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Biomedical subjects

A Norman

Publications and source records attributed to A Norman.

At least 19 recordsLinked to original sources
PubMed2006

The role of intrathecal chemotherapy prophylaxis in patients with diffuse large B-cell lymphoma.

BACKGROUND: Relapse in the central nervous system (CNS) following initial treatment of diffuse large B-cell lymphoma (DLBCL) is an uncommon but serious complication. This single centre retrospective study investigated the rate of CNS relapse in patients with DLBCL who received standardised intrathecal (IT) chemoprophylaxis. PATIENTS AND METHODS: A total of 259 patients were newly diagnosed and treated for DLBCL from October 1996 to May 2005 and retrospectively analysed for incidence of CNS relapse. Our institutional policy for patients at risk for CNS relapse was for IT chemoprophylaxis to be administered concurrently with systemic treatment. Defined at-risk patients were those with lymphoma involvement at the following sites: bone marrow, testis, nasal/paranasal sinuses, orbits, bone/vertebrae and peripheral blood. RESULTS: Of 259 patients with DLBCL, a total of 51 patients (19.7%) received IT chemoprophylaxis. Forty-four patients received single agent IT methotrexate (MTX) 12.5 mg (median 3 doses, range 1-7); 27 patients (53%) received 1-3 doses and 17 patients (33.3%) 4-7 doses of MTX. Seven patients (13.7%) received a combination of IT MTX plus cytarabine. Three patients (1.1%) subsequently developed CNS relapse. One of these patients had IT chemoprophylaxis, the other two did not meet the Royal Marsden Hospital (RMH) criteria for IT chemoprophylaxis. The median time from diagnosis of DLBCL to CNS relapse was 31.8 months (range 27.3-34.1 months). CONCLUSION: The CNS relapse rate in this cohort of patients with primary DLBCL was low at 1.1%. This retrospective analysis demonstrates in a homogeneous group of DLBCL patients that a relatively low-intensity IT chemoprophylaxis regimen given according to site-based risk can be associated with a low risk of CNS relapse.

Adult↗
PubMed2006

Studies of uptake, elimination, and late effects in Atlantic salmon (Salmo salar) dietary exposed to Di-2-ethylhexyl phthalate (DEHP) during early life.

The phthalate esters are a group of industrial chemicals considered to have endocrine-disrupting properties. The most common tonnage product among these, di-2-ethylhexyl phthalate (DEHP), is widely spread in the environment. The objectives with the present work were to study uptake and metabolism of orally administered DEHP and its major metabolite mono-2-ethyl hexyl phthalate (MEHP) and to evaluate the impact of early life exposure on sex differentiation in Atlantic salmon. The feeding with contaminated diet started immediately after yolk sac resorption and continued for 4 weeks. Nominal concentrations of DEHP in the diet were 400 (measured 359), 800 (measured 827), and 1500 (measured 1648) mg DEHP/kg and a control group was fed food mixed with solvent. After the exposure period, fish were fed non-contaminated diet until final sampling 4 months post-exposure. There were no effects on growth or survival of the fish and no late effects on hepatosomatic index or sex ratio. However, the histological examination of gonads from fish exposed to 1500 mg DEHP/kg revealed a small but significant incidence (3%) of intersex fish (ovo-testis). Chemical residues of DEHP and MEHP were analyzed weekly during the first 3 months of the post-exposure period. Both DEHP and MEHP were rapidly eliminated to near background levels within one week post exposure. The study indicates that exposure of Atlantic salmon to relatively high concentrations of DEHP during a sensitive part of the life cycle may interfere with gonad differentiation.

Analysis of Variance↗
PubMed2006

Feasibility of familial PSA screening: psychosocial issues and screening adherence.

