Perioperative chemotherapy in the treatment of carcinoma of the uterine cervix.

Two hundred forty-eight women from 1969-71 who underwent surgery for carcinoma of the cervix and were treated with triaziquone (0.2 mg i.v. daily) from day 2-5 after the operation, are compared to a group of 301 conventionally treated patients examined over the 3 following years. Survival rates after 5 years did not differ significantly between the 2 groups of patients, considered either globally or divided according to their clinical or surgical-pathological stage. The incidence of complications in the "treated" patients was not significantly higher, particularly considering local and general post-operative recovery. A prospective randomized study using drugs with a high cytotoxic activity in patients with tumors limited to the cervix and unfavorable prognostic factors, could in the future help evaluate the possibility of using surgical adjuvant chemotherapy in carcinoma of the cervix.

Effects of cytostatic drugs on the transmembrane potential and surface charge of cultured cells.

The transmembrane potential, the surface charge and the cell count were measured on cells cultured in vitro under the influence of various cytostatic substances. Lower concentrations of the agents induced an increase in membrane polarization. On the other hand membrane depolarization grew with both increasing exposure to cytostatic substances and rising content of the latter in the medium. The influence of higher doses was accompanied by morphological cell damage as well as a decrease in the surface charge of cells after a lengthy incubation time. Immediately after addition of chemotherapeutic substances to the cell cultures a damped oscillation of the TMP was observed. This clearly supports that the TMP is a rapidly reacting and very sensitive indicator for a great number of cell functions and an additional parameter in pretherapeutic sensitivity tests.

Trenimon: biochemical, physiological and genetic effects on cells and organisms.

The trifunctional alkylating mutagen Trenimon interferes with the genetic material of a variety of organisms and test systems with respect to the induction of point and chromosomal mutations, sister-chromatid exchanges, recombination phenomena and phage induction. Beneath these mutagenic effects several biochemical and cell physiological aspects have been investigated. In this review we discuss chemical and cell physiological effects of Trenimon, aspects of cancer therapy with Trenimon and genetic effects induced by Trenimon. The available data on mutagenic effects of Trenimon are presented according to organisms or test systems. A short discussion on a possible genetic load by therapy with Trenimon in man concludes this review. DNA damage, especially the induction of cross-linkings, seems to represent the common reason for most of the described effects of Trenimon on cells and organisms.

[Effectiveness of adjuvant chemotherapy in ovarian carcinoma]. / Zur Effektivität der adjuvanten Chemotherapie beim Ovarialkarzinom.

A report is given about the efficiency of the so called adjuvant chemotherapy in 26 cases (26 patients suffering from ovarian cancer in the stage T1M0N0) in a time of 10 years (1968-1977).--After the primary operation-therapy, a part of the patients (9) got the cytostatic drugs Trenimon or Cyclophosphamid. The patients of the control group got nothing. The survival times of both groups showed no significant distinctions. -- The results show that the adjuvant chemotherapy in cases of ovarian cancers in stage T1M0N0 can not be recommended because there are too many side effects of the these cytostatic drugs.

Detection of induced resistance in short-term-tests. Adriamycin-resistant sarcoma 180.

By treatment of the sarcoma 180 (ascites) with adriamycin over 30 passages in NMRI mice, an adriamycin-resistant tumor cell line was developed. The resistance could be detected both in animal experiments and in the short-term test. In spite of treatment of the sarcoma 180 with triaziquone over 50 passages, no resistance could be detected against triaziquone either in the in vitro test or in animal experiments. The necessary criterion for a pretherapeutic test of sensitivity or resistance--a good correlation between in vivo and in vitro results--was fulfilled in all experiments carried out.

[A casuistic contribution to therapy with gestagen in metastasizing corpus carcinoma (author's transl)]. / Kasuistischer Beitrag zur Gestagen-Therapie beim metastasierenden Korpuskarzinom.

Casuistic contribution of a sucessfully with Gestagen treated stage IV corpus carcinoma which previously had been operated and undergone radiotherapy. Ten years after the primary treatment the patient presented herself asymptomatic and clinically free of a tumor. The possible mechanism of the effect of the Gestagen-therapy is discussed as well as the indication for the administration of Gestagen in a corpus carcinoma.

