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Biomedical subjects

R D James

Publications and source records attributed to R D James.

At least 19 recordsLinked to original sources
PubMed2006

Preoperative radiotherapy for operable rectal cancer--is a lower dose to a reduced volume acceptable?

AIMS: A retrospective audit was carried out to determine the rate of local recurrence (recurrent tumour within the lesser pelvis or the perineal wound) in 88 rectal cancer patients treated with 20 Gy/four fractions of adjuvant preoperative radiotherapy and curative surgery. MATERIALS AND METHODS: All patients were followed-up by clinical examination with rigid sigmoidoscopy at 6 monthly intervals if the rectum was intact, and computed tomography of the pelvis at 1, 2 and 5 years after surgery. In total, 171 patients with rectal cancer were identified under the care of one surgeon over a period of 11 years from May 1992 to April 2003. We excluded patients with rectal cancer from preoperative adjuvant radiotherapy if they had evidence at presentation of distant metastases, if they had fixed rectal tumours, were treated by local excision and had previous radiotherapy to the pelvis. On this basis, only 88 were considered for preoperative radiotherapy and curative resection with a median follow-up of 5.16 years. RESULTS: The 5-year survival by stage was Dukes A 96%, Dukes B 65% and Dukes C 36%. Overall, four patients (of 88) developed a recurrence within the lesser pelvis or the perineal wound, giving a local recurrence of 4.2% at 3 years (from a Kaplan-Meier graph). CONCLUSIONS: This single-centre audit suggests that a lower dose of radiotherapy to a smaller volume provides an acceptable local recurrence rate that compares very favourably with the well-publicised Swedish and Dutch trials of 25 Gy/five fractions. It was not the intention of this audit to suggest that this dose should be widely adopted. However, given the long-term gastrointestinal morbidity and risk of second malignancies, we advise caution when formulating even more intensive radiotherapy and chemoradiotherapy regimens for rectal cancer.

Adenocarcinoma↗
PubMed2004

Limited field radiotherapy for early stage, infra-diaphragmatic Hodgkin's lymphoma.

AIMS: To analyse the treatment outcome for patients with stage I and II infra-diaphragmatic Hodgkin's lymphoma. MATERIALS AND METHODS: A retrospective review of case notes for 33 consecutive patients treated between 1988 and 2000. Twenty-five out of 33 patients received radiotherapy alone, three out of 33 patients received minimal initial chemotherapy (MIT) (4 weeks VAPEC B) and five patients received six cycles of ChlVPP EVA hybrid chemotherapy before radiotherapy. Radiotherapy was given as a limited field in 32 out of 33 patients. RESULTS: Twenty-seven out of 33 patients were men (82%), and the median age was 47 years. Fifteen of the 33 patients were stage IA, 15 were IIA, 1 was IB and 2 were IIB. The median follow-up was 71 months. Histological subtype was lymphocyte predominant (15/33), nodular sclerosis (11/33), mixed cellularity (4/33), lymphocyte-rich classical (1/33) and unclassifiable (2/33). The 5-year overall survival was 89% and 5-year relapse-free survival was 85%. The median time to relapse was 37 months (range 7-65 months). One out of five relapses was within the previous radiotherapy field. All five relapses had received radiotherapy alone and four were salvaged with chemotherapy. There have been four second malignancies and one patient transformed to high-grade non-Hodgkin's lymphoma. No patient has died of Hodgkin's lymphoma. CONCLUSIONS: In our cohort of patients with infra-diaphragmatic stage I and II Hodgkin's lymphoma treated with limited-field radiotherapy, no patients died from uncontrolled disease. The use of MIT may reduce the risk of relapse and obviate the need for conventional salvage chemotherapy. Late relapses may occur, and second malignancies are a cause for concern underlining the need for long-term follow-up.

Adult↗
PubMed2003

Comparison of intermittent and continuous palliative chemotherapy for advanced colorectal cancer: a multicentre randomised trial.