This study examined factors that predict psychological morbidity and screening adherence in first-degree relatives (FDRs) taking part in a familial PSA screening study. Prostate cancer patients (index cases - ICs) who gave consent for their FDRs to be contacted for a familial PSA screening study to contact their FDRs were also asked permission to invite these FDRs into a linked psychosocial study. Participants were assessed on measures of psychological morbidity (including the General Health Questionnaire; Cancer Worry Scale; Health Anxiety Questionnaire; Impact of Events Scale); and perceived benefits and barriers, knowledge; perceived risk/susceptibility; family history; and socio-demographics. Of 255 ICs, 155 (61%) consented to their FDRs being contacted. Of 207 FDRs approached, 128 (62%) consented and completed questionnaires. Multivariate logistic regression revealed that health anxiety, perceived risk and subjective stress predicted higher cancer worry (P = 0.05). Measures of psychological morbidity did not predict screening adherence. Only past screening behaviour reliably predicted adherence to familial screening (P = 0.05). First-degree relatives entering the linked familial PSA screening programme do not, in general, have high levels of psychological morbidity. However, a small number of men exhibited psychological distress.

Aged↗
PubMed2006

Evaluating the effect of reducing the high-dose volume on the toxicity of radiotherapy in the treatment of bladder cancer.

AIMS: The radiation dose used to treat bladder cancer is limited by the risk of inducing severe late bladder toxicity. Retrospective data suggest that radiation tolerance is greater for partial rather than whole bladder irradiation. Limiting the high-dose region to a section of the bladder may reduce toxicity, opening the way for dose escalation. The aims of this study were to establish the efficacy and compare the late toxicity between (1) a two-phase technique limiting the high-dose area and (2) a conventional single-phase radiotherapy to the whole bladder. MATERIALS AND METHODS: A cohort study was undertaken of 229 patients with invasive bladder cancer treated with computed tomography-planned radical radiotherapy at the Royal Marsden Hospital from 1984 to 1998. In total, 154 patients received a single-phase treatment to the whole bladder with a 2 cm margin. Seventy-five patients with solitary, well-localised tumours were selected for treatment using a two-phase technique. The first phase (12 Gy) aimed to treat the tumour with a 2 cm margin. A second phase treated the whole bladder with 52 Gy. One hundred and forty-one patients were planned to receive a dose of 60-64 Gy/30-32 fractions over 6-6.5 weeks, whereas 88 patients received an accelerated regime. Data on late bladder and bowel toxicity (using Radiation Therapy Oncology Group criteria) were collected prospectively at the annual review. RESULTS: At the 5-year follow-up there was no difference in overall survival (hazard ratio = 0.91, 95% confidence interval 0.64-1.3) or failure-free survival (hazard ratio = 1.02, 95% confidence interval 0.73-1.43) between the two techniques. The two-phase reduced volume treatment was less toxic, with a 19% absolute reduction in overall grade 3-4 late toxicity (P = 0.02). These differences were more marked for bladder toxicity compared with bowel toxicity. CONCLUSIONS: The two-phase reduced volume technique was associated with less bladder and bowel toxicity than conventional whole bladder radiotherapy without evidence of impaired survival.

Cohort Studies↗
PubMed2006

Exonic STK11 deletions are not a rare cause of Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant cancer predisposition syndrome characterised by oro-facial pigmentation and hamartomatous polyposis of the gastrointestinal tract. A causal germline mutation in STK11 can be identified in 30% to 80% of PJS patients. METHODS: Here we report the comprehensive mutational analysis of STK11 in 38 PJS probands applying conventional PCR based mutation detection methods and the recently introduced MLPA (multiplex ligation dependent probe amplification) technique developed for the identification of exonic deletions/duplications. RESULTS: Nineteen of 38 probands (50%) had detectable point mutations or small scale deletions/insertions and six probands (16%) had genomic deletions encompassing one or more STK11 exons. CONCLUSIONS: These findings demonstrate that exonic STK11 deletions are a common cause of PJS and provide a strong rationale for conducting a primary screen for such mutations in patients.

AMP-Activated Protein Kinase Kinases↗
PubMed2005

Is supplementation with elemental diet feasible in patients undergoing pelvic radiotherapy?

