Biomedical subjects

A R Norman

Publications and source records attributed to A R Norman.

At least 19 recordsLinked to original sources

PubMed2006

Predictive poor prognostic factors in colonic carcinoma.

INTRODUCTION: Five-year survival in rectal cancer has been steadily improving since the introduction of neoadjuvant chemoradiation and total mesorectal excision surgery. In contrast, 5-year survival rates and management of colonic carcinoma remain relatively unchanged. This study aims to identify poor prognostic factors in colonic cancer patients that could potentially be predicted pre-operatively to identify a subset of patients amenable to neoadjuvant treatment strategies. METHODS: Database compilation of all operable rectal and colonic cancer patients presenting to a single district general hospital over 5 years. Data were documented on presentation and site of tumour, TNM staging, differentiation and extramural venous invasion. RESULTS: There was no significant difference in 4-year survival between rectal (57.5%) and right (57%) or left sided (52.5%) colonic cancers (p=0.4689). On multivariate analysis, N2-stage, T4-stage and emergency presentation were identified as independent prognostic factors. On univariate analysis, in addition to the above factors, presence of venous invasion (p=0.001) and poor differentiation (p=0.0003) of tumour also predicted for poor 5-year survival. CONCLUSION: T4-stage and N2-stage and extramural venous invasion are poor prognostic factors that could be identified pre-operatively with suitably accurate imaging. Such patients could then be considered for a pre-operative treatment strategy.

Adult↗

PubMed2006

Failure of dietetic referral in patients with gastrointestinal cancer and weight loss.

This study examined whether staff working within a cancer centre treating patients with gastrointestinal malignancy routinely identified individuals from outpatients for referral to a dietitian. A nutrition screening tool is employed only for in-patient admissions. Height, current and usual weight were recorded prospectively in all patients referred for consideration of treatment. First appointment with the dietitian, first hospital admission, demographic and clinical details were obtained from hospital records. Time from first appointment to referral to a dietitian was examined. Between September 2002 and March 2004, 920 patients were included. Five hundred and seventeen patients had lost weight, of whom 223 patients had lost between 5% and 10% and 294 patients had lost more than 10% of their pre-morbid weight. Three hundred and twenty-seven patients (36%) were referred to dietitians. Twenty eight (9%) of referrals were made by staff in outpatients. Two hundred and ninety-nine were referred during or after an inpatient admission but only 39% of these occurred within the first seven days following admission. One third of patients with more than 10% weight loss were not referred for dietary assessment, even following admission. The likelihood of referral was significantly associated with the degree of weight loss (univariate analysis hazard ratio (HR) 1.75, 95% Confidence Interval (CI) 1.4-2.19, multivariate HR 1.65, 95% CI 1.22-2.23) and was independent of factors such as performance status and clinical setting. Few patients were identified early in their treatment for referral to a dietitian. Since most chemotherapy is now given on an outpatient basis, patients are unlikely to be referred if they do not require admission. This study suggests that an out-patient dietetic screening tool is urgently required. Such screening is likely to result in considerable improvements to the clinical care of cancer patients with weight loss.

Aged↗

PubMed2006

Symptoms and weight loss in patients with gastrointestinal and lung cancer at presentation.

INTRODUCTION: Weight loss is an independent prognostic factor for decreased survival in cancer patients. The effectiveness of treatment is impaired in patients with weight loss. The aetiology of this weight loss is complex and poorly characterised. Decreased calorie intake may be important. The reasons for decreased intake are unknown. AIMS AND METHODS: To determine in adult patients with cancer, who had not started chemotherapy or radiotherapy, the prevalence of symptoms which carry a risk to nutritional status and how these relate to weight loss, tumour burden and primary tumour site. New patients referred for treatment of any form of gastrointestinal (GI) cancer, non-small cell lung cancer or lung mesothelioma completed a validated questionnaire recording symptoms contributing to weight loss (Patient-generated Subjective Global Assessment--PG-SGA). In a subset of patients without metastatic disease, computed tomography scans were assessed to determine tumour burden. RESULTS: Between August and October 2004, 122 patients with GI and 29 with lung cancers were recruited. There were 48% of GI and 28% of lung cancer patients who had lost weight. Sixty-two percent of the patients had one or more symptoms at presentation. The frequency of symptoms varied according to the site of disease. The most common symptom at all tumour sites was loss of appetite (38%). There was a weak but significant correlation between the number of symptoms and amount of weight loss (r=0.347). Patients reporting a reduced food intake had more symptoms than patients who had not lost weight. Tumour burden did not correlate with weight loss. CONCLUSION: The symptoms in cancer patients occur across different types of primary tumours, may affect food intake and have a part in causing weight loss. More information on the role of symptom management in improving nutritional status is needed.

