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Biomedical subjects

R J Grieve

Publications and source records attributed to R J Grieve.

At least 19 recordsLinked to original sources

ChlVPP/PABlOE and radiotherapy in advanced Hodgkin's disease. The Central Lymphoma Group.

PURPOSE: The United Kingdom Central Lymphoma Group (CLG) has modified mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) by substituting mechlorethamine with chlorambucil and dacarbazine with etoposide in the treatment of patients with advanced Hodgkin's disease (HD). Prednisolone is included in the bleomycin-containing combination, and the vinca alkaloids have been switched to balance the myelotoxicity of the two component regimens. PATIENTS AND METHODS: The resulting ChlVPP/PABlOE regimen is as follows: on days 1 to 14, chlorambucil 6 mg/m2 orally, procarbazine 100 mg/m2 orally, and prednisolone 30 mg/m2 orally; on days 1 and 8, vinblastine 6 mg/m2 intravenously (i.v.); on day 29, doxorubicin 40 mg/m2 i.v.; on days 29 and 36, vincristine 1.4 mg/m2 (maximum, 2 mg) i.v., and bleomycin 10 mg/m2 i.v.; on days 30, 31, and 32, etoposide 200 mg/m2/d orally; on days 29 to 43, inclusive, prednisolone, 30 mg/m2 orally. The second full cycle restarts on day 50. Treatment continues to maximum response plus two full cycles, but with a minimum of three full cycles. Radiotherapy is administered, after chemotherapy, to sites of previously bulky disease. Since 1983, 216 patients with previously untreated, advanced Hodgkin's disease (HD) have entered this study. RESULTS: The complete remission (CR) rate after chemotherapy was 73% (95% confidence interval [CI], 67% to 79%), and after additional radiotherapy was 85% (95% CI, 80% to 90%). The failure-free survival (FFS) rate at 5 years was 68% (95% CI, 61% to 74%), and the overall actuarial survival at 5 years was 78% (95% CI, 72% to 84%). The CR rate in patients in the poorer prognostic categories was high: 81% in patients with albumin levels less than 37 g/L, 79% in patients older than 40 years of age, 84% in stages IIIB plus i.v. disease, and 79% in patients presenting with B symptoms. As expected, nausea and vomiting were not major problems, although infection, often in the context of myelosuppression, complicated almost half the cases, and 29% of patients required admission at some stage for treatment of infection. CONCLUSION: In this multicenter study, ChlVPP/PABlOE produced results comparable to those reported for MOPP/ABVD, but with less nausea and vomiting. Treatment duration was shorter than in the original MOPP/ABVD regimen, and than that used in the Cancer and Leukemia Group B (CALGB) trial. It will now be compared with PABlOE alone.

Adult

West Midlands Oncology Association trial of adjuvant chemotherapy in node-negative breast cancer.

Between 1976 and 1984, 574 patients with operable breast cancer and histologically negative axillary lymph nodes were randomly assigned after mastectomy to receive either no further treatment or chemotherapy with oral LMF (fluorouracil, 500 mg, methotrexate, 25 mg, and chlorambucil, 10 mg, on day 1; fluorouracil, 500 mg, and chlorambucil, 10 mg, on day 2). There is no overall survival or relapse-free survival benefit at a median follow-up of 10 years and 8 years, respectively. There are significantly more local relapses in the control group (P less than .01), but an excess of distant relapses in the treated group is not statistically significant (P = .24). A positive treatment effect in small tumors (relapse-free survival, odds ratio = 0.55, P = .01) and a negative effect in progesterone receptor-positive tumors (survival, odds ratios = 2.04, P = .04) is probably ascribable to chance. Analysis of various prognostic factors shows that tumor size and histological grade have a clear effect on both relapse-free interval and survival.

Antineoplastic Combined Chemotherapy Protocols

Treatment of refractory and relapsed non-Hodgkin's lymphoma with ifosfamide, methotrexate and etoposide.

The combination of ifosfamide, etoposide and methotrexate was evaluated in 22 patients with non-Hodgkin's lymphoma (NHL) whose disease had relapsed or was resistant to first-line adriamycin-containing treatment. Only 4 of the 22 patients underwent remissions, 3 of which were complete and 1, partial. Two of the complete remissions occurred in patients with "high-grade" histology who received IMVP-16 after first-line treatment had induced only a partial remission. Bone marrow suppression was the limiting toxicity of this regime, which may be of value in the salvage therapy of selected patients with NHL.

Adult

West Midlands Oncology Association trials of adjuvant chemotherapy in operable breast cancer: results after a median follow-up of 7 years. I. Patients with involved axillary lymph nodes.

The aim of this study was to test the effectiveness of a regimen of combination chemotherapy known to be active in advanced breast cancer when given as an adjuvant treatment after mastectomy. A total of 569 patients with cancer of the breast and involvement of axillary lymph nodes were randomised, after simple mastectomy with axillary sampling, to receive either no adjuvant treatment or intravenous adriamycin 50 mg, vincristine 1 mg, cyclophosphamide 250 mg, methotrexate 150 mg and fluorouracil 250 mg (AVCMF) every 21 days for eight cycles. Randomisation was stratified according to menopausal status and tumour size. Treatment was started within 14 days of surgery in 94% of patients. Eighty-eight per cent of patients received at least seven cycles of chemotherapy with no dose reduction. The median relapse-free survival was prolonged by 14 months in patients treated with AVCMF (chi2 1 = 11.7; P = 0.0006). In the premenopausal group this period was 17 months (chi2 1 = 8.8; P = 0.003) compared with 8 months in the post-menopausal group (chi2 1 = 3.3; P = 0.07). Neither overall survival nor survival in these subgroups was significantly influenced by treatment.

