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Biomedical subjects

M Soukop

Publications and source records attributed to M Soukop.

At least 19 recordsLinked to original sources
PubMed1992

Randomised study of two doses of cisplatin with cyclophosphamide in epithelial ovarian cancer.

Cisplatin is generally accepted to be the most active cytotoxic agent for the treatment of ovarian cancer but the optimum dose remains unclear. We have performed a randomised trial to assess the importance of cisplatin dose in the treatment of advanced epithelial ovarian cancer. Patients were randomly assigned treatment with 50 mg/m2 (low dose) or 100 mg/m2 (high dose) cisplatin plus 750 mg/m2 cyclophosphamide, for a maximum of six cycles with intervals of 3 weeks. We planned to recruit 300 patients, but an interim analysis on the first 165 indicated a highly significant survival difference (p = 0.0008). Recruitment was therefore stopped and the trial patients were followed-up for 12 months longer. The relative progression rate (high-dose/low-dose) after 12 months' extra follow-up was 0.55 (95% confidence interval 0.37-0.81, p = 0.003) and the relative death rate 0.53 (0.34-0.81, p = 0.003). Overall median survival was 69 weeks in the low-dose group and 114 weeks in the high-dose group. Residual disease extent before chemotherapy had an important influence--patients with lesions of less than 2 cm did best; if given high-dose cisplatin their median survival was 3 years. 56 low-dose and 45 high-dose patients completed six cycles of chemotherapy; 15 and 9 patients, respectively, were withdrawn early because of progressive disease and treatment was stopped in 6 and 25, respectively, because of unacceptable side-effects or patient refusal. Toxic effects were significantly greater in the high-dose group, especially those on the nervous system and ears, alopecia, vomiting, and anaemia. Although the higher dose of cisplatin clearly leads to better results in terms of survival, its overall clinical benefit in the management of ovarian cancer will depend on further improvements in measures to alleviate toxic effects.

Adult↗
PubMed1992

Extrapulmonary small cell carcinoma of bone.

Small cell carcinoma has been reported to arise in many extrathoracic sites. However, such tumours arising from bone have not been previously described. We report what we believe is the first reported case of extrapulmonary small cell carcinoma of bone. The tumour arose from the fifth dorsal vertebra in a 60 year old woman. The patient was treated with local radiotherapy and combination chemotherapy and remains in remission, 18 months after diagnosis. As such extrathoracic small cell tumours are rare, there seem to be no clear-cut guidelines for treating them, but combination chemotherapy is recommended.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Ondansetron compared with metoclopramide in the control of emesis and quality of life during repeated chemotherapy for breast cancer.

This was a multicentre, randomised, double-blind, parallel-group study which included female breast cancer patients, receiving their first of 6 scheduled courses of chemotherapy (cyclophosphamide greater than or equal to 500 mg/m2). Patients received an intravenous dose of 16 mg dexamethasone with either 8 mg ondansetron or 60 mg metoclopramide before chemotherapy, followed by oral dosing with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days. A total of 93 patients were treated with ondansetron and 94 patients with metoclopramide. On day 1 of their first course of treatment 91 and 60% of patients in the ondansetron and metoclopramide groups respectively were free of emesis (p less than 0.001). Over the 5-day treatment period, the corresponding figures were 81 and 48% (p less than 0.001). The results for nausea also revealed highly statistically significant treatment differences (p less than 0.001) in favour of ondansetron for both day 1 and day 1-5 analyses of the first treatment course. Over the series of courses, 67% of patients receiving ondansetron completed all 6 courses with a maximum of 2 emetic episodes on their worst day, compared with 28% of patients receiving metoclopramide (p less than 0.001). A similar analysis for nausea revealed that 49% of patients receiving ondansetron completed all 6 courses with 'none' or 'mild' nausea compared with 27% of patients receiving metoclopramide (p less than 0.001). These differences were reflected in quality of life data (Rotterdam Symptom Checklist). After the first course of treatment, a statistically significant improvement (p = 0.002) in the psychological subscale scores was observed after ondansetron compared with metoclopramide. No differences were observed in the physical or functional activity subscales after the first course. However, the quality of life results over the series of courses revealed a more pronounced difference in favour of ondansetron in the psychological subscale scores (p less than 0.001) as well as trends in favour of ondansetron in the physical (p = 0.096) and functional activity (p = 0.056) subscales. Extrapyramidal symptoms were reported in 19% of patients in the metoclopramide group and resulted in 15% of patients withdrawing from their randomised anti-emetic schedule, either during or between treatment courses. Other adverse events were generally minor in nature and did not necessitate withdrawal from treatment. In conclusion, this study shows that ondansetron is significantly superior to metoclopramide (each with a single pre-treatment dose of dexamethasone) in the control of emesis over 6 courses of chemotherapy for breast cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Successful use of cisplatin to treat metastatic seminoma during cisplatin-induced acute renal failure.