Adult↗

PubMed2006

Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment of advanced pancreatic cancer: results from two randomised controlled trials.

Gastrin has been shown to be a growth stimulant in pancreatic cancer cells. Gastrazole is a potent and selective gastrin receptor antagonist. Two randomised blinded trials were conducted to assess the effect of gastrazole in advanced pancreatic cancer. Patients with biopsy-proven, inoperable pancreatic carcinoma were recruited. Trial A compared protracted venous infusion (PVI) gastrazole with PVI placebo, whereas trial B compared PVI gastrazole with PVI fluorouracil (5-FU). Eighteen patients were randomised in trial A. Gastrazole produced significantly better survival compared to placebo (median 7.9 months vs 4.5 months; 1-year survival: 33 vs 11%, respectively; log rank P=0.02). No difference in toxicity was seen between gastrazole and placebo, except central venous catheter and pump complications. Ninety-eight patients were randomised in trial B. No significant survival difference was detected between gastrazole and 5-FU (median: 3.6 vs 4.2 months; 1-year survival: 13.2 vs 26.2%, respectively; log rank P=0.42). Toxicity of gastrazole was mild with significantly less diarrhoea (P=0.03), stomatitis (P<0.001) and hand- foot syndrome (P<0.001) compared to 5-FU. Quality of life (QoL) assessment showed similar QoL between gastrazole and 5-FU at baseline and no significant differences occurred with treatment either between arms or within arms. Compared to placebo, patients with advanced pancreatic cancer treated with gastrazole appeared to live longer, albeit in a very small trial and will require confirmation with large-scale randomised data. However, it did not produce survival advantage over PVI 5-FU. Lack of toxicity for gastrazole may allow its combination with cytotoxic drugs.

Adult↗

PubMed2006

A phase 2 study of high-activity 186Re-HEDP with autologous peripheral blood stem cell transplant in progressive hormone-refractory prostate cancer metastatic to bone.

PURPOSE: We investigated the potential for improvement in disease control by use of autologous peripheral blood stem cell transplant (PBSCT) to permit administration of high activities of (186)Re-hydroxyethylidene diphosphonate (HEDP) in patients with progressive hormone-refractory prostate cancer (HRPC). METHODS: Eligible patients had progressive HRPC metastatic to bone, good performance status and minimal soft tissue disease. Patients received 5,000 MBq of (186)Re-HEDP i.v., followed 14 days later by PBSCT. Response was assessed using PSA, survival, pain scores and quality of life. RESULTS: Thirty-eight patients with a median age of 67 years (range 50-77) and a median PSA of 57 ng/ml (range 4-3,628) received a median activity of 4,978 MBq (186)Re-HEDP (range 4,770-5,100 MBq). The most serious toxicity was short-lived grade 3 thrombocytopenia in 8 (21%) patients. The median survival of the group is 21 months (95%CI 18-24 months) with Kaplan-Meier estimated 1- and 2-year survival rates of 83% and 40% respectively. Thirty-one patients (81%, 95% CI 66-90%) had stable or reduced PSA levels 3 months post therapy while 11 (29%, 95% CI 15-49%) had PSA reductions of >50% lasting >4 weeks. Quality of life measures were stable or improved in 27 (66%) at 3 months. CONCLUSION: We have shown that it is feasible and safe to deliver high-activity radioisotope therapy with PBSCT to men with metastatic HRPC. Response rates and survival data are encouraging; however, further research is needed to define optimal role of this treatment approach.

