Therapeutic efficacy of two different cytostatic-linked phosphonates in combination with razoxane in the transplantable osteosarcoma of the rat View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1990-07

AUTHORS

T. Klenner, F. Wingen, B. Keppler, P. Valenzuela-Paz, F. Amelung, D. Schmähl

ABSTRACT

Two new compounds, 4-[4-[bis-(2-chloroethyl)-amino-]phenyl]-1-hydroxybutane-1,1-bisphosphonic acid (BAD) and aminotris-(methylenephosphonato)diamminoplatinum(ii) (ADP) that both have cytostatic and osteotropic properties, have shown good therapeutic efficacy against an osteosarcoma which metastasizes and kills by lung metastases. We therefore combined each of these drugs with the antimetastatic agent razoxane. Razoxane (20 mg/kg i.p., 5 days/week for 6 weeks) was administered in combination with either BAD (30 mg/kg i.p.) or ADP (37·5 mg/kg i.v.) twice weekly for 3 weeks. Tumour volumes, body weight, survival time and occurrence of metastases were recorded, in addition to the measurement of the metastasis area compared to the total lung area in serial histological lung samples. In both experiments, razoxane effected a significant increase in life span while being ineffective in tumour inhibition. Razoxane in combination with BAD displayed an enhanced anticancer activity which was not significant. ADP had a good antineoplastic activity and a large increase in survival time (144 per cent I LS). Razoxane used in combination with ADP did not influence antitumour efficacy. Median survivals of both ADP-treated groups were significantly longer than the razoxane-treated group. Analysis of the lung metastasis area showed a maximum of 57 per cent for the controls while all treated groups occupied a lesser area. The lowest metastases area was found with the combination treatment BAD + RAZ (18 per cent). This was considered an antimetastatic effect, while ADP treatment effected a time delay only. No change in metastatic pattern was observed in any of the treatment groups. Histological examination showed no effect on the capillaries in the proliferating region of the tumours that could account for the lower occurrence of metastases. More... »

PAGES

345-359

References to SciGraph publications

  • 1983-12. Structure-activity relationships of various bisphosphonates in CALCIFIED TISSUE INTERNATIONAL
  • 1986-12. Mitigation of an anthracycline-induced cardiomyopathy by pretreatment with razoxane: a quantitative morphological assessment in CELL PATHOLOGY
  • 1986-06. Synthesis, antitumor activity, distribution and toxicity of 4-[4-[Bis(2-chloroethyl)amino]phenyl]-1-hydroxybutane-1 1-bisphosphonic acid (BAD), a new lost derivative with increased accumulation in rat osteosarcoma in JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
  • 1986-11. Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat in CALCIFIED TISSUE INTERNATIONAL
  • 1986-07. Treatment of Paget's disease of bone with intravenous 4-amino-1-hydroxybutylidene-1,1-bisphosphonate in CALCIFIED TISSUE INTERNATIONAL
  • 1985-01. Adjuvant treatment of colorectal cancer in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 1985-05. Inhibition by aminohydroxypropylidene bisphosphonate (AHPrBP) of 1,25(OH)2 vitamin D3-induced stimulated bone turnover in the mouse in CALCIFIED TISSUE INTERNATIONAL
  • 1983-12. Apposition and resorption of bone during oral treatment with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in CALCIFIED TISSUE INTERNATIONAL
  • 1986-02. Effects of new bisphosphonic acids on tumor-induced bone destruction in the rat in JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
  • 1987-12. 3(Amino-1,1-hydroxypropylidene) bisphosphonate (APD) for hypercalcaemia of breast cancer in BRITISH JOURNAL OF CANCER
  • 1985-11. The mutagenic activity of razoxane (ICRF 159): An anticancer agent in BRITISH JOURNAL OF CANCER
  • 1987-01. Antimetastatic effects of razoxane in a rat osteosarcoma model in CLINICAL & EXPERIMENTAL METASTASIS
  • 1987-01. Effects of antimetastatic, antiinvasive and cytotoxic agents on the growth and spread of transplantable leukemias in mice in CLINICAL & EXPERIMENTAL METASTASIS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/bf01810680

    DOI

    http://dx.doi.org/10.1007/bf01810680

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1018419391

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/2350920


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