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Biomedical subjects

N Niederle

Publications and source records attributed to N Niederle.

At least 127 records · Page 7Linked to original sources
PubMed1983

Efficacy of ifosfamide in refractory malignant diseases and uroprotection by mesna: results of a clinical phase II-study with 151 patients.

In a clinical phase II study 151 patients with refractory malignant diseases were treated with ifosfamide (60 mg/kg/day i.v. days 1-5, q 21-28 days). Altogether, 490 courses of treatment were given, 92 with conventional prophylactic measures (continuous infusion of 3-4 litre physiological saline plus alkalinization of the urine) and 398 with mesna prophylaxis (12 mg/kg i.v., 0, 4 and 8 h after administration of ifosfamide). The overall response rate (min. 25% tumor reduction) was 67/151 (44%) including four complete remissions in a fairly unfavourable patient group with testicular teratoma (39/87), soft tissue sarcoma (10/16), malignant melanoma (2/7), osteogenic sarcoma (3/6), Ewing's sarcoma (2/6), lymphoma and acute leukemia (5/7) or other histologies (6/22). The response rate in patients pretreated by cyclophosphamide containing regimen was 7/19 (36%) including one complete remission and one partial remission. Mesna was highly effective in reducing the frequency of hemorrhagic cystitis from 25/92 (27%) to 16/398 (4%) ifosfamide courses. The antitumor activity of ifosfamide in testicular cancer was not reduced by mesna. In conclusion, ifosfamide with the potent uroprotector mesna appears to compare favourably with the most active agents in the treatment of malignant diseases.

Cyclophosphamide↗
PubMed1983

Ifosfamide in combination chemotherapy for sarcomas and testicular carcinomas.

The efficacy of ifosfamide combination chemotherapy was studied in 164 patients, 94 with advanced testicular carcinoma and 70 with metastatic sarcoma. Ifosfamide was given at 40-60 mg/kg/day i.v. on five consecutive days every 3-4 weeks together with mesna prophylaxis with 8 mg/kg i.v. being used at 0, 4 and 8 h after ifosfamide administration. Of 70 sarcoma patients 57 were evaluable for response, of whom 49 had received prior chemotherapy. The overall response rate was 46% (26/57) including 3 complete (CR) and 14 partial remissions (PR). Ninety-four patients with germ cell tumours of the testis were treated. Of 16 seminoma patients 15 achieved CR or PR. Seventy-eight patients with nonseminomatous testicular cancer who had received previous chemotherapy were either treated with ifosfamide/etoposide (n = 63, remission rate: 30%) or ifosfamide/cisplatin (n = 15, CR + PR: 33%). These results indicate that ifosfamide alone or in combination is active in sarcomas, seminomas and teratomas and that further studies are warranted employing the drug in first-line regimens.

Adolescent↗
PubMed1983

Treatment of refractory malignant lymphomas with ifosfamide/etoposide combination chemotherapy.

Twenty patients with malignant lymphomas refractory to prior combination chemotherapy were treated with ifosfamide (40 mg/kg/day i.v. days 1-5) and etoposide (120 mg/m2/day i.v., days 1, 3, 5). Altogether, 56 courses of treatment were given with prophylaxis of urinary side effects by mesna (8 mg/kg i.v. 0, 4, 8 hours after ifosfamide). The overall response rate (min. 25% tumor reduction) was 14/20 (70%) including 5/8 partial remissions in patients with non-Hodgkin's lymphoma and 2/12 partial remissions in patients with Hodgkin's disease. The lower total response rate of 7/12 in patients with Hodgkin's disease in comparison to 7/8 in patients with non-Hodgkin's lymphoma may be related to the different sensitivity of both diseases or to differences in the extent and duration of prior chemotherapy. As combination chemotherapy with ifosfamide/etoposide proved to be effective in refractory malignant lymphomas this combination may be included in combination chemotherapy programs for the salvage therapy or the initial treatment of malignant lymphomas with the alternation of non-cross-resistant chemotherapy combinations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

[Sequentially alternating chemotherapy of non-seminomatous testicular tumors with adriamycin/cisplatin and bleomycin/vinblastine. Therapeutic success and failure with respect to histology and tumor stages].