Aged↗

PubMed2006

MRI directed multidisciplinary team preoperative treatment strategy: the way to eliminate positive circumferential margins?

Histopathological audit of positive circumferential resection margins (CRMs) can be used as a surrogate measure of the success of rectal cancer treatment. We audited CRM involvement in rectal cancer patients and the impact of the multidisciplinary team (MDT) on implementing a magnetic resonance imaging (MRI)-based preoperative treatment strategy. Data were collected on all newly diagnosed rectal cancer patients treated in our network between January 1999 and December 2002. Data were analysed for MRI prediction and histopathological assessment of CRM together with the MDT meeting treatment decisions. The CRM+ve rate of those discussed at MDT vs those not discussed were compared. We re-audited the CRM+ve rates 1 year after introducing a policy of mandatory preoperative MRI-based MDT discussion. Of the 298 patients diagnosed with rectal cancer, 39 (13%) were deemed palliative, 178 underwent surgery alone and 81 underwent neoadjuvant therapy. Of these, 62 out of 178 patients underwent surgery alone without MRI-based MDT discussion resulting in positive CRM in 16 cases (26%) as compared to 1 out of 116 (1%) in those patients with MDT discussion of MRI. Overall CRM+ve rate in all nonpalliative patients with or without MDT discussion was 12.5% (32 out of 256), significantly lower than the <20% rate (P<0.001) quoted in national guidelines. Re-audit in 98 consecutive patients following a change of policy produced a lower CRM+ve rate of 3% (1 out of 37) for all surgery alone patients and an overall CRM+ve rate of 7% (5 out of 70). In conclusion, MDT discussion of MRI and implementation of a preoperative treatment strategy results in significantly reduced positive CRM in rectal cancer patients.

Adult↗

PubMed2006

Efficacy and tolerability of chemotherapy in elderly patients with advanced oesophago-gastric cancer: A pooled analysis of three clinical trials.

The aim of this study was to determine the benefits of chemotherapy for oesophago-gastric cancer (OGC) in patients 70 years and above (> or =70) in comparison to younger patients. 1080 patients were enrolled into three randomised controlled trials assessing fluorouracil-based combination chemotherapy. Patients received either a platinum-containing regimen (ECF, MCF), PVI 5-FU (protracted venous infusion of 5-fluorouracil)+/-mitomycin C (MMC), or FAMTX. Of the 1080 patients randomised, 257 (23.8%) were aged > or =70 years. There were no significant differences in the incidence of grades 3/4 toxicity between the two cohorts. Objective and symptomatic response rates, failure-free and overall survival were not significantly different. In a multivariate analysis, independent prognostic factors for survival were performance status and locally advanced disease, not age. Patients > or =70 years with OGC obtained similar benefits from palliative chemotherapy with respect to symptomatic response, tumour regression and survival, without increased toxicities.

Aged↗

PubMed2005

CA19-9 as a prognostic factor in inoperable pancreatic cancer: the implication for clinical trials.

In a multivariate analysis of 154 patients receiving chemotherapy, baseline CA19-9 was an independent prognostic factor for overall survival (OS) (HR 1.8; 95% CI: 1.3-2.5, P = 0.0004). The 1-year OS was 19 and 46%, respectively, for patients with a baseline CA19-9 above or below the median value. A fall of 20% in CA19-9 level from baseline was an independent prognostic factor for OS (HR 1.9; 95% CI: 1.1-3.4, P = 0.019).

Adult↗

PubMed2005

Capecitabine and mitomycin C as third-line therapy for patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan.