A chemotherapeutic regimen including cisplatin was administered to a man with extragonadal seminoma and cisplatin-induced acute renal failure. Three doses of cisplatin (30, 50, and 100 mg/m2) were given in conjunction with hemodialysis. Pharmacokinetic data for free and total plasma platinum were obtained. The patient also received one dose of carboplatin and a course of radiation therapy. Complete remission was achieved, and useful renal function returned. Cisplatin can be used successfully during acute renal failure.

Acute Kidney Injury↗
PubMed1991

Comparison of dexamethasone and ondansetron in the prophylaxis of emesis induced by moderately emetogenic chemotherapy.

A multicentre, randomised, double-blind, cross-over trial was done to compare the efficacy and safety of a serotonin receptor antagonist--ondansetron--and dexamethasone in the prophylaxis of acute and delayed emesis and nausea induced by moderately emetogenic non-platinum-containing chemotherapy regimens. Patients were treated as outpatients and received intravenous ondansetron 4 mg or dexamethasone 8 mg before chemotherapy and oral maintenance (ondansetron 4 mg every 6 h and dexamethasone reducing from 4 mg to 1 mg 6-hourly between days 1 and 5) for 5 days. 112 patients were treated (38 men, 73 women, 1 with no gender recorded; age range 30-73 years) and 100 were evaluable for cross-over analysis. Patients taking ondansetron or dexamethasone reported no significant difference in complete and major control of acute (83% vs 79%, p = 0.46) or delayed (82% vs 88%, p = 0.214) emesis (vomiting plus retches). Significantly more patients on dexamethasone (87%) than on ondansetron (72%) reported control of delayed nausea (days 2-5) (p = 0.003). Both drugs were well tolerated with no significant difference in the number of adverse events, and this is reflected by similar patient preference for ondansetron (40%) and dexamethasone (30%) (p = 0.244). Both drugs offer adequate out-patient control of chemotherapy-induced emesis; however, dexamethasone has an advantage in the control of delayed nausea, and also in terms of cost and resource allocation.

Acute Disease↗
PubMed1991

Phase I study of the anthrapyrazole biantrazole: clinical results and pharmacology.

In a phase I study the anthrapyrazole biantrazole (Warner-Lambert Company) was given to 41 patients with tumour refractory to existing therapy. The drug was given i.v. weekly for 3 weeks, with a 3-week interval between courses. At the 1st week a full pharmacokinetic study was performed, and at weeks 2 and 3, blood samples were taken at 1 and 6 h following treatment to check for drug accumulation. Biantrazole pharmacokinetics were linear with respect to the AUC (r = 0.924) over the full range of doses studied (4-36 mg/m2) but exhibited large inter-patient variations at each dose level. Elimination was triphasic, comprising two rapid early phases and a long terminal half-life (mean, 14.1 +/- 7.8 h). There was no evidence of drug accumulation over the 3-week treatment period. Approximately 12% of the parent drug was excreted unchanged in the urine together with two non-circulating, more water-soluble metabolites. Biantrazole was well tolerated but did cause moderate emesis at doses of greater than 18 mg/m2 and mild alopecia. The dose-limiting side effect was leucopenia, with no other major toxicity being observed. One patient developed biventricular failure that was not clearly related to biantrazole administration. On the present schedule, the recommended dose of biantrazole is 24 mg/m2. No response were seen in this patient population.