BACKGROUND: Policies of UK clinicians regarding the duration of chemotherapy for patients with advanced colorectal cancer are not consistent. We aimed to compare effectiveness of continuous and intermittent chemotherapy in such patients. METHODS: Patients who responded or had stable disease after receiving 12 weeks of the regimens described by de Gramont and Lokich, or raltitrexed chemotherapy, were randomised to either intermittent (a break in chemotherapy, re-starting on the same drug on progression), or continuous chemotherapy until progression. FINDINGS: 354 patients (178 intermittent, 176 continuous) were enrolled from 42 UK centres. At randomisation, 41% of participants had part or complete response; 59% were stable. Only 66 (37%) patients allocated to intermittent treatment restarted as planned, after a median of 130 days. Median time on treatment after restarting was 84 days. Patients in the continuous group remained on treatment for a median of a further 92 days. Similar proportions of patients in both groups received second-line therapy. Patients on intermittent chemotherapy had significantly fewer toxic effects and serious adverse events than those in the continuous group. There was no clear evidence of a difference in overall survival (hazard ratio 0.87 favouring intermittent, 95% CI 0.69-1.09, p=0.23). INTERPRETATION: Our findings provided no clear evidence of a benefit in continuing therapy indefinitely until disease progression. They showed that it is safe to stop chemotherapy after 12 weeks and re-start the same treatment on progression in patients with chemosensitive advanced colorectal cancer.

Adult↗
PubMed2003

Randomized clinical trial of adjuvant radiotherapy and 5-fluorouracil infusion in colorectal cancer (AXIS).

BACKGROUND: Postoperative portal vein infusion (PVI) of 5-fluorouracil (5-FU) is a well tolerated and widely applicable treatment for colorectal cancer that might have an enormous public health impact, even if it produced survival benefits of just a few per cent. Very large trials are required to detect such differences, and the Adjuvant X-ray and 5-FU Infusion Study (AXIS) is the largest such trial yet reported. METHODS: Consenting patients with presumed colorectal cancer were randomized to surgery with or without 7 days of PVI (1 g 5-FU plus 5000 units heparin in 1 litre 5 per cent dextrose infused over each 24-h period). In addition, patients with rectal cancer could be randomized to radiotherapy or no radiotherapy to be given either before or after surgery. RESULTS: Between November 1989 and December 1997, 3583 patients were randomized with respect to PVI. The survival hazard ratios (95 per cent confidence interval (c.i.)) in all patients randomized and in the curatively resected subgroup (71.2 per cent of patients) were 1.00 (0.92 to 1.11) and 0.94 (0.83 to 1.06) respectively. Tests for heterogeneity suggested a greater treatment benefit for patients with colonic cancer than for patients with rectal cancer with respect to disease-free survival (hazard ratio 0.79 versus 1.03; P = 0.07), and there was a non-significant trend with respect to overall survival (hazard ratio 0.87 versus 1.03; P = 0.17). No survival benefit was seen in the 761 patients randomized with respect to radiotherapy; although not statistically significant, the impact on local recurrence rates was similar to that reported in the literature. CONCLUSION: No overall benefit of PVI was established in AXIS when colonic and rectal cancers were considered together, but the evidence suggesting a differential treatment effect according to site of cancer in AXIS was strongly supported by a meta-analysis incorporating the previous trials. Combining the data gave hazard ratios of 0.82 and 1.00 for colonic and rectal tumours respectively (test for interaction, P = 0.024), equating to an absolute survival benefit for patients with colonic cancer of 5.8 (95 per cent c.i. 2.8 to 8.5) per cent, a level close to that seen for prolonged systemic therapy.

Adult↗
PubMed2003

Raltitrexed plus radiotherapy for the treatment of unresectable/recurrent rectal cancer: a phase I study.

BACKGROUND: Current consensus is that a combination of radiotherapy and chemotherapy may provide the optimal treatment for patients with unresectable rectal cancer. Raltitrexed has proven efficacy in the treatment of advanced colorectal cancer and has an acceptable toxicity profile. The aim of this phase I study was to determine the recommended dose of raltitrexed in combination with radiotherapy in patients with unresectable/recurrent rectal cancer. PATIENTS AND METHODS: Patients were treated with radiotherapy (25 fractions at 2.0 Gy per fraction) five times per week for 5 weeks. Raltitrexed was administered on days 1 and 22 at 2.0, 2.6 and 3.0 mg/m(2). RESULTS: A total of 20 patients were entered into the study. Dose-limiting toxicities were recorded in three of 20 patients following the first dose of raltitrexed; one patient at 2.6 mg/m(2) (grade 3 diarrhoea, grade 3 neutropenia and grade 2 pyrexia) and two patients at 3.0 mg/m(2) (one grade 3 neutropenia and one grade 4 diarrhoea). The most common non-haematological and haematological treatment-related adverse events were diarrhoea (11 of 20, two grade 3, one grade 4) and leukopenia (eight of 20, one grade 3, one grade 4), respectively. CONCLUSIONS: The recommended dose of raltitrexed in combination with radiotherapy for future studies is 2.6 mg/m(2).

