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Biomedical subjects

D J Dunlop

Publications and source records attributed to D J Dunlop.

At least 19 recordsLinked to original sources
PubMed2005

An evaluation of the impact of a multidisciplinary team, in a single centre, on treatment and survival in patients with inoperable non-small-cell lung cancer.

Treatment and survival of patients with inoperable Non-small-cell lung cancer in 1997 (n=117) and 2001 (n=126), before and after the introduction of a multidisciplinary team, was examined in a single centre. There were no differences in age, sex and extent of deprivation between the two years. However, in 2001, 23% of patients received chemotherapy treatment compared with 7% in 1997 (P<0.001). Median survival in 2001 was 6.6 months compared with 3.2 months in 1997 (P<0.001).

Age Distribution↗
PubMed2004

Comparison of an inflammation-based prognostic score (GPS) with performance status (ECOG) in patients receiving platinum-based chemotherapy for inoperable non-small-cell lung cancer.

The value of an inflammation-based prognostic score (GPS) was compared with performance status (ECOG) in patients (n=109) receiving platinum-based chemotherapy for inoperable non-small-cell lung cancer. On multivariate analysis with ECOG, white cell count and the GPS entered as covariates, only the GPS was a significant independent predictor of survival (HR 1.88, 95% CI 1.25-2.84, P=0.002).

Adult↗
PubMed2003

Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer.

A score based on the combination of the systemic inflammatory response and albumin hazards ratio (HR) 1.70, 95% CI 1.23 - 2.35, P=0.001) was comparable in prognostic value to that based on stage and performance status (HR 1.48, 95% CI 1.12 - 1.95, P=0.006) in patients with inoperable non-small-cell lung cancer. The former is simple to measure and well standardised.

Adenocarcinoma↗
PubMed2003

A phase II study of carboplatin and vinorelbine in patients with poor prognosis small cell lung cancer.

AIM: The aim of this study was to evaluate the activity of the combination of carboplatin and vinorelbine in patients with poor prognosis small cell lung cancer (SCLC). Patients with good prognosis disease were included who were not medically fit to tolerate conventional chemotherapy. Activity was assessed primarily as response rate and secondarily in terms of toxicity, time to progression and survival. PATIENTS AND METHODS: Fifty-eight patients, 37 men and 21 women, with histologically or cytologically confirmed SCLC, who had bi-dimensionally measurable disease, with ECOG performance status > or = 2, with adequate haematological, hepatic and renal function received first-line chemotherapy with carboplatin (AUC x 5) day 1 and vinorelbine (30 mg/m2) days 1 and 8 of a 28-day cycle. Response was assessed after every two cycles of chemotherapy, with patients receiving a maximum of six cycles of treatment. RESULTS: The combination of carboplatin and vinorelbine is an active regimen in the treatment of SCLC, with an overall intention-to-treat response rate of 55% [95% confidence interval (CI): 42-68%] with six (10%) of patients having a complete response. Median time to progression was 18 weeks (95% CI: 15-21 weeks). Median overall survival was 26 weeks (95% CI: 21-31 weeks). Ten patients failed to complete two cycles of treatment, and were not evaluable for response for the following reasons: septic death (1 neutropaenic, 1 no myelotoxicity), non-toxic death (1 tumour eroded through the pulmonary artery, 1 ischaemic heart disease) ischaemic heart disease (1) and patient decision (5). There were a total of three toxic deaths all sepsis-complicating neutropaenia. Forty-four (76%) patients experienced grade 3 or 4 neutropaenia, six (11%) grade 3 or 4 thrombocytopaenia, 10 (13%) grade 3 lethargy, three (5%) grade 3 nausea and two (3%) grade 3 diarrhoea. CONCLUSIONS: The combination of carboplatin and vinorelbine is active against SCLC but the toxicity profile in this group of patients suggests that further evaluation is not appropriate.

Antineoplastic Combined Chemotherapy Protocols↗
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↗
PubMed2001

Non-infusional 5-fluorouracil, doxorubicin and cisplatin in the treatment of locally advanced or metastatic gastro-oesophageal adenocarcinoma.

