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Ian Chau

Publications and source records attributed to Ian Chau.

18 recordsLinked to original sources
PubMed2006

Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer.

PURPOSE: To evaluate neoadjuvant capecitabine/oxaliplatin before chemoradiotherapy (CRT) and total mesorectal excision (TME) in newly diagnosed patients with magnetic resonance imaging (MRI) -defined poor-risk rectal cancer. PATIENTS AND METHODS: MRI criteria for poor-risk rectal cancer were tumors within 1 mm of mesorectal fascia (ie, circumferential resection margin threatened), T3 tumors at or below levators, tumors extending > or = 5 mm into perirectal fat, T4 tumors, and T1-4N2 tumors. Patients received 12 weeks of neoadjuvant capecitabine/oxaliplatin followed by concomitant capecitabine and radiotherapy. TME was planned 6 weeks after CRT. Postoperatively, patients received another 12 weeks of capecitabine. RESULTS: Between November 2001 and August 2004, 77 eligible patients were recruited. After neoadjuvant capecitabine/oxaliplatin, the radiologic response rate was 88%. In addition, 86% of patients had symptomatic responses in a median of 32 days (ie, just over one cycle of capecitabine/oxaliplatin). After CRT, the tumor response rate was increased to 97%. Three patients remained inoperable. Sixty-seven patients proceeded to TME, and all but one patient had R0 resection. Pathologic complete response was observed in 16 patients (24%; 95% CI, 14% to 36%), and in an additional 32 patients (48%), only microscopic tumor foci were found on surgical specimens. Four deaths occurred during neoadjuvant capecitabine/oxaliplatin therapy as a result of pulmonary embolism, ischemic heart disease, sudden death with history of chest pain, and neutropenic colitis. CONCLUSION: Capecitabine/oxaliplatin before synchronous CRT and TME results in substantial tumor regression, rapid symptomatic response, and achievement of R0 resection.

Adult↗
PubMed2006

Folate metabolism polymorphisms influence risk of colorectal adenoma recurrence.

Folate intake is inversely related to risk of developing colorectal neoplasia. Associations between risk of colorectal neoplasia and polymorphisms in genes coding for enzymes involved in folate metabolism have also been reported, suggesting a relationship between genotype and development of colorectal neoplasia. To further investigate the effects of folate metabolism genotypes on colorectal neoplasia, we genotyped 546 patients participating in a randomized controlled trial of folate supplementation for the prevention of colorectal adenoma recurrence. A significantly reduced risk of recurrence was observed in patients heterozygous for the MTRR A66G polymorphism [relative risk (RR), 0.64; 95% confidence interval (95% CI), 0.46-0.90] or heterozygous for the MTHFR A1298C polymorphism (RR, 0.71; 95% CI, 0.52-0.97). Furthermore, a significant reduction in recurrence risk was seen in MTRR A66G heterozygotes who received folate supplements but not in those who did not receive folate. Patients heterozygous for the MTHFR C677T polymorphism had a nonsignificant risk reduction (RR, 0.92; 95% CI, 0.69-1.23), as did patients with one or two variant alleles for the MTR A2756G polymorphism (RR, 0.82; 95% CI, 0.60-1.12). No influence on recurrence risk was observed for the TSER, TSER 3R G>C, and TS 1494del6 variants. These findings provide additional support for the hypothesis that germ line variants in folate metabolism genes influence the development of colorectal adenomas.

Adenoma↗
PubMed2005

Longitudinal quality of life and quality adjusted survival in a randomised controlled trial comparing six months of bolus fluorouracil/leucovorin vs. twelve weeks of protracted venous infusion fluorouracil as adjuvant chemotherapy for colorectal cancer.

Longitudinal quality of life (QOL) assessment is infrequently made in adjuvant therapy for colorectal cancer (CRC). This analysis aims to assess QOL and quality adjusted survival (QAS) in patients receiving adjuvant 5-FU for stage II and III CRC. We performed a multicentre study in which 801 patients were randomised to 6 months of bolus 5-FU/leucovorin (LV n = 404) or 12 weeks of protracted venous infusion (PVI) 5-FU (n = 397). There were significant differences in the deterioration of QOL scores at week 2 with bolus 5-FU/LV compared to PVI 5-FU (P < 0.001), coinciding with toxicity peak during the first cycle. Following week 12, global QOL recovered to baseline when PVI 5-FU was stopped but this was delayed with bolus 5-FU/LV until completion at week 24. QOL scores significantly improved in both arms during follow-up (P < 0.001) and reached a plateau by year 1 without incremental improvement between years 2 and 5. There was a trend towards better QAS with PVI 5-FU. Twelve weeks of adjuvant PVI 5-FU was associated with significantly better QOL during treatment and faster time to recovery compared to 6 months of bolus 5-FU/LV.

