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Biomedical subjects

M L Slevin

Publications and source records attributed to M L Slevin.

At least 109 records · Page 6Linked to original sources
PubMed1986

A phase II study of tamoxifen in ovarian cancer.

A phase II study of tamoxifen was conducted in 22 patients with stage III and IV ovarian cancer who had failed chemotherapy and who had evaluable disease. Tamoxifen was administered at a dose of 20 mg twice daily continuously until evidence of progression. Twenty-one patients had progression of disease within 3 months and one patient had stable disease for 6 months. There were no objective responses to this treatment.

Adult↗
PubMed1986

Treatment of acute lymphoblastic leukaemia in adults.

Between 1972 and 1982, 112 consecutive previously untreated adults (aged 15-69 years, median 26) commenced therapy for acute lymphoblastic leukaemia (ALL) at St Bartholomew's Hospital. The first 63 patients entered into the study received initial treatment which comprised four cycles of adriamycin and vincristine, prednisolone and L-asparaginase with the first cycle (OPAL). In 1978, six cycles were given, with escalating doses of adriamycin and cyclophosphamide from cycle 3 (HEAV'D). Central nervous system (CNS) prophylaxis incorporated intrathecal methotrexate and cytosine arabinoside with cranial irradiation. Maintenance chemotherapy consisted of 6-mercaptopurine, cyclophosphamide and methotrexate for 3 years. Results obtained with the OPAL and HEAV'D regimens were not significantly different. The overall complete remission (CR) rate was 66% (73/111), factors correlating unfavourably with achievement of CR being advanced age (P less than 0.001) and L3 morphology/B-ALL immunophenotype (P less than 0.01). Fifty-three patients have relapsed, the bone marrow being the primary site in 43. Extramedullary relapse alone occurred in 10 (seven CNS, two testicular and one skin). Only three of the 64 patients who had complete CNS prophylaxis subsequently relapsed in the CNS as an isolated site. One patient died in CR, 19 remain in continuous CR between 2.5 and 10.5 years. The median duration of remission of the 73 patients who achieved CR was 18.5 months, factors correlating favourably with duration of CR being low blast cell count at presentation (P less than 0.002) and common ALL immunophenotype (P less than 0.04). Twenty-four patients remain alive, with a median survival of all patients of 18 months. Long-term survival is possible for approximately 20% of adults with ALL treated relatively intensively.

Acute Disease↗
PubMed1986

A prospective study of 123I-labeled monoclonal antibody imaging in ovarian cancer.

Thirty patients presenting with a pelvic mass were entered into a prospective study on the use of radioimmunoscintigraphy with the 123I-labeled monoclonal antibody HMFG2. The imaging data was obtained without knowledge of the clinical data and compared with subsequent surgical findings. A false-positive diagnosis of ovarian cancer was made in five of ten patients subsequently shown not to have ovarian cancer; thus the technique cannot be used as a screening test. A true-positive diagnosis was made in 19 out of 20 patients shown subsequently to have ovarian cancer. In 18 of these patients the distribution of uptake closely fitted the surgical findings. Methods of improving these results are described. In conclusion, radioimmunoscintigraphy is of no use in determining whether a pelvic mass is due to ovarian cancer, but has benefit in the evaluation of chemotherapy and may, in the future, prevent the need for second-look operations in some circumstances.

Antibodies, Monoclonal↗
PubMed1985

Sequential methotrexate and 5-fluorouracil in the treatment of non-small cell carcinoma of the lung.

The sequential administration of methotrexate (MTX) and 5-fluorouracil (5-FU) has been claimed to be synergistic. To investigate the potential synergism in non-small cell carcinoma of the lung (NSCCL), 16 patients were treated with a 2-hr infusion of MTX 200 mg/m2 followed after 2 hr by 5-FU 1g/m2. All patients had an Eastern Cooperative Oncology Group performance status of greater than 2 and had received no previous chemotherapy. No responses were seen. This study demonstrates that sequential MTX and 5-FU in this dosage and schedule is ineffective in NSCCL.

Adenocarcinoma↗
PubMed1985

Variable bioavailability following repeated oral doses of etoposide.

Following oral administration considerable variation in the bioavailability of etoposide has been reported between patients and with different formulations of the drug. The variation within patients following repeated doses is unknown and has therefore been studied in seven patients receiving therapy on three successive days for relapsed small cell lung carcinoma. Etoposide was administered at a dose of 400 mg orally and plasma concentrations were measured using high-performance liquid chromatography. Within-patient coefficients of variation over three successive days ranged over 19-45% for peak plasma concentrations and 16-53% for the area under the plasma concentration-time curve. There was no evidence of a trend to suggest improving or worsening absorption and accumulation did not occur. Urinary excretion was less than 25% and showed no increase over the 3 days. These data indicate that etoposide bioavailability is not constant and oral therapy may lead to unsuspected underdosing or unexpected toxicity in schedules extending over several days. Monitoring blood concentrations for a single day following oral therapy may give a misleading idea of the total bioavailability of etoposide during a course of therapy. Studies of the relationship between the pharmacokinetics of prolonged schedules of etoposide and disease outcome may lead to unreliable conclusions unless intravenous etoposide is used.

Adult↗
PubMed1985

The effect of food and concurrent chemotherapy on the bioavailability of oral etoposide.

