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Biomedical subjects

D Crowther

Publications and source records attributed to D Crowther.

At least 91 records · Page 5Linked to original sources
PubMed1991

Comparative intraperitoneal pharmacokinetics of three platinum analogues.

The pharmakokinetic profiles of intraperitoneally infused platinum analogues were determined in 13 women exhibiting minimal residual disease following surgery and systemic chemotherapy for epithelial ovarian cancer or fallopian tube carcinoma by following the disposition of tracer doses of 195mPt radiolabel. Six patients received iproplatin, four were given cisplatin and three received carboplatin. The present data demonstrate no difference in the disposition of total platinum between these three analogues, but differences in the kinetics of free platinum may exist.

Antineoplastic Agents↗
PubMed1991

Effect of verapamil on daunorubicin accumulation in lymphocytes isolated from patients undergoing chemotherapy.

Verapamil was shown to be capable of increasing intracellular daunorubicin levels in normal lymphocytes isolated from patients undergoing chemotherapy for epithelial ovarian cancer. The extent of the increase in daunorubicin accumulation was variable, occurring in the range of 0-123% as compared with intracellular daunorubicin levels attained in the absence of verapamil. No similar effect was seen in lymphocytes isolated from healthy volunteers. A tentative explanation of these data may be the induction of multidrug resistance (mdr)-like characteristics in normal lymphocytes following cytotoxic chemotherapy.

Daunorubicin↗
PubMed1991

Viridans streptococcal bacteraemia in patients with haematological and solid malignancies.

Thirty-three episodes of septicaemia caused by viridans streptococci are reported in 32 adults under treatment for malignant diseases. The underlying diseases were acute leukaemia (17), lymphoma (4), myeloma (1), small cell carcinoma of the bronchus (6), carcinoma of the breast (2) and carcinoma of the stomach (2). Important predisposing factors included severe neutropenia and oral mucositis due to intensive chemotherapeutic regimens. There was a poor response to standard empirical antibiotics and a mortality of 12%. A role for prophylactic penicillin in high risk groups is suggested.

Adolescent↗
PubMed1991

Interferon alfa-2b in addition to chlorambucil in the treatment of follicular lymphoma: preliminary results of a randomized trial in progress.

One hundred and twenty four patients with follicular lymphoma (32 with Stage III and 92 with Stage IV disease) have been randomized to receive chlorambucil alone or chlorambucil plus interferon alfa-2b. Responding patients are then randomized to receive either interferon alfa-2b maintenance therapy for up to 12 months or no further treatment. One hundred and eight patients are evaluable for response, the remainder are still receiving initial therapy. Clinical remission (complete or good partial remission) was achieved in 42/59 (71%) patients receiving chlorambucil alone and in 27/49 (55%) patients receiving the combination (P = NS). Preliminary analysis of remission duration shows a trend in favour of those patients receiving interferon throughout (P = 0.02). There is no significant difference between the groups in terms of survival, at a median follow up of 2.5 years. Interferon-associated toxicity was minor in most patients but led to discontinuation of therapy in six cases. Larger trials with longer follow-up periods are needed to confirm the beneficial role of interferon in the treatment of follicular lymphoma.

Adult↗
PubMed1991

Metallothionein levels in ovarian tumours before and after chemotherapy.

The metallothionein content of ovarian tumours is considerably higher than that found in normal ovaries (greater than 100-fold differences in mean values, P less than 0.001). There was no difference between the metallothionein content of tumours from patients who had completed chemotherapy, usually with a regimen containing a platinum drug, and tumours from untreated patients. Similarly, the level of metallothionein was not influenced by response to therapy, age, stage, histology, or tumour cell differentiation state. These data do not support the hypothesis that metallothionein content is a major determinant of tumour sensitivity in ovarian cancer.

Adult↗
PubMed1991

An analysis of prognostic factors in stage III and IV Hodgkin's disease treated at a single centre with MVPP.