BACKGROUND: Acute gastrointestinal upset occurs in approximately 80% of patients undergoing radiotherapy for pelvic cancers. Underlying changes relate to denudation of the mucosal layer which renders the small intestine vulnerable to additional damage from proteolytic enzymes and bile acids. Severe acute bowel symptoms may predispose to progressive fibrotic and ischaemic changes. Elemental diet given during treatment may reduce acute and chronic bowel symptoms induced by pelvic radiotherapy. METHODS: This study aimed to assess compliance with elemental diet during pelvic radiotherapy. Patients with gynaecological, urological or rectal malignancy undergoing radical or adjuvant pelvic radiotherapy were randomised to one of five groups. Each group was assigned a target quantity of three different elemental sip feeds (Group 1, 20%, Group 2, 50%, Group 3, 75% of calorie requirements taken as E028 extra liquid; Group 4, 50% of calorie requirements taken as E028 extra powder; Group 5, 50% of calorie requirements taken as Emsogen powder). Compliance was assessed using a diary card and weekly assessment. Statistical analyses were conducted on an intention to treat basis. RESULTS: Fifty patients (44 female, six male) mean age 58 yr (95% CI 55-61), were recruited to the study (24 endometrial, 17 cervical, 7 rectal, 1 vulval and 1 bladder carcinoma). Mean weight at baseline was 74.5 kg (95% CI 69-80) and this did not change during treatment. Full compliance was achieved in three patients, all from Group 1. By week 5, only 46% of patients were consuming elemental diet. Post hoc analysis of variance with repeated measures indicated that there were no significant differences in volume of elemental diet consumed between groups (P = 0.937). There was a significant inverse linear relationship between intake of elemental diet and time (P < 0.001). CONCLUSIONS: Different formulations of elemental diet do not influence compliance. Patients are unlikely to be able to consume more than one-third of their calorie requirements in the form of an elemental sip feed. Further investigation is warranted to determine if intervention with this volume of elemental diet is beneficial.

Analysis of Variance↗
PubMed2005

Fertility, gonadal and sexual function in survivors of testicular cancer.

Modern treatments cure most testicular cancer patients, so an important goal is to minimise toxicity. Fertility and sexual functioning are key issues for patients. We have evaluated these outcomes in a cross-sectional study of long-term survivors of testicular cancer. In total, 680 patients treated between 1982 and 1992 completed the EORTC Qly-C-30(qc30) questionnaire, the associated testicular cancer specific module and a general health and fertility questionnaire. Patients have been subdivided according to treatment received: orchidectomy either alone (surveillance, S n = 169), with chemotherapy (C, n = 272), radiotherapy (R, n = 158), or both chemotherapy and radiotherapy (C/RT n = 81). In the surveillance group, 6% of patients had an elevated LH, 41% an elevated FSH and 11% a low (< 10 nmol l(-1)) testosterone. Hormonal function deteriorated with additional treatment, but the effect in general was small. Low testosterone was more common in the C/RT group (37% P = 0.006), FSH abnormalities were more common after chemotherapy (C 49%, C/RT 71% both P < 0.005) and LH abnormalities after radiotherapy (11% P < 0.01) and chemotherapy (10%, P < 0.001). Baseline hormone data were available for 367 patients. After treatment, compared to baseline, patients receiving chemotherapy had significantly greater elevations of FSH (median rise of 6 (IQR 3-9.25) iu l(-1) compared to 3 (IQR 1-5) iu l(-1) for S; P < 0.001) and a fall (compared to a rise in the surveillance group) in median testosterone levels (-2 (IQR -8.0 to -1.5) vs 1.0. (IQR -4.0-4.0) P < 0.001). Patients with low testosterone (but not elevated FSH) had lower quality of life scores related to sexual functioning on the testicular cancer specific module and lower physical, social and role functioning on the EORTC Qly C-30. Patients with a low testosterone also had higher body mass index and blood pressure. Treatment was associated with reduction in sexual activity and patients receiving chemotherapy had more concerns about fathering children. In total, 207 (30%) patients reported attempting conception of whom 159 (77%) were successful and a further 10 patients were successful after infertility treatment with an overall success rate of 82%. There was a lower overall success rate after chemotherapy (C 71%; CRT 67% compared to S 85% (P = 0.028)). Elevated FSH levels were associated with reduced fertility (normal FSH 91% vs elevated 68% P < 0.001). In summary, gonadal dysfunction is common in patients with a history of testicular cancer even when managed by orchidectomy alone. Treatment with chemotherapy in particular can result in additional impairment. Gonadal dysfunction reduces quality of life and has an adverse effect on patient health. Most patients retain their fertility, but the risk of infertility is likely to be increased by chemotherapy. Screening for gonadal dysfunction should be considered in the follow-up of testicular cancer survivors.