Protracted venous infusion 5-fluorouracil (5FU) combined with mitomycin C (MMC) has demonstrated significant activity against metastatic colorectal cancer. Owing to potential synergy based upon upregulation of thymidine phosphorylase by MMC, the combination of capecitabine and MMC may improve outcomes in irinotecan-refractory disease. Eligible patients with progressive disease during or within 6 months of second-line chemotherapy were treated with capecitabine (1250 mg m(-2) twice daily) days 1-14 every 3 weeks and MMC (7 mg m(-2) IV bolus) once every 6 weeks. A total of 36 patients were recruited, with a median age of 64 years (range 40-77), and 23 patients (78%) were performance status 0-1. The objective response rate was 15.2%. In all, 48.5% of patients had stable disease. Median failure-free survival was 5.4 months (95% CI 4.6-6.2). Median overall survival was 9.3 months (95% CI: 6.9-11.7). Grade 3 toxicities were palmar-plantar erythema 16.7%, vomiting 8.3%, diarrhoea 2.8%, anaemia 8.3%, and neutropenia 2.8%. No patients developed haemolytic uraemic syndrome. Symptomatic improvement occurred for pain, bowel symptoms, and dyspnoea. Capecitabine in combination with MMC is an effective regimen for metastatic colorectal cancer resistant to 5FU and irinotecan with an acceptable toxicity profile and a convenient administration schedule.

Adult↗

PubMed2005

Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF.

The purpose of the study was to establish the optimal dose of capecitabine (X) to be used within a multicentre, randomised study evaluating the potential roles of oxaliplatin (O) and X in chemonaive patients (pts) with advanced oesophagogastric cancer. Two by two design was used, and pts were randomised to one of four regimens and stratified for extent of disease, performance status (PS) and centre. The treatment regimens are epirubicin, cisplatin, 5-fluorouracil (ECF), EOF, ECX or EOX. Doses: E 50 mg m(-2), C 60 mg m(-2) and O 130 mg m(-2) i.v. 3 weekly; F 200 mg m(-2) day(-1) i.v. and X 500 mg m(-2) b.i.d.(-1) (escalated to 625 mg m(-2) b.i.d.(-1) after results of first interim analysis) p.o., continuously. First interim analysis was performed when 80 pts had been randomised. Dose-limiting fluoropyrimidine toxicities were stomatitis, palmar plantar erythema (PPE) and diarrhoea; 5.1% of X-treated pts experienced grade 3/4 toxicity. Protocol planned dose escalation of X to 625 mg m(-2) b.i.d.(-1) was instituted and a second interim analysis has been performed; results are presented in this paper. A total of 204 pts were randomised at the time of the protocol planned 2nd interim analysis. Grade 3/4 fluoropyrimidine-related toxicity was seen in 13.7% pts receiving F, 8.4% pts receiving X 500 mg m(-2) b.i.d.(-1) and 14.7% pts receiving X 625 mg m(-2) b.i.d.(-1). Combined complete and partial response rates were ECF 31% (95% CI 18.7-46.3), EOF 39% (95% CI 25.9-53.1), ECX 35% (95% CI 21.4-50.3), EOX 48% (95% CI 33.3-62.8). Grade 3/4 fluoropyrimidine toxicity affected 14.7% of pts treated with X 625 mg m(-2) b.i.d.(-1), which is similar to that observed with F, confirming this to be the optimal dose. The replacement of C by O and F by X does not appear to impair efficacy. The trial continues to total accrual of 1000 pts.

Administration, Oral↗

PubMed2005

Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer.

The purpose of this study was to determine whether epirubicin, cisplatin and infused 5FU (ECF) improves overall survival (OS) compared to 5FU, etoposide and leucovorin (FELV) in patients with previously untreated advanced biliary cancer in a prospective randomised study. Patients were randomly assigned to receive epirubicin, cisplatin and infused 5FU ECF or bolus 5FU etoposide and leucovorin (FELV). The primary end point was OS with secondary end points of objective response rate (ORR), failure-free survival (FFS), quality of life (QOL) and toxicity. In all, 54 patients were recruited with 27 randomly assigned to each arm. The median OS for ECF was 9.02 months (95% confidence interval (CI): 6.46-11.51) and FELV 12.03 months (95% CI: 9.3-14.7), P=0.2059. Objective response rates were similar for both arms: ECF 19.2% (95% CI: 6.55-39.3); FELV 15% (95% CI: 3.2-37.9), P=0.72. There was significantly increased grade 3/4 neutropenia with FELV vs ECF (53.8 vs 29.5%, respectively, P=0.020). Symptom resolution was impressive for both regimens. This is the largest reported randomised study to date in this setting. ECF did not improve OS compared to FELV, but was associated with less acute toxicity. These data suggest that chemotherapy can prolong OS and achieve good symptomatic relief in advanced biliary cancer.