Adult↗
PubMed2004

A randomized trial comparing defined-duration with continuous irinotecan until disease progression in fluoropyrimidine and thymidylate synthase inhibitor-resistant advanced colorectal cancer.

PURPOSE: Irinotecan given until disease progression is an accepted standard treatment for advanced colorectal cancer (CRC) resistant to fluoropyrimidines. It is not known whether a predefined period of irinotecan treatment would result in similar duration of disease control. We performed a multicenter phase III trial to compare the two policies of defined-duration versus continuous irinotecan treatment. PATIENTS AND METHODS: Three hundred thirty-three eligible patients with advanced CRC progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospectively registered. After receiving eight cycles of irinotecan given at 350 mg/m2 once every 3 weeks, 55 patients with responding or stable disease were randomly assigned to stop irinotecan (n = 30) or continue until disease progression (n = 25). Registered patients were not randomly assigned predominantly due to disease progression (n = 236) and intolerable toxicity (n = 38). RESULTS: From the time of random assignment, there were no differences in failure-free survival (P = .999) or overall survival (P = .11) between the two arms. No difference was seen in mean global health status quality-of-life score between the two arms at 12 weeks after random assignment. No grade 3 diarrhea and febrile neutropenia was seen in the continue-irinotecan arm after random assignment. CONCLUSION: For most patients, the decision to continue on irinotecan beyond 24 weeks is influenced by disease progression or treatment-related toxicity. However, for 17% of patients in whom this decision is clinically relevant, there seems to be little benefit from continuing irinotecan, though the drug was well tolerated without any deterioration in quality of life.

Adult↗
PubMed2004

Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer.

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.

Adenocarcinoma↗
PubMed2004

Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer--pooled analysis from three multicenter, randomized, controlled trials using individual patient data.

PURPOSE: To identify baseline prognostic factors and assess whether pretreatment quality of life (QoL) predicts survival in patients with locally advanced or metastatic esophago-gastric cancer. PATIENTS AND METHODS: Between 1992 and 2001, 1,080 patients were enrolled into three randomized, controlled trials assessing fluorouracil-based combination chemotherapy. All patients were required to complete the European Organization for Research and Treatment of Cancer core QoL questionnaire before random assignment. RESULTS: Of the 1080 patients randomly assigned, 979 (91%) died. Four independent poor prognostic factors were identified by multivariate analysis: performance status >or= 2 (hazard ratio [HR], 1.58; 99% CI, 1.25 to 1.98), liver metastases (HR, 1.41; 99%CI, 1.14 to 1.74), peritoneal metastases (HR, 1.33; 99%CI, 1.01 to 1.74) and alkaline phosphatase >or= 100 U/L (HR, 1.41; 99% CI, 1.14 to 1.76). A prognostic index was constructed dividing patients into good (no risk factor), moderate (one or two risk factors) or poor (three or four risk factors) risk groups. One-year survival for good, moderate, and poor risk groups were 48.5%, 25.7%, and 11%, respectively, and the survival differences among these groups were highly significant (P <.00001). Compared with the good risk group, the moderate risk group had nearly twice the risk of death, and the poor risk group had 3.5-fold increased risk of death. Pretreatment physical (P =.003), role functioning (P <.001), and global QoL (P <.001) predicted survival. CONCLUSION: Four poor prognostic factors were identified and a simple prognostic index was devised. Information from this analysis can be used to aid clinical decision-making, help individual patient risk stratification, and serve as benchmark for the planning for future phase III trials.

Adult↗
PubMed2004

The value of routine serum carcino-embryonic antigen measurement and computed tomography in the surveillance of patients after adjuvant chemotherapy for colorectal cancer.