The value of sequential alternating chemotherapy was analyzed retrospectively in 180 patients with disseminated, non-seminomatous testicular cancer. Response rates of adriamycin/cisplatin--(combination A) and bleomycin/vinblastine (combination B)--combination chemotherapy were evaluated separately with respect to tumor histology and tumor stages. Tumor response was achieved in 151 of 180 patients (84%) who were evaluable for adriamycin/cisplatin chemotherapy. Out of those, 91 of 117 patients (78%) pretreated with combination B and 60 of 63 patients (95%) without prior chemotherapy responded. Irrespective of pretreatment tumor response was observed in 131 of 157 patients (84%) evaluable for treatment with bleomycin/vinblastine. Resistance to combination A was 2.5 fold higher in embryonal carcinomas (class II of Dixon and Moore) than in choriocarcinomas (class V). Bleomycin/vinblastine-therapy failed more frequently in choriocarcinomas as compared to other histological categories (22% vs. 14%). This report also includes an analysis of treatment failures in different tumor stages. Both regimens were more frequently ineffective in tumor stages with a large tumor burden (stages II C and IV D). Patterns of cross-resistance were evaluated for both regimens. Response to adriamycin/cisplatin occurred in 18/26 patients (69%), when combination B had failed, and response to bleomycin/vinblastine was achieved in 14/24 patients (58%) when adriamycin/cisplatin had failed. In patients not responding to either regimen the treatment failure was already recognized after the first chemotherapeutic course in 93% of these cases.

Antineoplastic Agents↗
PubMed1983

Small cell lung cancer. Serial bronchofiberscopy and photographic documentation--the bridge sign.

To determine whether serial bronchofiberscopy provides better assessment of remission and relapse in chemotherapy and radiotherapy for small cell lung cancer, therapy was preceded by bronchofiberscopy with a new, high-resolution system for photographic documentation and either open-tube of bronchofiberscopic histocytologic diagnosis. Four-course cytostatic induction therapy was combined with prophylactic brain irradiation and irradiation of primary disease sites. Bronchofiberscopy was repeated after induction chemotherapy (in some cases combined with consolidating radiotherapy) and following complete remission (CR) if relapse was suspected. Sixty patients with limited-stage disease underwent a total of 152 bronchoscopies. Eight (16 percent) of those thought to be in CR by clinical, radiologic, and tumor-marker data were histocytologically tumor-positive on endoscopy. Of ten patients thought later to have had relapse following CR, four were endoscopically tumor-positive. The bridge sign is described as a further endoscopic indicator of CR. Consecutive outpatient endoscopic examinations were well tolerated, without complications. In treatment of small cell lung cancer, routine serial bronchofiberscopy is feasible and useful. It substantiates definition of CR, lowering the risk of early relapse. By better identifying the partial responder, it contributes to a rational approach for subsequent management. Finally, it enables early endoscopic detection of local recurrence in selected cases.

Antineoplastic Agents↗
PubMed1983

[The use of bronchofibroscopy in intensive care].

The bronchofibroscope has enabled the exploration of new avenues of diagnosis and treatment in intensive-care medicine. Its proper use depends on correct indication and conscientious and careful maintenance. This paper presents, first of all, the most essential technical and maintenance measures required in handling the bronchofibroscope. This is followed by a detailed description of the therapeutic use of the instrument in bronchial lavage with instillation of salbutamol, and of the more recent methods of broncho-alveolar lavage and high-frequency ventilation. Finally, indications for bronchofibroscopy in surgery and internal medicine and as an intubation aid are described.

Adult↗
PubMed1982

[Short-term induction and cyclic maintenance therapy in inoperable small cell bronchial cancer].

Since July 1978 one hundred and three consecutive patients with unresectable small cell bronchogenic carcinoma were treated with a combination of doxorubicin, cyclophosphamide and vincristine (ACO). In limited disease patients (64) the second chemotherapy course was followed by prophylactic cranial irradiation, the fourth by irradiation towards primary disease sites. Complete responders were randomised to either receive etoposide or no further maintenance therapy. Objective responses were reached in 88/100 evaluable patients, with 72% of complete remissions in limited-stage disease and 33% in extensive disease, respectively. The actuarial median survival time for limited disease patients was 15.8 months compared to 9.3 months in extensive disease (p less than 0.005). 29 of the 100 patients remain still alive, 4 for more than 24 months without disease recurrence. The survival advantage of patients reaching complete remissions relative to those who did not is highly significant (p less than 0.001). Acute gastrointestinal and hematological side effects were common, with possibly three drug-related deaths from infections during transient granulocytopenia (mean nadir: 600-900 cells/mm3). The present induction regimen using only four courses of chemotherapy produces high complete remission rates on roentgenography and bronchoscopy and improved survival in the majority of patients. Thus far any effectiveness of etoposide-maintenance therapy following ACO could not be substantiated.