Adult↗

PubMed2005

Distribution of mesorectal lymph nodes in rectal cancer: in vivo MR imaging compared with histopathological examination. Initial observations.

The aim of this work was to determine the distribution of mesorectal lymph nodes using T2-weighted magnetic resonance (MR) imaging compared with histopathological findings in patients with rectal carcinoma. Sixteen patients with rectal carcinoma undergoing primary surgery without pre-operative neoadjuvant treatment were evaluated using 3-mm axial T2-weighted MR imaging. The position of each visible mesorectal node on imaging was localised by measuring its minimum distance from the mesorectal fascia (d(m)), its minimum distance from the rectal wall (d(r)) and its distance from the distal tumour margin (d(v)). Independent assessment of d(m), d(r) and d(v) was made at histopathological examination. Eighty-five mesorectal nodes on in vivo MR imaging were matched to histopathological findings. On imaging, 67/85 mesorectal nodes were found at the level of the tumour and 84/85 were identified at or within 5 cm proximal to the tumour. Only one out of 85 nodes was seen below the inferior tumour margin. The mean difference of d(m) and d(r) obtained on in vivo MR imaging and histopathological examination was 0.7 mm (95% confidence interval, CI, -0.12 to 1.42 mm) and -1.1 mm (95% CI -2.29 to 0.14 mm), respectively. Almost all mesorectal nodes visible on MR imaging were found at the level of tumour or within 5 cm proximal to the tumour. This has implications for the planning of MR imaging and the level of mesorectal transection at surgery.

Adenocarcinoma↗

PubMed2005

Mucinous histology predicts for reduced fluorouracil responsiveness and survival in advanced colorectal cancer.

BACKGROUND: Mucinous carcinoma of the colon and rectum (mucinous CRC) is a histological subtype of colorectal adenocarcinoma for which there is little data on chemotherapy responsiveness. The purpose of this study was to investigate specifically the efficacy of fluorouracil-based first-line chemotherapy in patients with advanced mucinous CRC. PATIENTS AND METHODS: All patients with advanced mucinous CRC enrolled in three prospective randomized trials evaluating infused 5-fluorouracil as first-line treatment were compared with patients with non-mucinous subtypes enrolled in the same trials in a case-control study. Prognostic factors associated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. RESULTS: The study included 135 patients (45 cases and 90 controls). The response rates for cases and controls were 22% [95% confidence interval (CI), 11% to 38%] and 47% (95% CI, 36.1% to 58.2%), respectively (P=0.0058). Median OS for the mucinous CRC patients was 11.8 months (95% CI, 8.87-14.8) compared with 17.9 months (95% CI, 13.38-22.39) in the control group (univariate analysis, P=0.056); after correcting for significant prognostic factors by multivariate Cox regression analysis, P=0.0372 and hazard ratio (HR)=1.497 (1.02-2.19). CONCLUSION: Patients with advanced mucinous CRC have a poorer response to fluorouracil-based first-line chemotherapy and reduced survival compared with patients with non-mucinous CRC.

Adenocarcinoma, Mucinous↗

PubMed2005

Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma.

There is currently no standard salvage chemotherapy regimen in relapsed and refractory lymphoma. Gemcitabine is a novel nucleoside analogue, which acts synergistically with cisplatin both in vitro and in clinical studies. We evaluated the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) in 41 heavily pretreated patients with relapsed and refractory Hodgkin's and non-Hodgkin's lymphoma. The best-achieved response rate (RR) was 79% (95% CI 64-91), with a complete RR of 21%. In patients with chemo-resistant disease, the RR was 63%. Myelosuppression was the main toxicity, the incidence of Grade 3 or 4 anaemia, neutropenia and thrombocytopenia was 17.1, 61.0 and 53.7% respectively. Only one patient had neutropenic sepsis and none of the patients suffered from haemorrhage. Grade 3 or 4 nonhaematological toxicity was minimal and stem cell mobilisation was not inhibited. GEM-P is an effective salvage regimen and its use prior to autologous stem cell transplant warrants further investigation.

