Adriamycin Toxicity Research Articles

Combination chemotherapy with adriamycin and streptozotocin. II. Clincopharmacologic correlation of augmented adriamycin toxicity caused by streptozotocin.

Plasma pharmacokinetics were compared in patients with advanced sarcomas receiving adriamycin, 60 mg/m2 intravenously (iv) on day 1 every 3 wk in combination with streptozotocin, 500 mg/m2/day iv on days 1 to 5 every 3 wk, and patients receiving adriamycin alone in the same dose and schedule. The combination-treated group had greater adriamycin drug exposure (concentration X time) when serial plasma levels were analyzed by fluorescence assay and by radioimmunoassay (RIA). The plasma t 1/2 of adriamycin equivalents measured by fluorescence assay was also significantly prolonged in the combination-treated group. These changes correlated well with an increase in adriamycin-related toxicity--mucositis and myelosuppression-seen in the patients who received the combination drug therapy. Plasma streptozotocin kinetics and the incidence of streptozotocin-related side effects--hepatic and renal function abnormalities--were those published for streptozotocin alone. Evidence is presented to support the hypothesis that the increased incidence of adriamycin side effects is due to streptozotocin-related hepatic dysfunction, affecting both the detoxification and excretion of adriamycin. Combination of other drugs with adriamycin should take into account their potential for inducing hepatic dysfunction which may affect the therapeutic index of adriamycin.

The value of adriamycin in overcoming resistance to methotrexate in tissue culture

Adriamycin effectively reduces the colony-forming ability of L 1210 and L 5178Y cells in culture. Its cytotoxicity is significantly greater against cells resistant to methotrexate (MTX), whether this resistance is due to an elevated level of dihydrofolate reductase or to impaired MTX transport. In all cell lines the toxicity of adriamycin increases with dose and duration of exposure. Tritiated-adriamycin enters the cells by a process that is temperature dependent, and is reduced by the presence of various metabolic inhibitors. Drug uptake occurs against a concentration gradient. Most of the drug remains associated with the trichloracetic acid-soluble fraction (approx. 70%), and the majority of drug bound to macro-molecules is associated with the DNA. A higher drug concentration is achieved in the MTX-resistant L 5178Y cells than in the MTX-sensitive L 5178Y cells, and therefore the ability of a cell to take up adriamycin may be correlated with the drug's cytotoxicity. These findings suggest that adriamycin may be a useful agent for treating neoplasms resistant to MTX or for use in combination with MTX against mixed tumour cell populations.

Decreased cardiac toxicity of adriamycin and daunorubicin when bound to DNA.

The acute cardiotoxic effects of adriamycin and daunorubicin have been studied in isolated, perfused rat hearts. Both drugs caused a dose‐dependent decrease in rate and contractile force as well as changes in the ECG indicating a general retardation of impulse propagation. The presence of 0.47 mg/ml of herring sperm DNA in the perfusate greatly reduced the cardiotoxic effect of both drugs. The reduced toxicity is probably due to the binding of the drugs to DNA.

Adriamycin: A New Effective Therapy for Metastatic Sarcoma.

Meeting Abstracts1 May 1973Adriamycin: A New Effective Therapy for Metastatic Sarcoma.Robert S. Benjamin, M.D., Peter H. Wiernik, M.D., Nicholas R. Bachur, M.D.Robert S. Benjamin, M.D.Search for more papers by this author, Peter H. Wiernik, M.D.Search for more papers by this author, Nicholas R. Bachur, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-831_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThis study was designed to evaluate the efficacy and toxicity of adriamycin in patients with metastatic sarcomas. Thus far 27 patients have been treated; 21 are presently evaluable. The dosage schedule was based on our pharmacologic observations of a long plasma half-life in patients with normal liver function and markedly elevated plasma levels, delayed drug elimination, and severe toxicity in patients with liver disease. One dose, 60 mg/m2body surface area, was administered intravenously to patients with normal liver function. The dose was reduced by 50% to 75% for patients with liver disease, to achieve plasma levels comparable to those... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Baltimore, Maryland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1973Volume 78, Issue 5Page: 831-831KeywordsAdverse reactionsBlood plasmaBody surface areaHalf lifeLiverLiver diseasesSarcomaToxicity Issue Published: 1 May 1973 PDF DownloadLoading ...

Effect of combination treatment with adriamycin and methotrexate on the survival time of leukemic (L 1210) mice.

Because of the limiting toxicity of adriamycin (ADR, NSC-123127) on repetitive administration [9], attention was focused in this study on combination chemotherapy, employing sequential and alternating

Chronic toxicity of adriamycin: A new antineoplastic antibiotic

Adriamycin, a new antitumor antibiotic, was administered for 3 mo to rabbits and dogs by iv injection of daily single doses of 0.125, 0.250 and 0.5 mg/kg body weight. The lowest dose caused neither mortality nor any sign of toxicity with reference to body weight, blood picture and function and morphology of the liver, kidneys, heart and skin and its appendages. The testis presented some inhibition of spermatogenesis. With the higher doses the following were observed: mortality, hemorrhagic enterocolitis, arrest or reduction of body growth, alopecia and melanosis (dog), total depression of hemopoiesis with particular damage to the platelets, blood coagulation changes, hypoproteinemia, hyperazotemia, morphologic renal damage (rabbit) and depression of spermatogenesis. From the toxicologic point of view, the product behaves as a typical inhibitor of cellular reproduction. Damage to the most actively proliferating tissues was more prevalent and occurred earlier with respect to parenchymal damage.

Therapeutic effect and toxicity of adriamycin in patients with neoplastic disease.

Adriamycin is a hydroxymethyl analog of daunorubicin with antitumor effect in man. We have studied 86 patients: 44 with acute leukemia (27 children and 17 adults), and 42 solid tumors (20 children and 22 adults). Objective response was seen in 1 of 1 Wilms' tumor, 5 of 8 neuroblastomas, 2 of 3 Ewing's sarcomas, 4 of 5 reticulum cell sarcomas; 3 of 9 osteogenic sarcomas, 3 of 6 bronchogenic carcinomas, and 1 of 1 lymphosarcoma. Complete remission (M-1 marrow) was seen in 1 of 14 acute myelocytic leukemias. Of 30 acute lymphocytic leukemias, 5 had complete and 1 had partial remission. Responses lasted from 0.25 months to 10+ months with a median of 3 months. Except for patients with osteogenic sarcomas and bronchogenic carcinomas, all received prior chemotherapy. Major toxicity of adriamycin included granulocytopenia, lymphocytopenia, thrombocytopenia, anemia, marrow hypoplasia, stomatitis, vomiting, and alopecia. Activity of adriamycin in these patients with advanced disease supports its exploration in patients earlier in their therapeutic course.