Adolescent↗
PubMed2005

A modified Inflammatory Bowel Disease questionnaire and the Vaizey Incontinence questionnaire are simple ways to identify patients with significant gastrointestinal symptoms after pelvic radiotherapy.

After radiotherapy for pelvic cancer, chronic gastrointestinal problems may affect quality of life (QOL) in 6-78% of patients. This variation may be due to true differences in outcome in different diseases, and may also represent the inadequacy of the scales used to measure radiotherapy-induced gastrointestinal side effects. The aim of this study was to assess whether outcome measures used for nonmalignant gastrointestinal disease are useful to detect gastrointestinal morbidity after radiotherapy. Results obtained from a Vaizey Incontinence questionnaire and a modified Inflammatory Bowel Disease questionnaire (IBDQ)--both patient completed--were compared to those from a staff administered Late Effects on Normal Tissue (LENT)--Subjective, Objective, Management and Analytic (SOMA) questionnaire in patients who had completed radiotherapy for a pelvic tumour at least 3 months previously. In all, 142 consecutive patients were recruited, 72 male and 70 female, median age 66 years (range 26-90 years), a median of 27 (range 3-258) months after radiotherapy. In total, 62 had been treated for a gynaecological, 58, a urological and 22, a gastrointestinal tract tumour. Of these, 21 had undergone previous gastrointestinal surgery and seven suffered chronic gastrointestinal disorders preceding their diagnosis of cancer. The Vaizey questionnaire suggested that 27% patients were incontinent for solid stools, 35% for liquid stools and 37% could not defer defaecation for 15 min. The IBDQ suggested that 89% had developed a chronic change in bowel habit and this change significantly affected 49% patients: 44% had more frequent or looser bowel movements, 30% were troubled by abdominal pain, 30% were troubled by bloating, 28% complained of tenesmus, 27% were troubled by their accidental soiling and 20% had rectal bleeding. At least 34% suffered emotional distress and 22% impairment of social function because of their bowels. The small intestine/colon SOMA median score was 0.1538 (range 0-1) and the rectal SOMA median score was 0.1428 (range 0-1). Pearson's correlations for the IBDQ score and small intestine/colon SOMA score was -0.630 (P<0.001), IBDQ and rectum SOMA -0.616 (P<0.001), IBDQ and Vaizey scores -0.599 (P<0.001), Vaizey and small intestine/colon SOMA 0.452 (P<0.001) and Vaizey and rectum SOMA 0.760 (P<0.001). After radiotherapy for a tumour in the pelvis, half of all patients develop gastrointestinal morbidity, which affects their QOL. A modified IBDQ and Vaizey questionnaire are reliable in assessing new gastrointestinal symptoms as well as overall QOL and are much easier to use than LENT SOMA.

Adult↗
PubMed2005

The utility of digital rectal examination after radical radiotherapy for prostate cancer.

AIMS: The aim of the current study was to determine the utility of routine digital rectal examination (DRE) after radical radiotherapy for prostate cancer. MATERIALS AND METHODS: Between 1990 and 1999, 899 patients with clinically localised prostatic adenocarcinoma (T1-4, N0/Nx, M0/Mx) underwent neoadjuvant androgen deprivation and radical radiotherapy at the Royal Marsden Hospital. Patients were followed with serum prostate-specific antigen (PSA) test and DRE carried out at 6-monthly intervals for the first 2 years, and then annually. RESULTS: At a median follow-up of 5 years, 39 out of 899 cases (4.3%) had local recurrence detected on DRE. DRE failed to detect any local recurrences in the absence of a rising PSA. The lowest serum PSA concentration at the time of clinically detectable local recurrence was 1.7 ng/ml. CONCLUSIONS: These findings question the standard model of follow-up after radiotherapy for prostate cancer, and suggest that alternatives, such as telephone clinics, should be considered.