Adult↗
PubMed1981

[Individualized interval shortening in the chemotherapeutic induction treatment of solid tumors (author's transl)].

Sequential chemotherapy with vinblastin and bleomycin, as well as adriamycin and cis-platin, was administered to 29 patients with disseminated malignant testicular teratoma. In order to intensify the induction phase, the intervals between drug administrations were individually shortened, with the next course of treatment following directly after the phase of critical leucocyte depression. This method was pursued over four courses of chemotherapy without dose reduction, followed by courses of chemotherapy in a conventional three-weekly rhythm. A response was obtained in 28 patients, 18 of them achieving complete remission. Taking into consideration unfavourable prognostic factors in the treatment group, this result is better than after the same chemotherapy at three-weekly intervals. Induction treatment adapted to leucocyte response carries with it the risk of higher toxicity, but this would seem to be acceptable in view of the improved long-term prognosis. This or similar intensification of the first treatment phase, for a long time used with leukaemias, could also be considered in the management of various chemotherapy-sensitive solid tumours, especially in younger patients.

Adolescent↗
PubMed1981

[Etoposide VP 16--213)--a podophyllotoxinderivative with high antitumor activity (author's transl)].

Etoposide is a semisynthetic podophyllotoxin derivative with a broad spectrum of antitumor activity and a relatively high therapeutic index. The synergism in animal with cis-platinum, cyclophosphamide, BCNU, and cytosinarabinoside is interesting for combination regimen. Mechanisms of action are inhibition of nucleoside transfer and of DNA and RNA synthesis, single stranded breaks, inhibition of protein synthesis and of microtubular assembly. While in lower concentrations etoposide is acting cell-cycle-dependent with accumulation of cells in the G2-phase it has, in high concentrations, also a cellcycle-phase-unspecific lethal effect. Most suitable is the oral and i.v. application of etoposide in fractionated doses of 80--120 mg/m2 on 3--5 consecutive days and repetition after 21 [14--28] days. Side effects are dose-limiting bone marrow toxicity, nausea, vomiting, fever, hypotension, phlebitis, mucositis, neuropathy, cardiotoxicity, alopecia. Etoposide is one of the most active single agents in small-cell bronchus carcinoma with a remission rate of 37% (10% CR), and is very active in NHL (36%), testicular carcinoma (37%), AMML (35%), choriocarcinoma (35%), and neuroblastoma (29%). The role of etoposide in combination with other active drugs in these tumors is currently investigated in bronchus and testicular carcinoma and NHL, where etoposide will belong to the drugs of the first choice in the future.

Animals↗
PubMed1981

[Chemotherapy in advanced sarcomas (author's transl)].

43 patients with metastasizing sarcomas were treated with a combination of either vincristin, adriamycin and cis-platinum (n = 21) or ifosfamide and cis-platinum at three weeks' intervals in each case. Ten patients responded to the first combination and nine to the second combination with objective tumor regression. Particularly the latter result is remarkable since 16 of the 22 patients had already been pretreated with combinations containing adriamycin. Obviously the combination of ifosfamide and cis-platinum is a promising alternative in metastasizing sarcomas of the bones and soft tissue, especially if the CYVADIC combination--which is often regarded as standard treatment--remained unsuccessful. This has no bearing on additional surgical measures or on radiotherapy which may be necessary in some patients.

Cisplatin↗
PubMed1981

[Radiotherapy in case of intracerebral formation of metastases of non-seminomatous testicle tumors (author's transl)].

The subject of this study were non-seminomatous testicle tumors with cerebral formation of metastases. Despite the relatively low radiosensitivity of the primary tumors and their regional metastases eighteen of twenty patients were free of symptoms, and a complete regression of the intracerebral tumors was shown by computed tomography and/or scintigraphy in ten of twenty cases. This regression was obtained within two or three weeks by an irradiation of the skull with a focal dose of 30 to 40 Gy. Due to the small number of patients (20), it was not possible to demonstrate a statistically different receptiveness of the cerebral metastases according to their histological subentity. Because of the subjective stress, the duration of radiotherapy should be as short as possible (e.g. 30 Gy in 10 fractions over a period of two weeks). In our opinion, irradiation is clearly indicated in case of testicle teratomas with cerebral formation of metastases. Practically the only contra-indications are a strong intracranial hypertension as well as hyperkinesia. The entire prognosis of the patient, however, is not determined by the cerebral formation of metastases but by the pulmonary metastatic extension, so that radiotherapy is an important palliative factor with regard to the survival time of these patients.

Adolescent↗