Adolescent↗
PubMed1991

Mechlorethamine, vinblastine, procarbazine and prednisolone (MVPP) for advanced Hodgkin's disease.

Between January 1972 and October 1985, 60 patients with advanced Hodgkin's disease were treated with mechlorethamine/vinblastine/procarbazine/prednisolone (MVPP). The complete remission (CR) rate was 50%; the introduction of computed tomography in 1980 reduced the proportion of CR from 62% to 30% (P = 0.017) as a consequence of residual mediastinal abnormality of uncertain significance. With a median follow-up of 9 years, actuarial 5 and 10-year overall survival was 70% and 57%, respectively, with 79% and 65% free from Hodgkin's disease. Only age and pathological subtype influenced survival sufficiently to be of prognostic significance, though the effect of serum albumin, ECOG performance status and B symptoms on Hodgkin's disease mortality may have been clinically important.

Adolescent↗
PubMed1991

Randomised controlled study of relaxation training.

In a study lasting 12 weeks, relaxation training was evaluated as a coping resource for cancer patients. 80 patients of both sexes were randomised to relaxation training and to a control (no training) group (40 in each). Scores for anxiety, depression and psychiatric morbidity were obtained at 0, 6 and 12 weeks with well-known questionnaires and a new anxiety and depression scale, the effects of serious illness (ESI) scale. 71 patients (32 men and 39 women) successfully completed the study. Results showed that relaxation training and control group scores were similar at 0 weeks. Higher anxiety, depression and psychiatric morbidity scores were reported by all patients at 6 and, to a lesser extent, at 12 weeks with greater differences in women. Female controls invariably reported significantly higher scores at 6 and 12 weeks on all indices. Male controls reported significantly higher anxiety scores only at 6 and 12 weeks.

Adolescent↗
PubMed1991

Alfacalcidol is a nontoxic, effective treatment of follicular small-cleaved cell lymphoma.

Thirty-four patients with progressive low grade non-Hodgkin's lymphoma were treated with 1 microgram oral alfacalcidol daily. Complete response was seen in four patients and a partial response in four patients with an overall response rate of 24%. Median duration of response was 14 months. Disease stabilised in ten other patients (29%) and 16 patients (47%) had tumour progression. In the sub-group of patients with follicular, small-cleaved cell-lymphoma the overall response to treatment was 29%. Apart from one patient who had a mild transitory elevation of serum calcium there was no recorded toxicity from alfacidol. These results indicate that alfacalcidol has significant antitumour activity in patients with low grade non-Hodgkin's lymphoma of the follicular, small-cleaved cell type.

Calcitriol↗
PubMed1991

Molecular monitoring of low grade non-Hodgkin's lymphoma by gene amplification.

Molecular monitoring by the polymerase chain reaction was used to detect and follow minimal disease in working formulation category B and C on non-Hodgkin's lymphoma. Rearrangement of the bcl-2 gene served as the target for gene amplification. Thirty patients were studied. Bone marrow histology was compared to PCR analysis of bone marrow aspirate and blood. PCR upstaged disease status in approximately 50% of patients. Results are shown from a patient whose disease was followed with PCR during chemotherapy from initial remission to relapse. We conclude that PCR of bone marrow and blood can be used to upstage disease status in low grade lymphoma and PCR of blood may be used to monitor response to treatment with obvious patient benefit. The general approach of molecular monitoring provides a means for appraising therapies in the setting of subclinical disease.