PURPOSE: This analysis aims to evaluate routine carcino-embryonic antigen (CEA) and computed tomography (CT) of thorax, abdomen, and pelvis as part of protocol-specified follow-up policy for colorectal cancer (CRC). PATIENTS AND METHODS: Patients with resected stage II and III CRC were randomly assigned to bolus fluorouracil/leucovorin or protracted venous infusion fluorouracil. Following completion of chemotherapy, patients were seen in clinic at regular intervals for 5 years. CEA was measured at each clinic visit, and CT of thorax, abdomen, and pelvis was performed at 12 and 24 months after commencement of chemotherapy. RESULTS: Between 1993 and 1999, 530 patients were recruited. The median follow-up was 5.6 years. Disease relapses were observed in 154 patients. Relapses were detected by symptoms (n = 65), CEA (n = 45), CT (n = 49), and others (n = 9). Fourteen patients, whose relapses were detected by CT, had a concomitant elevation of CEA and were included in both groups. The CT-detected group had a better survival compared with the symptomatic group from the time of relapse (P =.0046). Thirty-three patients (21%) proceeded to potentially curative surgery for relapse and enjoyed a better survival than those who did not (P <.00001). For patients who underwent hepatic or pulmonary metastatic resection, 13 (26.5%) were in the CT group, eight (17.8%) in the CEA group, and only two (3.1%) in the symptomatic group (CT v symptomatic, P <.001; CEA v symptomatic, P =.015). CONCLUSION: Surveillance CT and CEA are valuable components of postoperative follow-up in stage II and III colorectal cancer.

Adult↗
PubMed2004

The vital role of education and information in patients receiving capecitabine (Xeloda).

Use of oral capecitabine (Xeloda) as home-based therapy leads to savings in healthcare resources and costs and oral chemotherapy is preferred by many cancer patients over intravenous (i.v.) 5-FU. The demands of patient management for oral therapy differ significantly from those of i.v. chemotherapy. Consequently, cancer programmes have begun to implement strategies to meet these unique demands, offer educational programmes for clinicians who prescribe capecitabine, and consider potential changes in staff responsibilities. To encourage patients to take an active part in their care, which is vital with home-based oral therapy, they must be properly informed about their treatment. Patient information needs to be specific for the cancer type and relevant for the country. Various tools have been developed, including prescription guides, diary cards and support kits, which are useful in reinforcing verbal discussions about the use of capecitabine and in helping patients to manage their treatment. Nurses have a vital role to play in encouraging the optimal use of capecitabine and prompt management of adverse events, thereby enabling the patient to achieve a better clinical outcome and maintain an improved quality of life in the home environment.

Administration, Oral↗
PubMed2003

Matrix metalloproteinase inhibitors--an emphasis on gastrointestinal malignancies.

Gastrointestinal malignancies are the commonest sites of human cancer collectively. Improved understanding of tumour biology in the last few decades has allowed the identification of cellular pathways responsible for the autonomous growth and replication in cancer cells. There is considerable preclinical evidence implicating matrix metalloproteinases (MMPs) in cancer dissemination and tumour angiogenesis. Effective MMP inhibitors (MMPIs) may, therefore, hold an important key in the treatment of gastrointestinal cancers. MMPIs are cytostatic agents and traditional values of tumour regression may not be the best measures of treatment efficacy. Biological correlation studies are increasingly being incorporated into the early development of these agents, but many of these studies lack preclinical validation and are often chosen on availability rather than biological plausibility. Disappointing results with many MMPIs that have entered phase III testing so far would prompt for identification of reliable surrogate biomarkers and incorporation of functional imaging in the clinical development of matrix metalloproteinase inhibitors in gastrointestinal malignancies. In this review, the integral part in which MMPs are involved in cancer growth and metastases will be presented. This is then followed by a discussion of the challenges that clinicians are facing in assessing the efficacy of MMPIs and finally a review of the clinical studies of the synthetic MMPIs in development.

Gastrointestinal Neoplasms↗
PubMed2003

Gemcitabine, cisplatin and methylprednisolone chemotherapy (GEM-P) is an effective regimen in patients with poor prognostic primary progressive or multiply relapsed Hodgkin's and non-Hodgkin's lymphoma.

