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Biomedical subjects

M Rørth

Publications and source records attributed to M Rørth.

At least 91 records · Page 5Linked to original sources

Chemotherapy versus chemotherapy plus irradiation in limited small cell lung cancer. Results of a controlled trial with 5 years follow-up.

One hundred and forty-five patients with limited stage small cell lung cancer were included in a randomized trial to evaluate the effect of chemotherapy with or without chest irradiation. Seventy-six patients were allotted chemotherapy alone while 69 patients received the same chemotherapy plus radiotherapy, 40 Gy in split-course, administered in weeks 6 and 10 after the initiation of chemotherapy. The chemotherapy consisted of lomustine, cyclophosphamide, vincristine and methotrexate. Patients treated with chemotherapy alone survived for a median of 52 weeks compared to 44 weeks in patients receiving the combined regimen (P = 0.055). After exclusion of five early deaths and one patient refusing the irradiation plus 14 completely resected patients, the remaining 65 patients receiving chemotherapy alone and the 60 patients treated with chemotherapy plus radiotherapy were included in a new analysis. The difference in survival duration which could be ascribed to treatment with or without chest irradiation thereby diminished (P = 0.24). Eighteen months' disease-free survival was obtained in 9.2% of the 65 patients and in 9.8% of the 60 patients. The complete remission rates were 37% and 46%, respectively, (P = 0.33) and the median durations of complete remission were 40 weeks and 52 weeks (P = 0.67). Treatment failure of the primary tumour occurred in 85% of patients treated with chemotherapy alone in contrast to 61% of patients receiving the combined regimen (P = 0.005). Seventy-nine of these patients underwent autopsy at which no residual chest disease was observed in 17% and 37%, respectively (P = 0.045). The combined regimen was more toxic than chemotherapy alone resulting in significantly greater dose reductions and more pronounced thrombocytopenia. Lung and pericardial fibrosis was responsible for four deaths among the complete responders in the radiotherapy group. The combined regimen thus tended to be more efficacious with respect to tumour control at the expense, however, of increased toxicity which per se, eliminated a potential improvement of the overall therapeutical results.

Antineoplastic Combined Chemotherapy Protocols↗

Acute nonlymphocytic leukemia following treatment of testicular cancer and gastric cancer with combination chemotherapy not including alkylating agents: report of two cases.

Acute nonlymphocytic leukemia following combination chemotherapy not including alkylating agents or radiotherapy was observed in one patient treated for testicular cancer and in another treated for gastric cancer. Both patients presented clinical, cytologic, and cytogenetic findings uncharacteristic for secondary acute nonlymphocytic leukemia. It is discussed whether these two cases of leukemia indicate a risk of secondary leukemia following chemotherapy with cisplatinum and adriamycin.

Acute Disease↗

Monocyte chemotaxis in patients with nonseminomatous testicular carcinoma. Effect of chemotherapy.

The chemotactic responsiveness of blood monocytes was tested in 16 patients with nonseminomatous testicular carcinoma before, during, and after chemotherapy. All the patients initially had monocyte chemotaxis within the normal range. No correlation with the histology of the tumor, the clinical stage, or the presence in serum of alpha-fetoprotein and human chorionic gonadotropin was observed. Plasma from the patients did not inhibit the chemotaxis of normal monocytes, and serum from the patients contained no chemotactic factor inhibitor. During intensive chemotherapy with cis-platinum, bleomycin, and vinblastine a reversible defect in chemotaxis occurred without correlation to the development of fever. Two months after the completion of chemotherapy the chemotactic responsiveness was unchanged compared with pretreatment values. In conclusion, this study shows normal monocyte chemotaxis in patients with testicular carcinoma, which is in contrast to reports on a variety of other solid tumors.

Adolescent↗

Phase I study of the cisplatin analogue 1,1-diamminomethylcyclohexane sulfatoplatinum (TNO-6) (NSC 311056).

The cisplatin derivative TNO-6 was evaluated for clinical toxicity in a phase I trial. TNO-6 was given daily for 5 days every 3 weeks as a 30-min IV infusion without hydration. In all, 39 patients with advanced cancer were treated at doses of 2.5-9.0 mg/m2. No dose-limiting nephrotoxicity occurred, but evidence of mild, reversible tubular damage was found. Dose-limiting toxicity was hematologic with both thrombopenia and leukocytopenia, which with high dose levels reached WHO grade 4. Hematologic toxicity was most pronounced for pretreated patients. No antitumor activity was seen. The recommended dose for phase II trials will be 9.0 mg/m2 for previously untreated and 8.0 mg/m2 for pretreated patients.