Adult↗
PubMed2002

ChlVPP/EVA hybrid versus the weekly VAPEC-B regimen for previously untreated Hodgkin's disease.

PURPOSE: To test the hypothesis that a chemotherapy regimen of relatively low toxicity and 11 weeks' duration (doxorubicin, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone [VAPEC-B]) is at least as effective in terms of disease control as 6 months' treatment with chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin (ChlVPP/EVA hybrid), which is associated with a high risk of permanent sterility. PATIENTS AND METHODS: Two hundred eighty-two patients with previously untreated Hodgkin's disease, clinical stages I/II (plus mediastinal bulk and/or B symptoms) and clinical stages III/IV were randomized at three United Kingdom and one Italian center to receive either six monthly cycles of ChlVPP/EVA hybrid or 11 weekly cycles of VAPEC-B. After chemotherapy and a restaging evaluation, radiotherapy was administered to sites of previous bulk or residual radiographic abnormality before patients were observed off treatment. RESULTS: Further accrual to the trial was halted at the planned third interim analysis in September 1996. After a median follow-up of 4.9 years, freedom from progression (FFP), event-free survival (EFS), and overall survival (OS) are all significantly better in the population treated with ChlVPP/EVA than VAPEC-B, where the comparative 5-year results are 82% and 62% (FFP), 78% and 58% (EFS), and 89% and 79% (OS), respectively. The superiority of ChlVPP/EVA was seen in both low-risk and intermediate/high-risk patients, although subset analysis suggested that ChlVPP/EVA and VAPEC-B produce equivalent results in the best-prognosis patients (Hasenclever score <or= 2, nonbulky disease). CONCLUSION: Apart from possibly in the best-prognosis group, where results are equivalent, ChlVPP/EVA hybrid produces significantly better FFP, EFS, and OS than VAPEC-B in patients with previously untreated Hodgkin's disease.

Adolescent↗
PubMed2002

Comparison of survival, palliation, and quality of life with three chemotherapy regimens in metastatic colorectal cancer: a multicentre randomised trial.

BACKGROUND: This randomised trial compared three chemotherapy regimens in the first-line treatment of advanced colorectal cancer, in terms of their effect on overall and progression-free survival; other endpoints included toxicity, symptom palliation, and quality of life. METHODS: 905 patients were randomly assigned the de Gramont regimen (n=303; folinic acid 200 mg/m(2), fluorouracil bolus 400 mg/m(2), and infusion 600 mg/m(2) on days 1 and 2, repeated every 14 days), the Lokich regimen (n=301; protracted venous infusion of fluorouracil 300 mg/m(2) daily), or raltitrexed (n=301; 3 mg/m(2) intravenously every 21 days). Analyses were by intention to treat. FINDINGS: Median follow-up of survivors was 67 weeks. For the de Gramont, Lokich, and raltitrexed groups, respectively, median survival was 294, 302, and 266 days. The hazard ratios for overall survival were 0.88 (95% CI 0.70-1.12, p=0.17) for de Gramont versus Lokich, and 0.99 (0.79-1.25, p=0.94) for de Gramont versus raltitrexed. An increase in treatment-related deaths was seen on raltitrexed (de Gramont one, Lokich two, raltitrexed 18) due to combined gastrointestinal and haematological toxicity. Patients' assessment of quality of life showed that raltitrexed was inferior to the fluorouracil-based regimens, especially in terms of palliation and functioning. INTERPRETATION: The deGramont and Lokich regimens were similar in terms of survival, quality of life, and response rates. The Lokich regimen was associated with more central line complications and hand-foot syndrome. Raltitrexed showed similar response rates and overall survival to the de Gramont regimen and was easier to administer, but resulted in greater toxicity and inferior quality of life.

Adenocarcinoma↗
PubMed2001

Integrating the oral fluoropyrimidines into the management of advanced colorectal cancer.