This study was designed to assess the efficacy and safety of gemcitabine, cisplatin and methylprednisolone (GEM-P) for patients with relapsed or refractory Hodgkin's disease (HD) and non-Hodgkin's lymphoma. Twenty-one patients were treated with gemcitabine (1000 mg/m2 d 1, 8 and 15), cisplatin (100 mg/m2 d 15) and methylprednisolone (1000 mg d 1-5) given every 28 d. Of these, 20 patients were evaluable for response. The median age was 38 years (range 17-64 years). Histological subtypes were: nodular sclerosing HD (n = 10), diffuse large B cell (n = 5), T cell-rich B cell (n = 2), follicular (n = 2), mantle cell (n = 1) and enteropathy-associated T-cell lymphoma (n = 1). The median remission duration prior to receiving GEM-P was only 42 d. The overall objective response rate was 80%[95% confidence interval (CI): 56-94%], including five complete and 11 partial responses. GEM-P induced responses in all histological subtypes, primary progressive disease and patients who had received a previous autograft. The only grade 3-4 toxicity was myelosuppression. However, no cases of febrile neutropenia or haemorrhage with thrombocytopenia were encountered. Median survival has not yet been reached and survival probability at 1 year was 60.8% (95% CI: 31.9-80.5%). In conclusion, GEM-P is a novel combination salvage therapy for poor-prognostic primary progressive or multiply relapsed lymphoma patients. It has clinically significant activity with a favourable toxicity profile.

Adolescent↗
PubMed2003

Overview of preoperative and postoperative therapy for colorectal cancer: the European and United States perspectives.

Surgery is the primary modality for cure in patients with localized colorectal cancer. However, despite potential curative surgery, the risk of recurrence is high. In colon cancer, the role of adjuvant chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV) is now established in stage III disease. The benefit of adjuvant treatment in stage II disease is likely to be small, and studies performed thus far have been generally underpowered to detect what might be a clinically significant effect on survival. Whereas bolus scheduling of 5-FU and LV is favored in North America, infusion of 5-FU/LV is preferred in Europe. Indeed, infused 5-FU/LV may be a safer partner with new drugs such as oxaliplatin and irinotecan. Oral fluoropyrimidines are attractive agents that might one day replace parenteral 5-FU. In rectal cancer, postoperative combined chemoradiation was recommended as standard practice in stages II and III disease. Despite a lack of randomized data demonstrating clinical benefit, preoperative chemoradiation has been increasingly used in patients with T3 disease in North America. However, preoperative radiation therapy is more frequently used in Europe. There are discrepancies in pathologic reporting of circumferential resection margin involvement and lymph node status between the United States and Europe. Standardized reporting with improved preoperative imaging would allow patients with truly early-stage disease to undergo more conservative management and be spared the morbidity and mortality of unnecessary adjuvant or neoadjuvant treatment.

Chemotherapy, Adjuvant↗
PubMed2003

Impact of 5-fluorouracil rechallenge on subsequent response and survival in advanced colorectal cancer: pooled analysis from three consecutive randomized controlled trials.

The aim of this analysis is to evaluate the effect of 5-fluorouracil (5-FU) rechallenge on subsequent response and survival in patients with advanced colorectal cancer (CRC). Between April 1992 and August 1998, 613 patients were enrolled into 3 consecutive prospective randomized controlled trials assessing first-line infused 5-FU in patients with advanced CRC. All patients had a planned maximum treatment period of 6 months. Those with responding or stable disease at the end of 6 months were observed off treatment. On subsequent disease progression, patients were retreated with 5-FU alone (5-FU group) or 5-FU plus mitomycin C (MMC group). Ninety-three patients have been retreated (5-FU group, n = 71; MMC group, n = 22). The median age was 60 years (range, 38-79 years), and the median time to rechallenge was 11.7 months (5-FU group, 11.7 months; MMC group, 11.4 months). Seventeen percent of patients had an objective response to rechallenge (5-FU group, 13%; MMC group, 27%). The median survival was 14.8 months (5-FU group, 15.2 months; MMC group, 10.5 months; log-rank test, P = 0.23) and the median failure-free survival was 5.4 months (5-FU group, 5.6 months; MMC group, 3.7 months; log-rank test, P = 0.06). On multivariate analysis, a prolonged treatment-free interval of > 12 months (hazard ratio [HR], 0.57; 95% CI, 0.35-0.94; P = 0.027) and good performance status of 0/1 (HR, 0.38; 95% CI, 0.22-0.68; P = 0.001) were associated with better overall survival. In conclusion, a proportion of patients who experienced a prolonged period of tumor control with first-line infused 5-FU therapy and had a planned treatment interruption, retained 5-FU sensitivity and had prolonged survival with 5-FU rechallenge.

Adult↗
PubMed2002

Multicenter randomized phase III trial comparing protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin in inoperable pancreatic cancer.

