0-1), and pain relief in 54% (26/48). There were no toxic deaths. Neutropenia was short-lasting and non-cumulative. Diarrhoea grade > or = 3 occurred in 7% of cycles and 28/107 (26%) of patients. CPT-11 350 mg/m2 once every 3 weeks has an encouraging degree of activity in progressive metastatic CRC truly resistant to 5-FU with a relatively high rate of tumour growth control translated into clinical benefit. The toxicity profile of CPT-11 is becoming better understood and has been considerably improved.

Adult↗
PubMed1999

Raltitrexed (Tomudex) in combination treatment for colorectal cancer: new perspectives.

In recent years, significant advances have been achieved in the treatment of colorectal cancer, including the use of adjuvant chemotherapy following surgery in patients with colon cancer and the use of palliative chemotherapy for metastatic disease. Further potential for improvements in outcome for patients with colorectal cancer is provided by the introduction of new agents in combined treatment modalities. Although some of these new agents, such as raltitrexed, oxaliplatin and irinotecan, are active in colorectal cancer, single-agent therapy as first-line treatment has failed to demonstrate a substantial increase in survival. However, preclinical studies have indicated that combination treatments have the potential benefit of enhanced response rates. One such agent, raltitrexed, is currently under investigation in combination with 5-FU (bolus and infusional), oxaliplatin, cisplatin, irinotecan and anthracyclines, principally in patients with advanced colorectal cancer, but also in patients with other tumours. Similarly, combinations of adjuvant or neo-adjuvant radiotherapy and chemotherapy are being investigated and can offer a benefit in the treatment of rectal, oesophageal, pancreatic and gastric cancer. Promise for the future, therefore, appears to lie in combined treatment modalities which are expected to provide superior alternatives to current standard treatments.

Antibiotics, Antineoplastic↗
PubMed1999

Irinotecan in second-line treatment of metastatic colorectal cancer: improved survival and cost-effect compared with infusional 5-FU.

In a recent multicentre, randomised, controlled, open-label study (Rougier and colleagues, Lancet 1998, 352, 1407-1412), irinotecan significantly increased survival without any deterioration in quality of life compared with best-estimated infusional 5-fluorouracil (5-FU) therapy in the setting of second-line treatment for metastatic colorectal cancer. The aim of the cost-effectiveness analysis reported here was to compare the economic implications, from a U.K. perspective, of replacing 5-FU therapy [either as a single agent (Lokich regimen, B2) or in combination with folinic acid (de Gramont regimen, B1, or AIO regimen, B3)] with irinotecan as second-line therapy for metastatic colorectal cancer. Resource utilisation data collected prospectively during the study, supplemented by both a questionnaire to investigators and local expert clinical opinion, were used as a basis for estimating cumulative drug dosage, chemotherapy administration and treatment of complications. Drug acquisition costs were derived from the British National Formulary (March 1998), and unit costs for clinical consultation and services were derived from relevant 1996/1997 cost databases. Although cumulative drug acquisition costs per patient were higher with irinotecan than with infusional 5-FU therapy, these were at least partially offset by lower cumulative costs per patient associated with administration of therapy and treatment of complications in the irinotecan arm than in the 5-FU arm. Based on the incremental costs per life year gained (LYG), irinotecan was considered to be cost-effective by commonly accepted criteria compared with either the B1 or B2 regimens. Irinotecan was cost-saving compared with the B3 regimen (that is significant survival gain and a reduction in costs). Thus, not only is there strong evidence for the use of irinotecan as standard second-line therapy in metastatic colorectal cancer,but the results of this prospective economic evaluation have shown that irinotecan also represents good value for money in this clinical setting.

Adult↗