To reduce the Hickman line-associated morbidity of continuous infusion 5-fluorouracil combined with epirubicin and cisplatin (ECF) and to investigate the need for infusional regimens, we conducted a retrospective study in patients with advanced gastro-oesophageal adenocarcinoma. Thirty-six patients, with histologically proven irresectable gastro-oesophageal adenocarcinoma were given: 60 mg/m2 cisplatin on day 1, 35 mg/m2 doxorubicin on day 1 and 500 mg/m2 5-fluorouracil on days 1 and 8 (NIACF) every 3-weeks. A median of 3 cycles was administered. The principal toxicity was myelosuppression with grade III/IV neutropenia in 47% of cycles. Neutropenic fever occurred in 5% of the cycles: non-haematological toxicity was mild and there were no treatment-related deaths. Administered dose intensity was 96.1% for doxorubicin, 93.6% for cisplatin and 90.5% for 5-fluorouracil. There were 16 partial responses and 1 complete response (overall response rate 47%, 95% confidence interval CI 31-63%); 8 patients had stable disease. Median progression-free and overall survival rates were 5 months (95% CI 4-6) and 8 months (95% CI 6-10), respectively. NIACF is a well-tolerated regimen in advanced gastro-oesophageal adenocarcinoma that precludes the need for central venous access, with activity similar to that observed with ECF.

Adenocarcinoma↗
PubMed2000

Metastatic extragonadal seminoma associated with cardiac transplantation.

A 37-year-old man who had successfully undergone cardiac transplantation for dilated cardiomyopathy presented with a history of severe pain over his left shoulder, rib cage and thoracic spine. Clinical examination revealed the presence of bony tenderness over these sites, but there was no other clinical evidence of malignancy. Further investigations suggested the presence of multiple bony metastases. Bone biopsy revealed extensive bone marrow infiltration by large undifferentiated cells showing pronounced cytoplasmic vacuolation with a striking granulomatous reaction. Immunocytochemistry revealed these anaplastic cells to be cytokeratin and placenta-like alkaline phosphatase positive but S100, CD30 and lymphoid marker negative. Analyses by in situ hybridisation of these cells revealed no evidence of Epstein-Barr virus infection. Overall the pathology suggested a diagnosis of metastatic seminoma. Confirmation of this diagnosis was obtained by the analysis of serum human chorionic gonadotrophin which was elevated at 90 IU/l. In the absence of testicular or retroperitoneal disease, it is very likely that this unusual case of metastatic seminoma was related to the patient's immunosuppressive therapy, which at diagnosis included cyclosporin and prednisolone. The patient was successfully treated with cisplatin based chemotherapy and decreased immunosuppression and remains in complete remission one year after completion of chemotherapy. Seminoma is an uncommon complication of prolonged immunosuppression with very few cases being described in the literature post-organ transplantation. This case shows that the clinical presentation of this treatable tumour in this patient population can be unusual and difficult to diagnose.

Adult↗
PubMed1999

Spontaneous regression of an anaplastic large cell lymphoma in the oral cavity: first reported case and review of the literature.

Lymphomas account for 2-5% of all oral malignancies and are the third most common in this site. This case report appears to be the first in the world literature describing spontaneous regression in the oral cavity of a subset of non-Hodgkins lymphomas known as Ki-1 anaplastic large cell lymphomas (ALCL). Ki-1 ALCL account for 2-7% of all non-Hodgkins lymphomas and the clinical presentation is variable; they may arise de novo or in the setting of a separate primary lymphoma and commonly present in the extra-nodal location. Disease severity is also variable with waxing and waning lesions at one extreme which may spontaneously regress to bone marrow involvement in around 12% of cases. This case is especially interesting since the patient is a farmer, given the recent evidence that there may be a link between non-Hodgkins lymphoma and this occupation.

Aged↗
PubMed1998

Randomized multicentre trial of filgrastim as an adjunct to combination chemotherapy for Hodgkin's disease. West of Scotland Lymphoma Group.