Adolescent↗

PubMed2005

A randomised comparison between 6 months of bolus fluorouracil/leucovorin and 12 weeks of protracted venous infusion fluorouracil as adjuvant treatment in colorectal cancer.

BACKGROUND: We performed a multicentre randomised trial to compare the efficacy and toxicity of 12 weeks of protracted venous infusion (PVI) 5-fluorouracil (5-FU) against the standard bolus monthly regimen of 5-FU/leucovorin (LV) given for 6 months as adjuvant treatment in colorectal cancer (CRC). PATIENTS AND METHODS: Patients with curatively resected stage II and III CRC were randomly assigned to 5-FU/LV [5-FU 425 mg/m(2) intravenously (i.v.) and LV 20 mg/m(2) i.v. bolus days 1-5 every 28 days for 6 months] or to PVI 5-FU (300 mg/m(2)/day for 12 weeks). RESULTS: Between 1993 and 2003, 801 eligible patients were randomised to 5-FU/LV (n=404) or PVI 5-FU (n=397). With a median follow-up of 5.3 years, 231 relapses and 220 deaths have been observed. Five-year relapse-free survival (RFS) was 66.7% [95% confidence interval (CI) 61.6% to 71.3%] and 73.3% (95% CI 68.4% to 77.6%) with bolus 5-FU/LV and PVI 5-FU, respectively [hazard ratio (HR) 0.8; 95% CI 0.62-1.04; P=0.10]. Five-year overall survival (OS) was 71.5% (95% CI 66.4% to 75.9%) and 75.7% (95% CI 70.8% to 79.9%) with bolus 5-FU/LV and PVI 5-FU, respectively (HR 0.79; 95% CI 0.61-1.03; P=0.083). There was a significant survival advantage for patients starting adjuvant chemotherapy within 8 weeks (P=0.044). Significantly less diarrhoea, stomatitis, nausea and vomiting, alopecia, lethargy, and neutropenia (all with P <0.0001) were seen with PVI 5-FU. CONCLUSIONS: There was no OS difference between the two arms, although PVI 5-FU was associated with a trend towards better RFS and OS compared with bolus 5-FU/LV, as well as significantly less toxicity. Based on our results, the probability of 12 weeks of PVI 5-FU being inferior to 6 months of bolus 5-FU/LV is extremely low (P <0.005), and therefore shorter duration of adjuvant treatment should be explored further.

Adult↗

PubMed2005

Tumour staging using magnetic resonance imaging in clinically localised prostate cancer: relationship to biochemical outcome after neo-adjuvant androgen deprivation and radical radiotherapy.

AIMS: To evaluate the prognostic significance of magnetic resonance imaging (MRI) tumour stage in clinically localised prostate cancer. MATERIALS AND METHODS: Between 1988 and 1999, 199 men with clinically localised prostate cancer (T -T4, N0/Nx, M0) were treated with neo-adjuvant androgen deprivation and radical radiotherapy, and were staged using MRI. Concordance between clinical tumour (cT) stage, as determined by digital rectal examination, and MRI tumour (mT) stage was assessed. Univariate and multivariate analyses using the Cox proportional hazards model were used to study the prognostic role of cT stage and mT stage in addition to established prognostic factors. RESULTS: Of these 199 patients, 103 (52%) were upstaged on MRI, seven (3%) were downstaged, and in 89 (45%) cT and mT stages were concordant. With median follow-up of 3.8 years, 5-year freedom from prostate-specific antigen (PSA) failure was 48% (95% confidence interval (CI) 39-56%). On univariate analysis, freedom from PSA failure was associated with mT stage (P = 0.009) as well as Gleason score (P < 0.001) and initial PSA (P < 0.001), but not cT stage (P = 0.449). On multivariate analysis, Gleason score (P = 0.001), initial PSA (P < 0.001), but not mT stage (P = 0.112) remained independent determinants of freedom from PSA failure. For the subgroup of 149 patients with cT1-2 disease, mT stage was a significant predictor of increased risk of PSA failure on univariate analysis (P = 0.005), but not multivariate analysis (P = 0.19). CONCLUSION: Freedom from PSA failure was more closely associated with mT stage than cT stage. Future studies are warranted to determine whether mT stage is an independent determinant of treatment outcome.