Two hundred and twenty seven patients with stage IIIA-IVB Hodgkin's disease have been treated at a single centre with MVPP chemotherapy followed by radiotherapy to sites of previously bulk disease. The median follow up is 58 months. 119 patients (52%) had stage IV disease. Overall complete remission (CR) rate was 72%. Discriminant analysis of factors predictive for complete remission showed that low albumin was the only independent factor that predicted a significantly lower chance of CR. Overall five year survival was 73%. A Cox multivariate analysis demonstrated that age greater than 40 years, stage IV disease, presence of bulk disease, low serum IgG and male sex to be variables which independently predicted poorer prognosis in terms of overall survival. Stage IV and lymphocyte depleted or unclassified histologies were independently predictive for poorer progression-free survival. Patient weight greater than 70 kg and stage IV disease were adverse prognostic factors for relapse free survival. Results are compared to other published multivariate analyses of prognostic factors in advanced Hodgkin's disease.

Adult↗
PubMed1991

Treatment of relapsed Hodgkin's disease using a weekly chemotherapy of short duration: results of a pilot study in 20 patients.

Twenty patients with relapsed Hodgkin's disease have been treated with a weekly regimen of chemotherapy (VAPEC-B) comprising Adriamycin 35 mg/m2 i.v. weeks 1, 3, 5, 7, 9, 11; cyclophosphamide 350 mg/m2 i.v. weeks 1, 5, 9; etoposide 100 mg/m2 p.o. daily for 5 days, weeks 3, 7, 11; vincristine 1.4 mg/m2 i.v. weeks 2, 4, 6, 8, 10; bleomycin 10 mg/m2 i.v. weeks 2, 6, 10 and prednisolone 50 mg p.o. daily weeks 1-5, 25 mg p.o. daily weeks 6-11. All had previously received an Adriamycin containing combination and in nine cases this was for relapse following MVPP. In all but one case relapse occurred less than one year after the completion of previous treatment and in 14 cases, disease recurred within 24 weeks. Thirteen patients had extra-nodal involvement. Following six weeks of treatment 14 patients had responded (6 CR; 4 CR, uncertain; 4 PR), four had stable disease, one had progressed and one had died of sepsis. Fourteen patients proceeded to high dose cyclophosphamide and BCNU with autologous bone marrow rescue and seven of these are progression free between 4 and 156 weeks later. High dose therapy was not possible in five patients, three of whom achieved CR. Of these, two (one with bulky nodal disease and skin infiltration; one with extensive bone marrow involvement) are alive and relapse free without further treatment at 95 and 114 weeks. Overall, the regimen was well tolerated but haematological toxicity was moderate or severe in ten patients and four were admitted to hospital for treatment of suspected or confirmed septicaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Cotherapists: learning to work together.

Communication in enhancing cotherapists' therapeutic effectiveness in family/couples work is of vital importance. Drawing on interactional communication theory, the author stresses the symmetrical relationship necessary for a therapeutic cotherapy relationship. Two illustrations demonstrate the potential advantages of employing the Group Coleader's Inventory as a formal communication tool to facilitate an egalitarian relationship between therapists.

Adult↗
PubMed1990

Growth factor-assisted chemotherapy--the Manchester experience.

Stimulation of red cell production by erythropoietin and of granulocyte production by granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage-CSF (GM-CSF) has been demonstrated in several clinical studies. The first study to show that a human CSF could be used to shorten the period of neutropenia and reduce the risk of serious infection following intensive combination chemotherapy was carried out in Manchester using G-CSF. The period of neutropenia was significantly shortenened (by a median of 80%) and the neutrophil count levels were restored and above normal by 14 days after chemotherapy. In view of these results a further study was undertaken to examine the possibility of using intensive two weekly chemotherapy under cover of G-CSF. Treatment with Doxorubicin at doses of 75, 100, 125 and 150 mg/m2 was followed by infusion of G-CSF for 11 days. The neutrophil counts returned to normal within 12-14 days, allowing the delivery of up to three cycles of high dose chemotherapy at 14 day intervals. These studies demonstrated that intensive chemotherapy with dose-limiting myelodepression can be given with increased frequency under cover of G-CSF. Our studies using GM-CSF have also shown that administration by continuous i.v. infusion can reduce the period of life-threatening neutropenia following high dose Melphalan (120 mg/m2) without resort to autologous bone marrow transplantation (ABMT). In this study the period of granulocytopenia following Melphalan (less than 500 g x 10(9)/m2) was less than 15 days. This compares favourably with other series using high dose Melphalan followed by ABMT without CSF, where the duration of severe neutropenia was prolonged beyond three weeks. Although it appears that G-CSF and GM-CSF should be given either by continuous i.v. infusion or s.c. injection at doses between 3-10 micrograms/kg/day to obtain maximum biological effect, a great deal more work is required to determine optimum schedules and investigate the possibility of using more than one bioregulator.

