Bleomycin toxicity

Plasma digoxin levels may decrease when the drug is administered with bleomycin. When bleomycin is used witii cisplatin, there is an increased risk of bleomycin toxicity Pulmonary toxicity may occur when bleomycin is administered with other antineoplastic drugs. Plicamycin, mitomycin, mitoxantrone, and dactino-mycin have an additive bone marrow depressant effect when administered with other antineoplastic drugs. In addition, mitomycin, mitoxantrone, and dactinomycin decrease antibody response to live virus vaccines. Dactinomycin potentiates or reactivates skin or gastrointestinal reactions of radiation therapy There is an increased risk of bleeding when plicamycin is administered witii aspirin, warfarin, heparin, and the NSAIDs. 

Bleomycin hydrolase, which inactivates bleomycin, is an enzyme that is abundant in liver and kidney but virtually absent in lungs and skin the latter two organs are the major targets of bleomycin toxicity. It is thought that bleomycin-induced dermal and pulmonary toxici-ties are related to the persistence of relatively high local concentrations of active drug. 

W.M. Bennett, et al., Fatal pulmonary bleomycin toxicity in cisplatin induced acute renal failure. Cancer Treat. Rep. 64 921-924, 1980. 

BerendN. 1985. Inhibition of bleomycin toxicity by N-acetyl cysteine in the rat. Pathology 17 108—10... 

Ward HE, Nicholson A, Berend N. 1987. Failure of systemic N-acetyl cysteine to protect the rat lung against bleomycin toxicity. Pathology 19 358-60... 

In a study of 18 patients given cisplatin and bleomycin for the treatment of disseminated testicular non-seminoma, 2 patients developed pneumonitis, and it was found that the cisplatin-induced reduction in renal function was paralleled by an increase in bleomycin-induced pulmonary toxicity. Similar results were found in a much larger study of 54 patients by the same group. A study in 2 children showed that the total plasma clearance of bleomycin was halved (from 39 to 18 mL/minute/m ) when they were also given cisplatin in cumulative doses exceeding 300 mg/m. The renal clearance in one of the children fell from 30 to 8.2 mL/minute/m although there was no evidence of severe bleomycin toxicity in either child. Two cases of fatal bleomycin toxicity have been described in patients with cisplatin-induced renal impairment. ... 

Perry DJ, Weiss RB, Taylor HG. Enhanced bleomycin toxicity during acute renal failure. Cancer TreatRep (1982) 66, 592-3. 

McCrea ES, Diaconis JN, Wade JC, et al. Bleomycin toxicity simulating metastatic nodules to the lungs. Cancer 1981 48 1096-1100. 

Cohen MB, Austin JH, Smith-Vaniz A, et al. Nodular bleomycin toxicity. Am J Clin Pathol 1989 92 101-104. 

Importantly, the toxicity of bleomycin is cumulative. Total doses in excess of 450 units are associated with a significantly increased incidence of adverse lung reactions and death. The incidence of bleomycin-induced lung toxicity has been reported between 0% and 46% with a mortality rate of 3% (5,7). As mentioned above, high cumulative dose, extreme of age, uremia, the use of supplemental oxygen, and radiation therapy are well-documented risk factors for bleomycin toxicity. Other chemotherapeutic agents (cyclophosphamide and vincristine) may also have a synergistic effect with bleomycin. Finally, bleomycin may occasionally reactivate a prior radiation-induced pneumonitis, a phenomenon known as radiation-recall. ... 

Successful therapy of bleomycin toxicity hinges on early recognition. Immediate discontinuation of the drag is mandatory. A trial of corticosteroid is a reasonable option and may prevent the progression to pulmonary fibrosis, although supported by anecdotal evidence only. Unfortunately, despite these measures, some patients experience progressive lung fibrosis. 

Newer bleomycins such as peplomycin and especially liblomycin, are more resistant to bleomycin hydrolase. This results in less lung toxicity but more bone marrow toxicity, and allows for a different spectmm of antitumor action. Bleomycin is inactive orally it is given intravenously, intramuscularly, subcutaneously, or directiy into a cavity such as the pleural cavity. The majority of dmg is excreted unchanged in the urine. 

In an attempt to reduce relapse rate and late toxicity, combined-modality therapy using lower doses of radiation and an abbreviated course of chemotherapy has been evaluated.16 The goal of decreased relapse rate has been achieved, but no overall survival benefit has been documented. A limitation of this approach is exposing patients to the additive toxicities of chemotherapy. Trials that have investigated this approach typically have incorporated between two and four cycles of a standard regimen for HL, such as ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) with involved-field radiation. At present, combined-modality therapy is considered to be a standard of care for stage I/II HL. 

Bleomycin—give test dose of 1 -2 units because of possible acute pulmonary, anaphylactoid, or severe febrile reactions must dose adjust for renal insufficiency total lifetime dose should not exceed 400 units avoid high Fi02 as it can exacerbate pulmonary toxicity... 

I 12. The answer is b. (Hardman, pp 1264-1265J Dactinomycin s major toxicities include stomatitis, alopecia, and bone marrow depression. Bleomycin s toxicities include edema of the hands, alopecia, and stomatitis. Mitomycin causes marked bone marrow depression, renal toxicity, and interstitial pneumonitis. Plicamycin causes thrombocytopenia, leukopenia, liver toxicity, and hypocalcemia. The latter may be of use in the treatment of hypercalcemia. Doxorubicin causes cardiotoxicity, as well as alopecia and bone marrow depression. The cardiotoxicity has been linked to a lipid peroxidation within cardiac cells. 

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