There is no information on the effect of food or concurrent drug administration on the bioavailability of oral etoposide, despite the fact that treatment is frequently administered over several days and most often in combination with other cytotoxic agents. The influence of these factors has been studied in 11 patients, receiving combination cytotoxic therapy for extensive small cell lung carcinoma. Neither food nor concurrent oral or intravenous chemotherapy had a significant effect on the mean plasma concentrations of etoposide, achieved following oral administration. Wide variation in peak plasma concentrations and in area under the concentration time curve (AUC) occurred both between and within patients. It appears unnecessary for patients receiving etoposide (at 100 mg) to fast prior to drug administration. Furthermore, oral etoposide (at 100 mg and at 400 mg) may be given in combination with other cytotoxic agents without compromising its bioavailability.

Administration, Oral↗
PubMed1985

Cardiac arrhythmias during cytotoxic chemotherapy: role of domperidone.

Four patients receiving platinum-containing chemotherapy were treated with domperidone (20 mg) by slow intravenous injection followed by a continuous infusion for 24 h at a dose of 10 mg 24 h-1 kg-1. Cardiac monitoring and plasma potassium and domperidone concentration measurements were performed. Severe cardiac arrhythmias occurred in two patients. A control group of 14 patients treated with similar chemotherapy, without domperidone, also underwent cardiac and plasma potassium monitoring. No significant arrhythmias were seen. The electrophysiologic effects of domperidone are discussed. It is concluded that treatment with intravenous domperidone is associated with the occurrence of cardiac arrhythmias.

Antineoplastic Agents↗
PubMed1985

Cisplatin combination chemotherapy versus chlorambucil in advanced ovarian carcinoma: mature results of a randomized trial.

A randomized study to compare the efficacy of combination chemotherapy (cisplatin, doxorubicin, cyclophosphamide: PACe) with chlorambucil (CB) in International Federation of Gynecology and Obstetrics (FIGO) stage III and IV ovarian carcinoma was conducted between May 1979 and October 1983. Patients failing initial CB were subsequently eligible for treatment with PACe. Eighty-nine patients were randomized and 85 were eligible for analysis; as of date, 72 of these patients have died. The majority of patients in this study had bulky residual disease after their initial laparotomy (76%). Complete response (CR) was documented by a second laparotomy after five cycles of combination therapy or 6 to 12 months alkylating agent therapy. The overall response rate (CR plus partial response [PR]) for the combination (PACe, 68%) was significantly higher (P = .0004) than that for the chlorambucil (CB, 26%). However, the median survival was not improved (PACe, 13 months; CB, 11 months) and the survival curves were not significantly different (log rank test P = .25). The results of this study are comparable to preliminary data reported from other similar randomized studies. PACe, as administered in this study, is not indicated as routine therapy in patients with bulky residual ovarian carcinoma.

Actuarial Analysis↗
PubMed1985

Single-dose etoposide in combination with vincristine and doxorubicin in the treatment of small-cell lung cancer (SCLC).

From July 1980, 104 consecutive patients with previously untreated small-cell lung cancer (SCLC) received vincristine 1.4 mg/m2, doxorubicin (Adriamycin) 40 mg/m2, and Etoposide (VePesid) 300 mg/m2 intravenously (as a single infusion) every 3 weeks. The overall response rate (complete response plus partial response) was 58%. In 47 patients with limited disease the response rate was 66% with 21/47 (45%) complete responders. Treatment was delivered on an outpatient basis. Toxicity was mild, and in 455 rapid infusions of etoposide, there have been no adverse reactions.

Adult↗
PubMed1985

High-dose etoposide in the treatment of relapsed primary brain tumors.

Twenty-four patients with relapsed primary intracranial tumors were treated with high-dose etoposide (600-1000 mg/m2). All patients had received previous radiotherapy and 15 had had previous chemotherapy. The treatment was well-tolerated, with little toxicity. Only one patient showed a partial response, which was maintained for 78 weeks. Four patients had stable disease, for a median of 15 weeks. Etoposide failed to show useful activity in relapsed brain tumors.

Adolescent↗
PubMed1985

Allopurinol mouthwashes and 5-fluorouracil induced oral toxicity.

Allopurinol has been shown to decrease the gastro-intestinal and bone marrow toxicity of 5-fluorouracil. In an attempt to diminish mucositis resulting from 5-fluorouracil administration, whilst not affecting its systemic anti-tumour activity, an allopurinol mouthwash has been used. In six patients who experienced mucositis when treated initially with 5-fluorouracil, the use of an allopurinol mouthwash with subsequent courses resulted in a reduction of oral toxicity.

Allopurinol↗
PubMed1984

Chemotherapy of diffuse malignant mesothelioma. Phase II trials of single-agent 5-fluorouracil and adriamycin.

Twenty consecutive patients with a confirmed diagnosis of diffuse malignant mesothelioma of the pleura or peritoneum, previously untreated with chemotherapy, were studied in a Phase II trial of single-agent 5-fluorouracil. One partial response of 24 months was seen. Eleven patients were treated with single-agent Adriamycin (doxorubicin) after progression on 5-fluorouracil, and one partial response of 34 months was seen. It is concluded that 5-fluorouracil has only minimal activity in diffuse malignant mesothelioma. Preliminary data suggest that Adriamycin has little activity as a second-line agent.

Adult↗