In colorectal cancer, leucovorin-modulated 5-fluorouracil (5-FU) has been the mainstay of both adjuvant treatment and treatment of metastatic disease for many years. In advanced disease, response rates of 10-43% are reported; efforts to improve efficacy through schedule modification, including prolonged infusions, have led to limited success. New agents with improved efficacy, tolerability and ease of administration are required. Among the newer drugs, irinotecan and oxaliplatin are becoming established as first- and second-line treatment for advanced disease. Their novel mechanisms of action have proven to be of value in 5-FU-resistant patients. In tandem with these developments, thymidylate synthase inhibition has remained an important objective and oral fluoropyrimidines such as capecitabine and UFT (uracil plus tegafur)/leucovorin have been developed with this goal in mind. Two large, phase III studies of capecitabine in metastatic disease demonstrated objective response rates of 26.6 and 24.8%. UFT/leucovorin has also been evaluated in phase III trials, with an 11.7% response rate reported. Both agents are being evaluated in combination with oxaliplatin and irinotecan, and ultimately oral fluoropyrimidines as monotherapy or combination therapy may replace intravenous (i.v.) 5-FU as first-line treatment for metastatic colorectal cancer.

Administration, Oral↗
PubMed2000

Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial.

BACKGROUND: Irinotecan is active against colorectal cancer in patients whose disease is refractory to fluorouracil. We investigated the efficacy of these two agents combined for first-line treatment of metastatic colorectal cancer. METHODS: 387 patients previously untreated with chemotherapy (other than adjuvant) for advanced colorectal cancer were randomly assigned open-label irinotecan plus fluorouracil and calcium folinate (irinotecan group, n=199) or fluorouracil and calcium folinate alone (no-irinotecan group, n=188). Infusion schedules were once weekly or every 2 weeks, and were chosen by each centre. We assessed response rates and time to progression, and also response duration, survival, and quality of life. Analyses were done on the intention-to-treat population and on evaluable patients. FINDINGS: The response rate was significantly higher in patients in the irinotecan group than in those in the no-irinotecan group (49 vs 31%, p<0.001 for evaluable patients, 35 vs 22%, p<0.005 by intention to treat). Time to progression was significantly longer in the irinotecan group than in the no-irinotecan group (median 6.7 vs 4.4 months, p<0.001), and overall survival was higher (median 17.4 vs 14.1 months, p=0.031). Some grade 3 and 4 toxic effects were significantly more frequent in the irinotecan group than in the no-irinotecan group, but effects were predictible, reversible, non-cumulative, and manageable. INTERPRETATION: Irinotecan combined with fluorouracil and calcium folinate was well-tolerated and increased response rate, time to progression, and survival, with a later deterioration in quality of life. This combination should be considered as a reference first-line treatment for metastatic colorectal cancer.

Adenocarcinoma↗
PubMed1998

Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer.

BACKGROUND: In phase II studies, irinotecan is active in metastatic colorectal cancer, but the overall benefit has not been assessed in a randomised clinical trial. METHODS: Patients with proven metastatic colorectal cancer, which had progressed within 6 months of treatment with fluorouracil, were randomly assigned either 300-350 mg/m2 irinotecan every 3 weeks with supportive care or supportive care alone, in a 2:1 ratio. FINDINGS: 189 patients were allocated irinotecan and supportive care and 90 supportive care alone. The mean age of the participants was 58.8 years; 181 (65%) were men and 98 (35%) were women. WHO performance status was 0 in 79 (42%) patients, 1 in 77 (41%) patients, and 2 in 32 (17%) patients. Tumour-related symptoms were present in 134 (71%) patients and weight loss of more than 5% was seen in 15 (8%) patients. With a median follow-up of 13 months, the overall survival was significantly better in the irinotecan group (p=0.0001), with 36.2% 1-year survival in the irinotecan group versus 13.8% in the supportive-care group. The survival benefit, adjusted for prognostic factors in a multivariate analysis, remained significant (p=0.001). Survival without performance-status deterioration (p=0.0001), without weight loss of more than 5% (p=0.018), and pain-free survival (p=0.003) were significantly better in the patients given irinotecan. In a quality-of-life analysis, all significant differences, except on diarrhoea score, were in favour of the irinotecan group. INTERPRETATION: Our study shows that despite the side-effects of treatment, patients who have metastatic colorectal cancer, and for whom fluorouracil has failed, have a longer survival, fewer tumour-related symptoms, and a better quality of life when treated with irinotecan than with supportive care alone.

Adult↗
PubMed1998

A comparative study of facial profiles in extraction and nonextraction treatment.