PURPOSE: To compare protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin (MMC) in patients with advanced pancreatic cancer in a multicenter, prospectively randomized study. PATIENTS AND METHODS: Two hundred eight patients were randomized to PVI 5-FU (300 mg/m(2)/d for a maximum of 24 weeks) or PVI 5-FU plus MMC (7 mg/m(2) every 6 weeks for four courses). The major end points were tumor response, survival, toxicity, and quality of life (QOL). RESULTS: The two treatment groups were balanced for baseline demographic factors, and 62% had metastatic disease. The overall response rate was 8.4% (95% confidence interval [CI]) 3.2% to 13.7% for patients treated with PVI 5-FU alone compared with 17.6%; 95% CI 10.3% to 25.1% for PVI 5-FU plus MMC (P =.04). Median failure-free survival was 2.8 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC (P =.14). Median survival was 5.1 months for PVI 5-FU and 6.5 months for PVI 5-FU plus MMC (P =.34). Toxicities in both arms were mild. There was an increased incidence of neutropenia in the 5-FU plus MMC arm (P <.01), although no differences in infection were seen. No patients developed hemolytic uremic syndrome. Global QOL improved significantly after 24 weeks of treatment compared with baseline for patients receiving 5-FU plus MMC, although there was no statistically significant difference in QOL between arms. CONCLUSION: PVI 5-FU plus MMC resulted in a superior response rate in comparison with PVI 5-FU alone in advanced pancreatic cancer, but this did not translate into a survival advantage. These results emphasize the importance of chemotherapy in this setting and the continuing value of the fluoropyrimidines in pancreatic cancer.

Adult↗
PubMed2002

Adjuvant therapy in colon cancer: current status and future directions.

The role of adjuvant chemotherapy in patients with stage III colon cancer is now well established and 5-FU/LV should be the reference regimen to which new drugs are tested against in the adjuvant setting. In stage II colon cancer, because the risk of recurrence is lower, any absolute benefit of chemotherapy is likely to be less than in stage III disease. The studies performed so far have been generally underpowered to detect what might be a clinically significant effect on survival. Molecular profiling of tumours may identify individuals more likely to benefit from adjuvant therapy and tailor individual treatment in the future. After potential curative treatment for localised colon cancer, about two out of five patients will experience disease recurrence, but the most effective strategies for follow-up remain to be established. New drugs such as irinotecan, oxaliplatin and oral fluoropyrimidines may offer improved efficacy or patients' convenience in the adjuvant setting and their impact on survival will be evaluated in the recently closed large randomised studies. This review summarises the current status of adjuvant therapy in colon cancer and describes the future directions for research.

Antineoplastic Agents↗
PubMed2002

Chemotherapy in colorectal cancer: new options and new challenges.

Colorectal cancer is the second most common cause of cancer-related mortality in Europe and North America. Studies conducted in the last two decades have established the role of adjuvant therapy in stage III colon cancer. However, there is currently no international consensus with the role of adjuvant treatment in stage II disease. The introduction of irinotecan, oxaliplatin, oral fluoropyrimidines and raltitrexed has broadened the treatment options available for patients with advanced colorectal cancer. The integration of these drugs with the new molecular targeted therapies such as epidermal growth factor receptor, cyclooxygenase, angiogenesis and matrix metalloproteinase inhibition will form the basis of clinical research in the next few years and may, in the future, impact on the survival of patients with colorectal cancer. This review will focus on the place of chemotherapy in colorectal cancer, but not its role in combination with radiotherapy in rectal cancer.

Antimetabolites, Antineoplastic↗
PubMed2002

Gemcitabine and its combinations in the treatment of malignant lymphoma.

Although combination chemotherapy can induce complete remission in a large proportion of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL), 30%-50% of patients will relapse. Gemcitabine has shown promising activity in heavily pretreated patients with HD and NHL even in those who have progressed after autologous stem cell transplantation. Its favorable toxicity profile allows development of combination regimens with other cytotoxic drugs and anti-CD20-targeted therapy, although hematologic toxicities appear to be greater than when gemcitabine is used as a single agent. Prolonged infusion of gemcitabine at a pharmacologically guided dose rate of 10 mg/m2/minute has demonstrated a pharmacokinetic and pharmacodynamic advantage although clinical efficacy of prolonged infusion needs to be established. Thus far, gemcitabine has been mainly tested in relapsed or refractory patients, and its inclusion in front-line therapy may bring about greater benefit. However, as gemcitabine has not been evaluated in randomized studies either alone or in combination with other chemotherapy drugs, its exact role in the treatment paradigm of lymphoma remains to be determined.

Antibodies, Monoclonal↗