Adenocarcinoma↗
PubMed2004

Chemotherapy for primary gastric lymphoma: does in-patient observation prevent complications?

AIMS: Primary gastric lymphoma (PGL) is the most common site of extra-nodal non-Hodgkin's lymphoma (NHL). In recent years there has been a move away from a surgical approach to primary chemotherapy with or without radiotherapy. Data support this approach, with overall survival rates equivalent or superior to surgery. Concerns have been raised over the incidence of acute chemotherapy complications, primarily gastrointestinal (GI) haemorrhage and perforation. As a result, several units, including our own, have routinely admitted all patients for observation during the commencement of therapy. We conducted an audit to elucidate the incidence and timing of such complications. MATERIALS AND METHODS: We used our prospectively recorded lymphoma database to identify all patients with aggressive PGL treated with primary chemotherapy. We examined individual patient notes for the incidence of gastric perforation and GI haemorrhage, defined as a fall in haemoglobin of least 2 g/dl, or the occurrence of haematemesis or malaena. RESULTS: We identified 29 patients with aggressive PGL who received primary systemic chemotherapy. Of these, only two had acute complications, one with GI bleed and the other with perforation. Both events occurred after discharge following our standard inpatient admission period of 5 days (day 13 and day 17). CONCLUSION: In this study, the rate of acute chemotherapy-related complications is low (6.9%). This is consistent with most published series, in which the incidence seems to be around 5% or less. Both acute complications in this series occurred after the patients had been discharged following a routine admission period of 5 days for observation. Although rarely documented, other series suggest that these events also occur late after the initiation of chemotherapy. This work suggests that routine admission for the initiation of chemotherapy for PGL is not necessary and should be at the discretion of the treating physician. All patients should receive comprehensive education about the risks and clinical signs of gastric perforation and bleed. This change in policy has obvious implications for healthcare resources.

Adult↗
PubMed2003

Cardiovascular disease as a long-term complication of treatment for testicular cancer.

PURPOSE: To assess the risk of cardiovascular morbidity and cardiac risk factors in long-term survivors of testicular cancer according to treatment received. PATIENTS AND METHODS: All resident male patients registered in the United Kingdom between 1982 and 1992 attending for follow-up were eligible for recruitment. Patients completed a current health questionnaire and underwent clinical review, along with hematologic, biochemical, and hormonal profiles. For patients not under routine review, follow-up information was sought from their general practitioner and mortality data were sought from the Office of National Statistics. Descriptive analysis was performed on all variables and comparisons were made among patients treated by orchidectomy and follow-up only, chemotherapy alone (C), radiotherapy alone (RT), and radiotherapy and chemotherapy (C/RT). RESULTS: Data on cardiovascular events were available on 992 patients. After a median follow-up of 10.2 years, 68 events had been reported, including 18 deaths. After adjusting for age, increased risk for cardiac events was seen after C (relative risk [RR] = 2.59; 95% confidence interval [CI], 1.15 to 5.84; P =.022), RT (RR = 2.40; 95% CI, 1.04 to 5.45; P =.036), and C/RT (RR = 2.78; 95% CI, 1.09 to 7.07; P =.032). There were no significant differences in cardiac risk factors. On multivariate analysis, age, treatment group, free thyroxine, protein, and magnesium levels were associated with cardiovascular disease. CONCLUSION: In long-term survivors of testicular cancer, we observed a two-fold or greater risk of developing cardiovascular disease. This was not due to increases in cardiac risk factors, which suggests a direct or indirect treatment effect. These data support the continued research into the minimization of treatment in good-prognosis testicular cancer.

Adult↗
PubMed2003

Intensive induction chemotherapy with CBOP/BEP in patients with poor prognosis germ cell tumors.