[Chemotherapy of reactive exudative pleurisy in breast carcinoma]. / Khimioterapiia na reaktivniia eksudativen plevrit pri kartsinoma na mlechnata zhleza

An analysis is carried out and the results from the treatment of 84 patients with metastasized mammary gland carcinoma and reactive exudative pleurisy are reported. Monochemiotherapy is applied in 61 patients (73%), mainly with cyclphosphamide and combined (poly) chemiotherapy in 23 patients (27%). A favourable effect on the exudative pluerisy is established in 75 per cent of all the patients treated: in 77 per cent of the treated with monochemiotherapy and 70 per cent of the treated with combined (poly) chemiotherapy. Favourable effect on exudative pleurisy was observed in 80 per cent of the patients treated with cyclophosphamide and complete exudation resorption was achieved in 2/3 of them.

[Results and experiences in the immunosuppressive therapy of rheumatoid arthritis]. / Ergebnisse und Erfahrungen zur immunsuppressiven Therapie der Rheumatoiden Arthritis

An analysis of the results of treatment-in five different hospitals and with such immunosuppressants as cyclophosphamide, azathioprine, and trenimone - of 550 patients with rheumatoid arthritis showed an overall rate of improvement of 36%. Cyclophosphamide, because of the relatively small number of side effects and the excellent therapeutical results obtained, proved to be much better than the other two immunosuppressive agents. Also, because the dosage required is comparatively low, patients over procreative age could be included in the program of treatment with immunosuppressants.

[Effect of long term treatment with trenimon in chronic progressive polyarthritis]. / Uber den Langzeittherapieeffekt von Trenimon bei Polyarthritis chronica pprogressiva

It is reported on the therapeutic effects with trenimon in patients with rheumatoid arthritis half a year and one year after the end of the treatment. When critically judged the quota of success was 32.5% for the total judgement after half a year. Significant relations dosis-effect could be ascertained only for the parameters of clinical activity up to 1 year and humoral inflammatory signs after half a year. When the therapeutic success is assessed in any case the additional therapeutic expenditure must be taken into consideration. Before the beginning of the therapy there was no ascertained relation between success of therapy and duration of the disease, sex, age, activity and function.

[Immunosuppressive treatment of progressive chronic polyarthritis]. / Immunsuppressive Behandlung bei progressiv chronischer Polyarthritis

After description of forms and possibilities of the immunsuppression the results of this therapy are discussed in 47 own patients with clinically and paraclinically ascertained rheumatoid arthritis. The patients received the sum of 4.0 mg trenimon in combination with altogether 4.0 mg cyclophosphamide by means of 20 infusions with physiological saline solution as carrier substance. Under this treatment in 93.6% of the cases the findings of the examination of joints or the clinical stage improved. As to side effects incompatibilities on the side of the gastro-intestinal tract as well as leucopenias were observed. 18 patients could be after-examined after 6 years. Whilst in every case the clinical stage deteriorated, in the majority the degree of activity remained unchanged. All the results are compared with the results reported in literature. The authors are of the opinion that, when other forms of treatment have no success and contraindication are strongly taken into consideration, the progressing of the rheumatoid arthritis can be retarded by means of immunsuppressives. The pathophysiological processes can, however, scarcely be influenced causally.

[Testing of the resistance of human tumours in the short-term test (author's transl)]. / Resistenztestung von menschlichen Tumoren in Kurzzeit-Test

Various human tumours have been investigated using, as previously described an in vitro method for sensitivity testing. This test provides information both on the rates of proliferation of tumours and on their resistance to cytostatic agents.

Effect of 3-[4-amino-2-methyl-5-pyrimidinyl)ethyl[-1(2-chloroethyl)-1-nitrosourea hydrochloride on lymphoid leukemia L-1210.