Adult

West Midlands Oncology Association trials of adjuvant chemotherapy in operable breast cancer: results after a median follow-up of 7 years. II. Patients without involved axillary lymph nodes.

The aim of this study was to test the effectiveness of a regimen of combination chemotherapy when given as an adjuvant treatment after mastectomy to patients with histologically negative axillary lymph nodes. A total of 574 patients with cancer of the breast and no involvement of axillary lymph nodes were randomised, after simple mastectomy with axillary sampling, to receive either no adjuvant treatment or oral fluorouracil 500 mg, methotrexate 25 mg and chlorambucil 10 mg p.o. on day 1 and fluorouracil 500 mg and chlorambucil 10 mg p.o. on day 2 (LMF) every 21 days for eight cycles. Randomisation was stratified according to menopausal status and tumour size. Treatment was started within 14 days of surgery in 97% of patients. Ninety per cent of patients received eight cycles of chemotherapy with no dose reduction. At a median follow-up of 7 years, there was no evidence that relapse-free or overall survival time were influenced by treatment.

Adult

Primary lymphoma of the penis.

Two cases of primary lymphoma of the penis are described. The penis is an extremely uncommon site for primary lymphoma and it may easily be confused with the commoner squamous cell carcinoma. It is important to make the distinction however since lymphoma will respond well to local low dose irradiation as in these cases without the need for mutilating surgery.

Humans

The value of serial bone scanning in operable breast cancer.

The value of initial and serial isotope bone scans was assessed in 685 patients with operable primary breast cancer. Nineteen (2.8 per cent) patients had a positive initial scan and negative skeletal radiographs; only nine of these developed other evidence of metastatic disease after a mean follow up of 21 months. Five hundred and ten patients had serial scans up to five years after simple mastectomy; 51 (10 per cent) had scan conversion, of whom 37 developed clinical or radiological confirmation of recurrent disease at a mean follow-up of 13 months. Compared with clinical or radiological methods for the detection of first metastases serial bone scans gave a mean lead time of five months in 15 patients and no lead time in the remaining 22 patients. Twelve of forty-five patients with radiologically proven bone metastases had negative scans. Neither initial or serial bone scanning is clinically useful or economically viable as a routine screening or follow-up procedure for patients with operable breast cancer.

Adult

Hypocalcaemia--an unusual complication of successful chemotherapy for metastatic breast cancer.

Three cases of metastatic carcinoma of the breast are described in patients who presented with hypercalcaemia. They achieved an excellent regression of their disease with combination chemotherapy but despite this they clinically deteriorated. Investigation showed them to be hypocalcaemic due to temporary hypoparathyroidism. Correction of their serum calcium resulted in good symptomatic relief. The possible mechanisms for these changes are discussed and we feel that this unusual complication of successful chemotherapy should be remembered when patients fail to improve symptomatically despite a good disease response.

Antineoplastic Agents

Pharmacokinetics of oral and intravenous fluorouracil in humans.

The pharmacokinetics of fluorouracil were examined after single 250-mg iv doses and 500-mg oral doses to female patients with breast cancer. In five patients who received intravenous fluorouracil, the mean peak plasma level of unchanged drug was 13.4 microgram/ml, the elimination half-life was 6.3 min, and the plasma clearance was 1410 ml/min. The last value is similar to the hepatic blood flow. In six patients who received oral fluorouracil, the mean peak value of unchanged drug in plasma, which occurred within 20 min of dosing, was 8.3 microgram/ml, and the fluorouracil elimination half-life was 7.2 min. The overall bioavailability of oral fluorouracil as unchanged drug was 28%, and the variation in plasma drug levels between individuals was similar following oral and intravenous doses. The data provide additional evidence of saturable hepatic metabolism of fluorouracil during the first pass.

Administration, Oral

Hospitals.

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Economics, Hospital

Exercise responses of healthy subjects in the evaluation of cardioselectivity of beta-blockers.

The effects of intravenous propranolol, metoprolol, acebutolol and placebo on exercise-induced changes in heart rate and peak flow rate (PFR) have been studied in a group of healthy subjects. The three beta-blockers produced significant and comparable reductions in exercise-induced tachycardia and the magnitude of the reduction was related to the log plasma concentration of each drug. Significant cardiac beta-blockade was detectable for three hours after giving propranolol and for four hours after metoprolol and acebutolol. The exercise-induced changes in PFR were small and variable and were not significantly affected by any of the drugs. We conclude that, contrary to published reports, exercise-induced changes in heart rate and PFR in healthy subjects do not provide a satisfactory test system for assessing the selectivity of beta-blockers.

Adrenergic beta-Antagonists

Tumour markers in breast cancer.

The clinical usefulness of 8 potential tumour markers has been evaluated in 69 patients with Stage I and II breast cancer and 57 patients with Stage III and IV. Serum CEA concentrations were raised in 13% of patients with local and 65% of those with advanced breast cancer. In patients with clinical evidence of progression or regression of tumour, serum CEA levels changed appropriately in 83% of cases. Taking 4 of the markers (carcinoembryonic antigen (CEA), lactalbumin, alpha subunit and haptoglobin) serum concentrations of one or more were raised in 33% of patients with local disease and 81% of those with advanced breast cancer. However, marker concentrations were often only marginally raised, and are unlikely to provide sensitive guide to tumour burden. CEA, lactalbumin and alpha subunit were detectable in 68%, 43% and 40% respectively of extracts of primary breast cancers.

Breast Neoplasms