PURPOSE: Despite a high cure rate in patients with testicular cancer, there remain patients in the poor prognosis group who have a less favorable outcome. Intensive induction chemotherapy using a regimen consisting of carboplatin, bleomycin, vincristine, and cisplatin, followed by bleomycin, etoposide, and cisplatin (CBOP/BEP), developed at the Royal Marsden Hospital, is designed to overcome the rapid proliferation seen in germ cell tumors. This study assesses the outcome of patients with poor-prognosis nonseminomatous germ cell tumors (NSGCT) treated with CBOP/BEP. PATIENTS AND METHODS: Patients with NSGCT from three centers, classified as poor prognosis according to International Germ Cell Classification Consensus Group criteria, were treated with CBOP/BEP regimen during the period from 1989 to 2000. Data on treatment toxicity, relapse-free survival (RFS), and overall survival (OS) were collected prospectively on a hospital database. RESULTS: Fifty-four male patients with poor prognosis NSGCT were treated with CBOP/BEP. The RFS at 3 and 5 years for all patients was 83.2% (95% confidence interval [CI], 68.8% to 91.3%). After a median follow-up of 4 years, the OS of the 54 patients was 91.5% (95% CI, 78.6% to 96.8%) at 3 years and 87.6% (95% CI, 71.3% to 94.9%) at 5 years. Three-year OS in patients with a primary mediastinal germ cell tumor was 77.1% (95% CI, 34.5% to 93.9%) compared with 95.4% (95% CI, 82.8% to 98.8%) in patients with a testicular primary tumor (P =.24). CONCLUSION: The results reported here compare favorably with the historical results of alternative regimens used in the management of poor-prognosis NSGCT. We suggest a phase III trial to confirm our findings.

Adolescent↗
PubMed2003

Severe hypophosphatasia: characterization of fifteen novel mutations in the ALPL gene.

Hypophosphatasia is an inherited disorder characterized by defective bone mineralization and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. We report the characterization of ALPL gene mutations in a series of 11 families from various origins affected by perinatal and infantile hypophosphatasia. Sixteen distinct mutations were found, fifteen of them not previously reported: M45V, G46R, 388-391delGTAA, 389delT, T131I, G145S, D172E, 662delG, G203A, R255L, 876-881delAGGGGA, 962delG, E294K, E435K, and A451T. This confirms that severe hypophosphatasia is due to a large spectrum of mutations in Caucasian populations.

Alkaline Phosphatase↗
PubMed2003

Mitomycin C, carboplatin and protracted venous infusion 5-fluorouracil in advanced oesophago-gastric and pancreatic cancer: results of two phase II studies.

Cisplatin is an active palliative chemotherapy agent in advanced upper gastrointestinal cancer, but it is associated with significant non-haematological toxicity. Substitution of cisplatin by carboplatin in combination chemotherapy regimens may reduce these adverse effects. These two phase II studies evaluated the efficacy and toxicity of the combination of mitomycin C (MMC) 7 mg/m2 q 6 weekly, carboplatin area under the concentration-time curve 5 mg/ml/min q 3 weekly and protracted venous infusion 5-fluorouracil (5FU) 300 mg/m2/day (McarboF) in advanced upper gastrointestinal cancer. Between October 1998 and June 2000, 31 patients were enrolled in the studies, 23 patients in the oesophago-gastric study and eight patients in the pancreatic study. Although non-haematological toxicity was modest, both protocols were closed prematurely because of excessive haematological toxicity and frequent treatment delays. The overall incidence of grade 3/4 neutropenia and thrombocytopenia was 39 and 52%, respectively. The McarboF combination showed significant activity with an overall response rate of 52% in advanced oesophago-gastric cancer. Palliative benefit was also evident with improvement in symptoms of pain and weight loss in over 79 and 50% of patients in the oesophago-gastric study and pancreatic study, respectively. Median overall survival times were 10.6 and 6.6 months for patients with oesophago-gastric and pancreatic cancer, respectively. The McarboF regimen showed promising activity in advanced upper gastrointestinal cancer, with modest non-haematological side-effects. This combination merits further evaluation with modification of the dose and schedule of carboplatin and MMC in order to reduce the severity of haematological toxicity.