A water-soluble nitrosourea, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), was tested for antitumor activity against lymphoid leukemia L-1210 in BDF1 mice. The results obtained were as follows: (1) ip--ip system: By daily administrations optimal dose for 12 days, MED (ILS40), and therapeutic ratio were found to be 18 mg/kg, 1.3 mg/kg, and 14, respectively, and by a single injection, those were found to be 46 mg/kg, 4.2 mg/kg, and 11, respectively. The therapeutic ratio of ACNU was the highest of all the drugs tested. At the neighboring dose level to optimal dose most of leukemic mice survived more than 60 days. (2) ip--iv system: Remarkable prolongation of life-span was observed by a single injection. Majority of mice administered more than 32 mg/kg of ACNU survived more than 60 days. (3) ip--po system: Remarkable prolongation of life-span was shown by a single administration and most of leukemic mice given more than 46 mg/kg of ACNU survived over 60 days. (4) iv--ip system: By a single administration of ACNU remarkable prolongation of life-span was seen and majority of leukemic mice were rescused at doses of 32 mg/kg or more. (5) iv--iv system: Result almost similar to iv--ip system was obtained. (6) iv--po system: The result in this system was similar to that in ip--po system. Thus, the compound was highly effective in leukemic mice by either its parenteral or oral administration.

[Chemotherapeutic problems in surgically treated bronchial carcinomas (author's transl)]. / Probleme der Chemotherapie beim operierten Bronchialkarzinom

There is a report about experiences of a combined surgical and chemotherapeutical therapy with 765 resected patients who had suffered from a bronchial neoplasms. 80 patients had been radically resected and treated with chemotherapy. From 235 palliatively resected persons 124 received cyclophosphamid- or trenimon-therapy after the operation. The 5 years-survival rate of the radically resected persons arose from 50,9 to 58,9% by chemotherapy. In view of the palliatively resected patients the results of 5 years-survival got worse by adjuvant chemotherapy alone or in combination with radiation. But the 3 years-survival results show better relations than the patients without adjuvant therapy. Bronchial stump fistula and empyema as well as other postoperative complications didn't arise by chemotherapy.

[Possibilities and limits of pre-therapeutic neoplasm sensitivity cytostatics tests under short-term conditions]. / Möglichkeiten und Grenzen der prätherapeutischen Sensibilitätstestung von Tumoren gegen Zytostatika im Kurzzeittest

The following cytostatic agents were tested for activity in vivo and in vitro inWalker carcinosarcoma 256 of the rat: cyclophosphamide, triaziquon, 5-fluorouracil, methotrexate, adriamycin, dactinomycin, daunorubicin, hydroxyurea, procarbazin and vincritine. With the exception of vincristine, the results of therapy in vivo could be predicted by using a rapid in vitro test system. This involved, for cyclosphosphamide, triaziquon, adriamycin, and daunorubicin, the measurement of 3H-uridine or 3H-thymidine incorporation. The activities of methotrexate and 5-fluorouracil could be determined from 3H-deoxyuridine incorporation and that of dactinomycin from 3H-uridine incorporation. The results of short-term tests (uring adriamycin, daunorubicin, and dactinomycin) in roughly 100 human tumors were compared with data in the literature on therapy with the same cytostatic agents. Good agreement was found between the results of in vitro tests and the literature data on clinical therapy.

[Correlation of in vitro testing and therapeutical results in animal transplanted tumors after cytostatic treatment]. / Korrelation von In-vitro-Testung und Therapieergebnis bei tierischen Transplantationstumoren nach Behandlung mit Zytostatika

The antineoplastic activity of 5 substances was tested in vivo and in vitro on four different tumours (plasmocytoma and melanoma Fortner III of the Syrian golden hamster, the Walker carcinosarkoma 256 and an adenocarcinoma of the rat). The substances involved were 2,3,5-triethyleniminobenzoquinone-(1,4) (triaziquone), actinomycin D, podophyllinic ethylhydrazide (mitopodozide), bleomycin and adriamycin hydrochloride. The effect of the substances in vivo was measured on the size of the tumour, and in vitro on the incorporation of 3-H-thymidine and 3-H-uridine in short-term incubations of tumour-cell suspensions. No correlation was observed between the 3-H-thymidine incorporation in vitro and the response of the tumours in vivo. On the other hand, the 3-H-uridine incorporation in the tumour-cell suspensions in vitro was in good agreement with the results of therapy in the animal experiments. This is compatible with the results of earlier experiments using other substances to investigate the possible correlation between tumour therapy and in vitro tests.