Adult↗

Beta-2-microglobulin excretion: an indicator of long term nephrotoxicity during cis-platinum treatment?

To evaluate the value of beta-2-microglobulin as an indicator of acute and long-term cis-platinum-induced nephrotoxicity, 51Cr-EDTA clearance and serum concentration and urinary excretion of beta-2-microglobulin were measured in 18 patients treated with a regimen including cis-platinum. Before treatment all values were within the normal range. During treatment 51Cr-EDTA clearance decreased from 108 to 90 ml/min/1.73 m2 (P less than 0.02). The decrease was irreversible, while a transient 2 to 5-fold increase in beta-2-microglobulin excretion in the urine was seen during treatment. Serum beta-2-microglobulin remained unchanged. The decrease in 51Cr-EDTA clearance was not correlated to either the peak increase in the beta-2-microglobulin excretion or to the time of occurrence of the peak (R = 0.3). Thus, it is not possible to predict the long-term nephrotoxicity of cis-platinum by measuring the beta-2-microglobulin excretion during treatment.

Adolescent↗

Phagocytosis and killing of Candida albicans by blood monocytes from patients with non-seminomatous testicular carcinoma: effect of chemotherapy.

Blood monocytes were isolated from 14 patients with non-seminomatous testicular carcinoma and tested for phagocytic and fungicidal activity towards Candida albicans. Before chemotherapy, monocyte function in the patients was not different from that of normal controls. However, patients with alpha-foetoprotein in their serum had a lower phagocytic activity compared with patients without alpha-foetoprotein. No correlation with the histology of the tumor, the clinical stage or the presence in serum of human chorionic gonadotropin was observed. Serum from the patients had no influence on the functions of normal monocytes. During intensive chemotherapy with cisplatinum, bleomycin and vinblastine, a reversible impairment in phagocytosis and killing of C. albicans occurred which had no correlation with the development of febrilia. Two months after the completion of chemotherapy the monocyte functions were unchanged as compared with pretreatment values. In conclusion, the temporary depression of monocyte functions towards C. albicans during chemotherapy might, in addition to other risk factors, predispose the patient to fungal infection.

Adolescent↗

Treatment policy of surgery in small cell carcinoma of the lung: retrospective analysis of a series of 874 consecutive patients.

A therapeutic policy of surgery in the treatment of small cell carcinoma of the lung was evaluated in a retrospective series of 874 consecutive patients. All patients were included in one of six clinical trials of intensive combination chemotherapy and radiotherapy, carried out during 1973-81. General criteria of resectability, including normal appearances at mediastinoscopy, were fulfilled in 33 electively operated patients and in 46 non-operated patients. An elective operation was defined as a thoracotomy performed with the intention of pulmonary resection in a patient known to have small cell carcinoma. Pneumonectomy or lobectomy was performed in 73% of the electively operated patients. Residual macroscopic or microscopic tumour tissue was left after half of these resections. Both operated patients and non-operated patients with operable tumours survived significantly longer than 696 patients deemed to have been inoperable. There was no significant difference, however, in the duration of survival between the two subsets of operable patients. According to this analysis, a treatment policy of surgery for resectable small cell carcinoma does not lead to better overall results than treatment with chemotherapy and radiotherapy alone.

Actuarial Analysis↗

Carbon monoxide diffusing capacity: a reliable indicator of bleomycin-induced pulmonary toxicity.

Seventy-seven untreated patients with germ-cell tumors, of whom 20 had no pulmonary involvement, no clinical or radiological evidence of pulmonary disease, received 6 courses of cisplatin, vinblastine and bleomycin. Pulmonary function tests were performed before, every 3 weeks during treatment, and once a month from then on. The carbon monoxide diffusion capacity tests were normalized with respect to the actual hemoglobin concentration. During treatment a nonsignificant decrease (P greater than 0.05) was seen in the flow volume relationships, but as it was reversible it was attributed to the strenuous treatment. In contrast a significant decrease of 35% (P less than 0.01) in the corrected carbon monoxide diffusion capacity was seen in 15 of 18 evaluable patients with neither clinical nor radiological signs of pulmonary toxicity. The decrease was correlated to the increasing dose of bleomycin (r = 0.63).