Adult↗
PubMed2003

The role of surveillance CT scans in patients with diffuse large B-cell non-Hodgkin's lymphoma.

The use of routine surveillance computed tomography (CT) scans in the follow-up of patients with diffuse large B-cell lymphoma may allow the detection of early asymptomatic relapse. On this basis, CT scans are frequently included in follow-up schedules, but the utility of this investigation in this setting has never been determined. This study evaluated the effectiveness of routine surveillance CT scans performed 3 and 12 months after completion of chemotherapy in patients with diffuse large B-cell lymphoma who had achieved a complete response. One hundred and seventeen patients with diffuse large B-cell lymphoma achieved complete remission at the Royal Marsden Hospital using first line combination chemotherapy between January 1992 and January 2000. The median follow-up was 4.6 years and 35 patients subsequently relapsed. Relapse was associated with the development of new symptoms and/or signs in 86% of cases. Only 5.7% of relapses were detected in asymptomatic patients using surveillance CT scans. Routine surveillance CT scans are of limited value in detecting asymptomatic early relapse and other approaches are required in order to identify patients destined to relapse at an earlier stage.

Adolescent↗
PubMed2002

Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer.

PURPOSE: We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) (ECF) with the combination of mitomycin, cisplatin, and PVI 5-FU (MCF) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS: Five hundred eighty patients with adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma were randomized to receive either ECF (epirubicin 50 mg/m(2) every 3 weeks, cisplatin 60 mg/m(2) every 3 weeks and PVI 5-FU 200 mg/m(2)/d) or MCF (mitomycin 7 mg/m(2) every 6 weeks, cisplatin 60 mg/m(2) every 3 weeks, and PVI 5-FU 300 mg/m(2)/d) and analyzed for survival, response, toxicity, and quality of life (QOL). RESULTS: The overall response rate was 42.4% (95% confidence interval [CI], 37% to 48%) with ECF and 44.1% (95% CI, 38% to 50%) with MCF (P =.692). Toxicity was tolerable, and there were only two toxic deaths. ECF resulted in more grade 3/4 neutropenia and grade 2 alopecia, but MCF caused more thrombocytopenia and plantar-palmar erythema. Median survival was 9.4 months with ECF and 8.7 months with MCF (P =.315); at 1 year, 40.2% (95% CI, 34% to 46%) of ECF and 32.7% (95% CI, 27% to 38%) of MCF patients were alive. Median failure-free survival was 7 months with both regimens. Global QOL scores were better with ECF at 3 and 6 months. CONCLUSION: This study confirms response, survival, and QOL benefits of ECF observed in a previous randomized study. The equivalent efficacy of MCF was demonstrated, but QOL was superior with ECF. ECF remains one of the reference treatments for advanced esophagogastric cancer.

Adult↗
PubMed2002

Occupational physical activity and risk for prostate cancer in a nationwide cohort study in Sweden.

We investigated effects of occupational physical activity on relative risk for prostate cancer. From Swedish nationwide censuses in 1960 and 1970, we defined two cohorts of men whose occupational titles allowed classification of physical activity levels at work in 1960 (n=1,348,971) and in 1970 (n=1,377,629). A third cohort included only men whose jobs required a similar level of physical activity in both 1960 and 1970 (n=673,443). The incidence of prostate cancer between 1971 and 1989 was ascertained through record linkage to the Swedish Cancer Register. A total of 43,836, 28,702, and 19,670 prostate cancers, respectively, occurred in the three cohorts. In all three cohorts, the relative risk for prostate cancer increased with decreasing level of occupational physical activity (P<0.001), using Poisson regression. Among men with the same physical activity levels in 1960 and 1970, the rate ratio was 1.11 for men with sedentary jobs as compared with those whose jobs had very high/high activity levels after adjustment for age at follow-up, calendar year of follow-up and place of residence (95% CI 1.05-1.17; P for trend <0.001). There was no association between occupational activity and prostate cancer mortality. Since we had no data on other potential risk factors the observed associations for both incidence and mortality might have been confounded. Further studies are needed to better understand the potential role of physical activity for prostate cancer.

Adult↗