Evaluation of facial profiles and facial balance is a constant, continuous study and learning process for orthodontists. Tooth movement and proper positioning of the teeth to ensure favorable facial changes and to avoid unfavorable changes should be in the orthodontist's "diagnostic" mind from the very first examination. The continuous controversy concerning extraction of premolar teeth and its supposed effects on the facial profile led to the development of this study, which compares the pretreatment and posttreatment facial profiles of patients who underwent premolar extraction with those of patients who did not undergo extraction. The study comprised 170 consecutively treated patients. One hundred-eight of the patients were treated with premolar extraction, and 62 were treated without premolar extraction. The diagnostic extraction and treatment decisions were based on a total space analysis with differential extraction protocols. The Z-angle (an angular measurement) and the E-value (a linear measurement) were used to quantify and compare the pretreatment and posttreatment profiles of the two groups. Both groups completed treatment within the normal ranges of the profile measurement values with the lip profile position slightly more retrusive in the nonextraction group. The nonextraction group's posttreatment Z-angle was 5.27 degrees greater and the posttreatment E-value was 1.47 mm more negative than that of the extraction group. The extraction group began treatment with greater facial imbalance and had the greatest improvement in facial esthetics.

Adolescent↗
PubMed1998

The in vitro radiosensitivity of human head and neck cancers.

A study was made of the intrinsic radiosensitivity of 140 biopsy and surgical specimens of malignant head and neck tumours of different histologies. Using a soft-agar clonogenic assay, the material was assessed for the ability to grow in culture (colony-forming efficiency; CFE) and inherent tumour radiosensitivity (surviving fraction at 2 Gy, SF2). The success rate for obtaining growth was 74% (104/140) with a mean CFE of 0.093% (median 0.031) and a range of 0.002-1.3%. SF2 was obtained for 88 of 140 specimens, representing a success rate of 63% with a mean SF2 of 0.48 (median 0.43) and a range of 0.10-1.00. There were no significant differences in radiosensitivity between different sites of the head and neck region. There were no significant relationships between SF2 and disease stage, nodal status, tumour grade, patient age, primary tumour growth pattern and CFE. The results were compared with those for other tumour types previously analysed with the same assay. The distribution of the SF2 values for the head and neck tumours was similar to that for 145 cervix carcinomas and there was no significant difference in mean radiosensitivity between the two tumour types. Also, there was no significant difference in radiosensitivity between head and neck tumours and either breast or colorectal cancers. However, a group of eight lymphomas was significantly more radiosensitive. These results confirm the feasibility of carrying out radiosensitivity measurements using a soft-agar clonogenic assay on head and neck tumours. In addition, the work has shown that radiosensitivity is independent of many clinical parameters and that the mean value is similar to that reported for cervix carcinomas.

Head and Neck Neoplasms↗
PubMed1997

Early protrusion reduction--two phase malocclusion correction: a case report.

What is early treatment? Does early treatment imply early correction? There is confusion as to what these terms mean in clinical orthodontics today. This case report of two phase malocclusion correction addresses the issue of early treatment verses early correction. It attempts to add some perspective to the two terms and give the clinical orthodontist some sound guidelines as to whether to initiate two "phases" of treatment.

Bicuspid↗
PubMed1996

Cardiac perforation associated with continuous infusional chemotherapy.

The case history is reported of a 51-year-old man with metastatic colonic carcinoma who was receiving a continuous 5-fluorouracil infusion via a central venous catheter and who developed cardiac perforation and pericardial effusion. This complication has not previously been reported in association with continuous chemotherapy infusion.

Antineoplastic Agents↗
PubMed1996

Transforming growth factor beta 1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients.

Members of the transforming growth factor beta (TGF-beta family, in particular TGF-beta 1, are some of the most potent inhibitory growth factors in a variety of cell types. Resistance to TGF-beta 1-induced growth inhibition is frequently observed in colorectal carcinomas and is associated with tumour progression. Perturbations of TGF-beta 1 expression and function, therefore, may contribute to the loss of some constraints on tumour cell growth. In this study we have examined the expression of TGF-beta 1 and its precursor latency-associated peptide (LAP)-TGF-beta in human colorectal tumours using immunohistochemical techniques. In 86% of the tumours the LAP-TGF-beta complex was present in both the stromal and epithelial cells, whereas the mature TGF-beta 1 peptide was expressed in the glandular epithelium of 58.3% of these tumours. Intense staining for TGF-beta 1 was positively associated with advanced Dukes' stage. Furthermore, there was a significant correlation between the presence of TGF-beta 1 in the tumours and a shorter post-operative survival. This was most significant in a subgroup of patients who had received only a palliative operation. These results suggest that TGF-beta 1 expression may be useful as an independent prognostic indicator for a subgroup of patients who have a particularly poor prognosis.

Adenocarcinoma↗