Agranulocytosis↗
PubMed1990

Clinical studies with recombinant human granulocyte-macrophage colony-stimulating factor.

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) has been used in two clinical studies at the Christie Hospital in Manchester, United Kingdom. Short daily "bolus" injections (over 30 min) were associated with serious toxicity which included bone pain, pruritus and pericarditis. In contrast, continuous infusions did not cause any toxicity and produced significantly higher increments of the peripheral neutrophil counts. rhGM-CSF reduced the period of life-threatening neutropenia following high-dose i.v. melphalan (120 mg/m2). Also, rhGM-CSF shortened the duration of thrombocytopenia induced by this chemotherapy to less time than has been seen historically in conjunction with autologous bone marrow rescue.

Adult↗
PubMed1990

Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer.

Nine patients with progressive, metastatic disease from primary carcinoma of the colon were entered into a phase I/II study using continuous intravenous infusions of granulocyte-macrophage colony-stimulating factor (GM-CSF) and high dose melphalan (120 mg m-2). GM-CSF was given alone to six patients during the first part of the study to determine a dose that would produce a peripheral leucocyte count (WCC) greater than or equal to 50 X 10(9) 1(-1) and was initially given at 3 micrograms kg-1 day-1 and escalated to 10 micrograms kg-1 day-1 after 10 days. The infusion was discontinued when the WCC exceeded 50 X 10(9) 1(-1) and after a gap of one week, melphalan was given over 30 min. GM-CSF was recommenced 8 h later and was continued until the neutrophil count had exceeded 0.5 X 10(9) 1(-1) for greater than 1 week. One patient achieved a WCC greater than 50 X 10(9) 1(-1) with GM-CSF 3 micrograms kg-1 day-1, but the other five who entered this phase of the study required dose escalation to 10 micrograms kg-1. No toxicity attributed to GM-CSF was seen. After melphalan, the median times to severe neutropenia (less than 0.5 X 10(9) 1(-1] and thrombocytopenia (greater than 20 X 10(9) 1(-1] were 6 and 9 days respectively. The median durations of neutropenia and thrombocytopenia were 14 and 10 days respectively. All patients required intensive support with a median duration of inpatient stay of 24 days. There was one treatment related death due to renal failure. One complete and two partial remissions (33% response rate) were seen but these were of short duration (median of 10 weeks). This study demonstrates that GM-CSF given by continuous intravenous infusion produces significant increments of peripheral granulocyte counts at 3 and 10 micrograms kg-1 day-1 and is not associated with any toxicity. The duration of neutropenia and thrombocytopenia induced by high-dose melphalan appears to be reduced by the subsequent administration of GM-CSF to times which are at least as short as have been reported in historical series which have used autologous bone marrow rescue.

Adult↗
PubMed1990

The long-term effects of MVPP chemotherapy for Hodgkin's disease on bone marrow function.

Using in vitro techniques, bone marrow (BM) function has been studied in 25 patients in complete remission and at least one year after the completion of MVPP chemotherapy for Hodgkin's disease. The numbers of granulocyte/macrophage (GM-CFC) and fibroblastoid (CFU-F) progenitors were significantly lower than controls and there was no evidence of any improvement with time (median months off treatment was 30 for GM-CFC and 34 for CFU-F). In long-term BM culture production of haemopoietic cells were strikingly lower in the post-MVPP group and the development of adherent stromal cell populations was also significantly less. In addition, the yield of GM-CFC in adherent layers after four weeks of culture was significantly lower than in controls. We conclude that following MVPP chemotherapy and in apparently disease free and haematologically normal individuals there is evidence of impaired BM function up to nine years after the completion of treatment. These abnormalities may be relevant to the known increased risk of acute non-lymphocytic leukaemias in this group of patients and are likely to render the BM less able to withstand subsequent insults such as further chemotherapy or infection. The eventual development of BM failure is also a possibility and long-term follow-up of these patients is essential.