Aged↗

PubMed2005

Do serum levels of eosinophil granule-derived protein change in patients undergoing pelvic radiotherapy?

AIMS: Eosinophils have an important role in the pathogenesis of inflammatory bowel disease, with faecal levels of the eosinophil granule proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) reflecting disease activity. Eosinophil crypt abscesses are a characteristic histological finding in acute gastrointestinal radiation-induced mucosal damage. This pilot study aimed to investigate changes in serum levels of ECP/EPX during pelvic radiotherapy. MATERIALS AND METHODS: Patients with no history of inflammatory bowel disease, starting a 5-week course of pelvic radiotherapy, had serum ECP/EPX levels measured before radiotherapy and during the fourth week of treatment. Bowel toxicity was graded at week 4 using the Common Toxicity Criteria Scale. RESULTS: Fifteen patients who were to undergo adjuvant radiotherapy for gynaecological cancer were recruited. The mean serum levels of ECP and EPX before treatment were 17.3 microg/l (range 2.0-49.3 microg/l) and 37.3 microg/l (range 12.0-94.0 microg/l), respectively. The mean serum levels during week 4 of radiotherapy for ECP and EPX were 43.0 microg/l (range 2.4-164.0 microg/l) and 38.7 microg/l (range 9.0-79.0 microg/l), respectively. Serum ECP levels increased at week 4 compared with levels before radiotherapy (P = 0.02). Acute bowel toxicity was seen in 12 patients (80%) at week 4: Grade 1 in 25% patients and Grade 2 in 75%. In this small study, no correlation was seen between acute bowel toxicity at week 4 and serum ECP or EPX levels. CONCLUSIONS: Serum ECP levels increase in response to pelvic irradiation. This may reflect the known involvement of eosinophils in the acute response to radiotherapy. Further study is required to determine when levels start to rise and their relationship to the degree of acute bowel toxicity.

Aged↗

PubMed2004

Elderly patients with fluoropyrimidine and thymidylate synthase inhibitor-resistant advanced colorectal cancer derive similar benefit without excessive toxicity when treated with irinotecan monotherapy.

Elderly patients are recommended to have a reduced starting dose (300 mg m(-2) once every 3 weeks) of irinotecan monotherapy. The aims of this analysis are to compare toxicity and survival according to age, performance status (PS), gender and prior radical pelvic radiotherapy (RT). The primary end points were overall survival and an irinotecan-specific toxicity composite end point (TCE) defined as the occurrence of grade 3 or 4 diarrhoea, neutropenia, febrile neutropenia, fever, infection or nausea and vomiting. Between 1997 and 2003, 339 eligible patients with advanced colorectal cancer (CRC) progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospectively registered in a multicentre randomised trial. All patients commenced irinotecan at 350 mg m(-2) once every 3 weeks. There were no differences in proportions of patients developing TCE by age (<70 vs > or =70 : 37.8 vs 45.8%; P=0.218), PS (0-1 vs 2 : 39.3 vs 41.5%; P=0.793) or prior RT (RT vs no RT : 45.1 vs 38.5%; P=0.377). Males experienced more toxicity than females (44.3 vs 32.6%; P=0.031), but this was not significant after controlling for other co-variates (P=0.06). Patients aged > or =70 had similar objective responses (11.1 vs 9%; P=0.585) and survival (median 9.4 vs 9 months; log rank P=0.74) compared to younger patients. Elderly patients derive the same benefit without experiencing more toxicity with second-line irinotecan treatment for advanced CRC. Our data do not support the recommendation to reduce the starting dose for the elderly patients.

Adult↗