This study was intended to ascertain whether the adjunctive administration of filgrastim (r metHuG-CSF, Amgen) would influence the dose intensity of chemotherapy or the morbidity of myelosuppression in patients receiving MOPP or MOPP/EVAP hybrid chemotherapy for Hodgkin's disease. In a prospective randomized trial, two regimens for the treatment of Hodgkin's disease were compared. The substudy described here randomized patients receiving either regimen to receive filgrastim on the days when chemotherapy was not administered. During chemotherapy, parameters of myelosuppression were documented, including dose delays, the severity and duration of neutrophil and platelet nadirs, infective episodes, and resulting hospital admissions. In the MOPP arm, 13/25 eligible patients, and, in the MOPP/EVAP arm, 12/22 eligible patients, received filgrastim. The use of filgrastim made no statistically significant difference to the administered dose intensity for either MOPP (P = 0.57, 95% confidence interval (CI) 15-point increase to 8-point reduction) or MOPP/EVAP (P = 0.53; 95% CI 7-point increase to 11-point reduction). In patients receiving MOPP, filgrastim reduced the median duration of leucopenia (P = 0.007) and the severity of the white blood cell nadir (P = 0.036); however, no statistically significant effect (at the 5% level) was seen in platelet or haemoglobin nadirs, the number of days of in-patient hospitalization, the number of admissions for infective complications, the incidence, grade or duration of infections, or the incidence of febrile neutropenia. In patients receiving MOPP/EVAP, filgrastim had no significant effect on the duration or depth of leucopenia but was associated with a reduction in the median haemoglobin (P = 0.002) and platelet nadirs (P = 0.015). No effect on the above listed sequelae of myelosuppression was influenced by the administration of filgrastim. This study, although small, suggests that the routine use of filgrastim, aimed at influencing the administered dose intensity of conventional dose chemotherapy in Hodgkin's disease, is not warranted.

Adolescent↗
PubMed1997

CD34 positive PBPC expanded ex vivo may not provide durable engraftment following myeloablative chemoradiotherapy regimens.

We have previously demonstrated that CD34+ cells, selected from peripheral blood progenitor cells (PBPC), can be expanded in ex vivo culture and can be infused in tandem with unmanipulated PBPC with little or no toxicity. In this study, four patients (two non-Hodgkin's lymphoma (NHL), two multiple myeloma (MM)) received myeloablative conditioning prior to stem cell rescue using ex vivo expanded cells alone. The two patients with NHL received cyclophosphamide and total body irradiation (CY/TBI) and the two patients with MM, busulphan and melphalan (Bu/M). One case received an inadequate CFU-GM dose, despite expansion, and in one case the expanded cells were contaminated. No definitive conclusions may therefore be drawn concerning engraftment in these two cases. However, the other two cases received high doses of committed progenitors. Following infusion of the expanded material, all four patients failed to show sustained neutrophil engraftment and none showed evidence of platelet engraftment. Back-up, unmanipulated PBPC were therefore infused on days 14, 34, 32 and 28 and subsequently all four cases achieved satisfactory engraftment of both neutrophils and platelets. In conclusion, we feel that, CD34+ cells, expanded ex vivo using the conditions described in this report, may not provide durable engraftment following fully myeloablative conditioning.

Adult↗
PubMed1997

CD34+ cells can be selected efficiently from cryopreserved peripheral blood progenitor cells and can retain their proliferative potential.

Hematopoietic stem and progenitor cells express the CD34 antigen. Techniques have been developed that enable purified populations of CD34+ cells to be selected from hematopoietic tissues. These selected CD34+ cells have several potential applications, including CD34 selection to obtain a tumor purging effect in autologous transplantation studies and using CD34+ cells as the starting cells for ex vivo expansion studies and as a vehicle for gene transduction protocols. We have investigated the feasibility of using cryopreserved peripheral blood progenitor cells (PBPC) for CD34 selection. Cells could be recovered from cryopreservation with good yields and high viability. After CD34 selection, the final product was, on average, 84% pure, with a recovery of 54%. These cells retained extensive proliferative potential, as demonstrated by ex vivo expansion culture. We believe that cryopreserved PBPC could be thawed, and CD34+ cells could be selected and used for transplantation following high-dose chemotherapy.

Blood Cell Count↗
PubMed1996

Thoracic spinal cord compression caused by hypophosphataemic rickets: a case report and review of the world literature.

Vitamin D resistant hypophosphataemic rickets is a rare cause of spinal cord compression. The compression is caused by a combination of thickening of the laminae and calcification of the ligamentum flavum. Modern imaging techniques including CT and MRI provide excellent detail of both the level and degree of compression. MRI is particularly useful for examining the rest of the spinal cord for areas of impending compression and for postoperative follow-up. With careful surgical decompression a full neurological recovery can be achieved.