Adolescent↗
PubMed1990

The management of primary fallopian tube carcinoma.

The outcome of 30 patients with primary fallopian tube carcinoma is described. Treatment varied over the 22 year period of accrual and included combinations of surgery, radiotherapy and chemotherapy. There was an apparent increase in stage at treatment with time which was probably related to more precise staging at laparotomy and the greater use of computerized tomography. The median survival for all patients was 28 months and the 5-year survival was 18%. Ten patients received postoperative chemotherapy for residual disease with an overall response rate of 80% and median progression-free and overall survival times of 14 and 21 months respectively. The pattern of relapse was similar to that seen in ovarian carcinoma, with all but one patient having the pelvis or abdomen as the main site of recurrence. Primary fallopian tube carcinoma has a response to treatment and a tumour biology similar to that of ovarian carcinoma. It is recommended that the management of this uncommon malignancy should continue to be along the lines of ovarian carcinoma, with initial treatment by cytoreductive surgery followed by chemotherapy or radiotherapy for residual disease.

Adult↗
PubMed1990

Adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with axillary node-positive breast cancer: an update of the Guy's/Manchester trial.

Between 1976 and 1985, 391 patients (202 premenopausal, 189 postmenopausal) with operable breast cancer and positive axillary lymph nodes were randomized after total mastectomy and axillary clearance to receive cyclophosphamide, methotrexate, and fluorouracil (CMF) (n = 193) or no adjuvant therapy (n = 198). After a median follow-up of 8 years, both relapse-free survival (RFS) and survival (S) were significantly prolonged in premenopausal patients receiving CMF (RFS, P less than .001; S, P = .003). Treatment with CMF resulted in a significant improvement in RFS in premenopausal patients both with steroid receptor-positive and steroid receptor-negative tumors and also in subgroups of premenopausal patients defined by the number of axillary nodes involved. Premenopausal patients who developed permanent amenorrhea following CMF had a significantly better RFS than those who continued to menstruate. Induction of amenorrhea following CMF was related to age, with almost all patients over 40 years becoming amenorrheic. For patients less than or equal to 40 years, development of amenorrhea following CMF did not influence outcome. No difference was detected between control and CMF groups (RFS, P = .9; S, P = .9) in postmenopausal patients nor in any subgroup of these patients. The results of this trial of the efficacy of CMF for improving RFS and S have strengthened with longer follow-up.

Adult↗
PubMed1990

Five year follow-up and dose delivery analysis of cisplatin, iproplatin or carboplatin in combination with cyclophosphamide in advanced ovarian carcinoma.

Eighty eight patients with FIGO stage IIb/c (postoperative residual) or III/IV epithelial ovarian cancer were randomised to receive cycles of cyclophosphamide (600 mg/m2) with either iproplatin (240 mg/m2), cisplatin (100 mg/m2) or carboplatin (300 mg/m2). A total of six cycles were given at monthly intervals. Patients were well-balanced for major prognostic factors. There was no significant difference in overall response rate (iproplatin arm, 64.3%, cisplatin arm 72.7% and carboplatin arm 66.7%). There were more complete remissions on the carboplatin arm, 45.8% compared with 21.4% on iproplatin and 22.7% on cisplatin but the difference was not statistically significant (p = 0.11). With a median follow up of 50 months the median survival for the iproplatin arm is 18 months, for the cisplatin arm 19 months and for the carboplatin arm 24 months (p = 0.15). Toxicity was greatest with cisplatin and least with carboplatin. Myelotoxicity limited the dose delivery of iproplatin as measured by total dose, dose intensity and dose intensity product. Carboplatin is at least as effective and less toxic than cisplatin when used in conjunction with cyclophosphamide for the treatment of ovarian carcinoma, and this analogue has been selected for dose intensification studies in this tumour at the Christie Hospital.

Adult↗