Base Sequence↗
PubMed1991

Long term results of cyclophosphamide, adriamycin and platinum chemotherapy in advanced epithelial ovarian cancer.

Between January 1980 and December 1983, 57 consecutive patients with advanced epithelial ovarian cancer (FIGO Stage IIc n = 5; III n = 45; IV n = 7) were treated with 6 cycles of cyclophosphamide 600 mg/m2, adriamycin 30-45 mg/m2 and platinum 50 mg/m2 (CAP) at 3 weekly intervals. Pathological complete remission (CR) was documented in 10 (18%) and 4 with no residual disease after primary cytoreductive surgery were free from progression (FFP). There were 19 partial remissions (PR) giving a 51% overall response rate. The median duration of CR was 33 months from second look surgery. Median survival (MS) for all patients was 22 months. Multivariate analysis indicated that response to chemotherapy was the most important prognostic factor, with MS for CR of 53 months, PR 23 months and stable or progressive disease 11 months (p = 0.001). Most CR (8 of 10) occurred in patients with minimal residual disease (no single lesion greater than 2.0 cm), but extent of disease, though significant in univariate analysis of prognostic factors was not an independent predictor of survival. Six patients (11%) are alive and tumour free with a minimum follow-up of 7 years. All had FIGO Stage III disease at presentation and four had no residual tumour after primary surgery.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Epirubicin at two dose levels with prednisolone as treatment for advanced breast cancer: the results of a randomized trial.

Two hundred eleven patients with advanced breast cancer were randomized to receive either epirubicin (E) 50 mg/m2 and prednisolone (LEP) or E 100 mg/m2 and prednisolone (HEP). The intended treatment consisted of 16 courses of LEP or eight courses of HEP given at 3-weekly intervals. Reasons for stopping treatment early included progressive disease, stable disease without symptomatic improvement, or severe toxicity deemed intolerable by either the patient or physician. Toxicity was recorded at 3-weekly and response at 9-weekly intervals using the World Health Organization (WHO) criteria of response and toxicity. Two hundred nine patients were eligible for analysis, 98% of whom have been followed for more than a year. One hundred four patients received LEP and 105 HEP. Significantly worse myelosuppression, alopecia, nausea and vomiting, and mucositis were seen in the high-dose arm (P less than or equal to .001). More patients in the LEP arm stopped treatment before the fourth course than in the HEP arm, and the commonest reason for stopping was progressive disease. A similar median number of courses was given in each arm. There was a significantly higher response in the HEP arm (HEP - complete response [CR] + partial response [PR] = 41%, LEP - CR + PR = 23%). Despite this, no statistically significant differences was seen in overall survival or progression-free interval. The median survival for HEP and LEP was 44 and 46 weeks, respectively.

Adult↗
PubMed1990

Hypothesis: symmetrical cutaneous lymphoma.

Patients with malignant lymphoma may have cutaneous and subcutaneous involvement that exhibits a striking symmetry about the coronal axis. The symmetry of these lesions may be caused by site-specific migration from the circulation, preferential proliferation by lymphocytes of the neoplastic clones at defined anatomical sites, or both mechanisms. Similar behaviour by benign lymphocytes may explain the symmetry and selective anatomical distribution of lesions in other skin diseases.

Adult↗
PubMed1990

Longstanding pleural effusion in an elderly man due to non-Hodgkin's lymphoma (multilobulated nuclear cell type).

A 68-year-old man presented with left sided pleural effusion. Investigations were suggestive of non-Hodgkin's lymphoma of multilobulated nuclear cell type. Symptomatic treatment by repeated thoracic aspiration was carried out every three to four months over nine years, after which the patient developed left axillary lymphadenopathy and a chest wall mass. Biopsy of the mass revealed multilobulated B cell lymphoma. Complete remission including disappearance of the pleural fluid was achieved with combination chemotherapy. Pleural effusion was the only clinical feature of lymphoma for nine years and this has not been described before.

Aged↗