Female↗
PubMed1996

Bioavailability of subcutaneous 5-fluorouracil: a case report.

The optimal schedule for the administration of 5-fluorouracil (5-FU) in the management of advanced colorectal cancer remains to be determined. It has been suggested that this drug may be given by the subcutaneous route and that following a short infusion the bioavailability is similar to that observed after intravenous administration. We report the results we obtained in a patient treated with an intravenous bolus of 5-FU followed by a 22-h subcutaneous infusion. In this patient the bioavailability of 5-FU given by subcutaneous infusion was 0.94. The steady-state plasma levels of 5-FU reached during subcutaneous infusion were comparable with those achieved during intravenous infusion. Following four cycles of subcutaneous therapy, painless blistering was noted at the infusion sites, which healed following the cessation of subcutaneous therapy. Further studies are required to evaluate this route of therapy as an alternative to protracted intravenous therapy. The main dose-limiting side effect appears to the local skin toxicity.

Antidotes↗
PubMed1996

CD34-positive cells isolated from cryopreserved peripheral-blood progenitor cells can be expanded ex vivo and used for transplantation with little or no toxicity.

PURPOSE: The objectives of this phase I study were to assess the feasibility of using cryopreserved peripheral-blood progenitor cells (PBPC) for large-scale CD34 selection and subsequent expansion, and the safety of their use for reinfusion following chemoradiotherapy. PATIENTS AND METHODS: For 10 patients with nonmyeloid malignancy, an aliquot from a PBPC harvest was recovered from liquid nitrogen, and CD34 selected using the Isolex system (Baxter Healthcare, Newbury, United Kingdom) and expanded for 8 days ex vivo in a medium free of animal proteins but supplemented with autologous serum, stemcell factor (SCF), interleukin-1 beta (IL-1 beta), IL-3, IL-6, and erythropoietin. RESULTS: The mean increase for cell number was 21-fold, for colony-forming units-granulocyte/macrophage (CFU-GM) 139-fold, and for burst-forming units-erythroid (BFU-E) 114-fold. The expanded cells were reinfused in tandem with unmanipulated material (> or = 25 x 10(4) CFU-GM/kg). The patients did not experience any adverse effects immediately on cell infusion or within 48 hours. The 10 index patients were compared with 10 historical controls for parameters of myelosuppressive morbidity. In this small study, there were no differences in either neutrophil or platelet recovery between the patients who received expanded cells and historical controls. CONCLUSION: These data demonstrate that CD34 cells can successfully be selected from cryopreserved material, expanded ex vivo on a large scale, and safely reinfused following myeloablative conditioning regimens.

Adolescent↗
PubMed1996

Phase I/II study of gemcitabine and cisplatin in the treatment of advanced non-small cell lung cancer: preliminary results.

Sixty-six patients with advanced non-small cell lung cancer have been entered into a phase I/II study of a combination of gemcitabine and cisplatin. An initial phase I portion of the study has been completed, and 16 patients have been entered using a fixed dose of gemcitabine 1,000 mg/m2 as a 30-minute intravenous infusion weekly for 3 weeks. Cisplatin was administered on day 15 following gemcitabine with appropriate prehydration and posthydration. The study was designed to allow for sequential groups of three patients to receive three dose levels of cisplatin (60 mg/m2, 75 mg/ m2, and 100 mg/m2). Dose modification and patient numbers were to be increased at any dose level if significant toxicity was observed. The regimen was well tolerated at all doses, and the final level of cisplatin 100 mg/m2 was expanded to 10 patients before the phase II portion was opened. Neutropenia (World Health Organization grade 4 in three patients) and thrombocytopenia (grade 3 or 4 in five patients) were the main hematologic toxicities recorded. These episodes were brief and uncomplicated. Grade 3 nausea and vomiting occurred in 12 patients, but was no worse than would be expected from cisplatin alone. Alopecia, when it occurred, was minimal (no hair loss in 10 patients and grade 1 or 2 in six patients). No significant renal toxicity or neurotoxicity was seen. A phase II study with cisplatin 100 mg/m2 and gemcitabine 1,000 mg/m2 has been opened, and to date 43 patients are evaluable for response. Eighteen (42%) patients have achieved partial remissions. The study will close when 50 evaluable patients have been entered.

Adolescent↗