Adolescent↗

Cisplatin in the treatment of advanced gastric carcinoma: a phase II study.

Twenty-one patients with advanced local or metastatic gastric carcinoma were treated with 75 mg/m2 of cisplatin every 3 weeks. Six patients had received no prior chemotherapy. One patient achieved complete tumor regression lasting 5 months, while three patients had partial responses of 2, 4, and 11 months' duration, respectively, resulting in an overall response rate of 18% (95% confidence limits: 5%-40%). All four responding patients had improvement in performance status. Two of six patients who had had no prior chemotherapy responded, while only two of 16 patients previously treated with 5-FU and doxorubicin responded.

Adult↗

Second cancer following cancer of the male genital system in Denmark, 1943-80.

The incidence of second primary cancers was investigated among 19,886 patients with prostate cancer. The analysis disclosed 594 new cancers, which was significantly less than the expected 1,176 cases (relative risk = 0.51). Deficits were observed for most sites but were only significant for cancers of the lip, lung, and gastrointestinal organs. The average age at diagnosis of prostate cancer was 72 years. It is likely that the apparent deficit in the incidence of second neoplasms resulted from less diagnostic aggressiveness in elderly patients with cancer compared with younger patients. The risk of developing a second primary cancer was also investigated in 4,290 men with testis cancer reported to the Danish Cancer Registry between 1943 and 1980. A significant 29% excess of second cancers was found (174 observed vs. 135 expected). A bimodal distribution of risk over time was found with a 67% excess seen among patients followed for 1-4 years that was mainly due to increased incidence of acute nonlymphocytic leukemia and malignant lymphomas. Among patients surviving 10 or more years, the overall excess of 32% observed was mainly due to cancers of the gastrointestinal tract and the urinary bladder. As part of the initial treatment for testis cancer, 82% of the patients received radiotherapy. Chemotherapy was rarely given before 1975 and then mostly to patients with a poor prognosis. Late effects of radiotherapy conceivably could account for some of the excess of second hematologic as well as solid neoplasms.

Denmark↗

Modification of beta 2-microglobulin in serum from patients with small cell carcinoma of the lung--correlation with the clinical course.

A beta 2-microglobulin (beta 2m) 'modifying activity' has been demonstrated by crossed radioimmunoelectrophoresis of serum. The activity could be estimated by planimetry and expressed in arbitrary units (A.U.). Elevated values of beta 2m 'modifying activity' (greater than 0.30 A.U.) has been demonstrated in 49 of 54 patients with small cell lung cancer. The values returned to normal (less than 0.30 A.U.) in eight of the ten patients achieving complete remission (CR) and in three of seven patients achieving partial remission (PR) after chemotherapy. The decrease was more pronounced (median 0.56 versus 0.16, p less than 0.01) in patients achieving CR compared with patients achieving PR. Relapse was accompanied by rising values in 11 of 15 patients monitored during chemotherapy. In nine of these patients abnormally high values of beta 2m 'modifying activity' was demonstrated more than 1 month before clinical or radiological evidence of disease progression. Total serum beta 2m was measured by radioimmunoassay. Elevated values (greater than 200 nmol/l) was found in 14 of 48 patients with small cell lung cancer. No correlation with the clinical course was found in patients monitored during chemotherapy. Estimation of total beta 2m is of no clinical value in small cell lung cancer. Estimation of beta 2m 'modifying activity, provides clinically relevant information, but is too laborious for routine clinical application. The biochemical process underlying this phenomenon should be studied further to allow development of a more simple test.

Adult↗

Non-seminomatous testicular germ cell tumours in Denmark 1976-1980. Results of treatment.

Over a 5-year period (1976-1980) 499 patients with non-seminomatous testicular germ cell tumours were included in the Danish Testicular Carcinoma Study (DATECA). The 3-year crude survival for patients in clinical stages I, II and III was 91, 77 and 45 per cent, respectively. In stage I the relapse-free survival for patients given radiation combined with bleomycin and vincristine was significantly higher than that for patients given radiation alone. No difference in the crude survival was observed. For stage II patients maintenance chemotherapy following radiation combined with bleomycin and vincristine did not improve relapse-free or crude survival. The survival of patients with non-seminomatous tumours improved significantly during the 5-year period. This improvement was probably due to the introduction of cis-platinum in the treatment.

Adult↗