Bleomycin, pulmonary toxicity

Simpson AB, Paul J, Graham J, Kaye SB. Fatal bleomycin pulmonary toxicity in the west of Scotland 1991-95 a review of patients with germ cell tumours. Br J Cancer 1998 78(8) 1061-6. 

Ingrassia TS, Ryu JH, Trastek VF, Rosenow EC. Oxygen-exacerbated bleomycin pulmonary toxicity. Mayo ClinProc (1991) 66,173—8. 

Interference with the formation of the bleomycin-iron complex may be the most effective way of controlling bleomycin pulmonary toxicity, a fibrosis... 

Zucker PK, Khouri NF, Rosenshein NB. Bleomycin-induced pulmonary nodules a variant of bleomycin pulmonary toxicity. Gynecol Oncol 1987 28 284-291. 

Macdonald, J. S., Schein, P. S., Hubbard, S. and DeVita, V. T. (1975) Severe bleomycin pulmonary toxicity at iow total doses in patients treated with combination chemotherapy. Clin. Res., 23, 341. 

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—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... 

Adverse effects include hyperthermia, headache, nausea and vomiting. Bleomycin has minimal myelosuppressive activity. It can display sever cutaneous and pulmonary toxicity which can be explained by the low hydrolase activity in these tissues. The pulmonary toxicity may progress to life-threatening pulmonary fibrosis. 

C. The dose-limiting toxicity of bleomycin is pulmonary toxicity and that of cisplatin is renal. Doxorubicin produces cardiotoxicity hematoxicity is dose limiting for methotrexate. 

Generic Name Bleomycin Trade Name Blenoxane Primary Antineoplastic Indication(s) Carcinoma of head, neck, cervical region, skin, penis, vulva, and testicle Hodgkin disease non-Hodgkin lymphomas Common Adverse Effects Pulmonary toxicity [interstitial pneumonitis] skin disorders [rash, discoloration] mucosal lesions fever Gl distress general weakness and malaise... 

Pulmonary toxicity is dose-limiting for bleomycin and usually presents as pneumonitis with cough, dyspnea, dry inspiratory crackles on physical examination, and infiltrates on chest x-ray. The incidence of this adverse event is increased in patients older than 70 years of age and with cumulative doses greater than 400 units. In rare cases, pulmonary toxicity can be fatal. Other toxicities are listed in Table 55-4. 

Adverse effects Pulmonary toxicity is the most serious adverse effect, progressing from rales, cough, and infiltrate to potentially fatal fibrosis. Mucocutaneous reactions and alopecia are common. Hypertrophic skin changes and hyperpigmentation of the hands are prevalent. There is a high incidence of fever and chills and a low incidence of serious anaphylactoid reactions. Bleomycin is unusual in that myelosuppression is rare. 

BLEOMYCIN ANTICANCER AND IMMUNOMODULATING DRUGS-CISPLATIN t bleomycin levels, with risk of pulmonary toxicity Elimination of bleomycin is delayed by cisplatin due to 1 glomerular filtration. This is most likely with accumulated doses of cisplatin in excess of 300 mg/m2 Monitor renal function and adjust dose of bleomycin as per creatinine clearance. Monitor clinically, radiologically and with lung function tests for pulmonaiy toxicity... 

Kharasch VS, Lipsitz S, Santis W, Hallowell JA, Goorin A. Long-term pulmonary toxicity of multiagent chemotherapy including bleomycin and cyclophosphamide in osteosarcoma survivors. Med Pediatr Oncol 1996 27(2) 85-91. 

It has been suggested that, as in the case of G-CSF, GM-CSF can increase the pulmonary toxicity of bleomycin and facilitate the development of the adult respiratory distress syndrome (ARDS), but evidence is still very sparse (SED-13,1112) (SEDA-19, 342). 

Rabinowits M, Souhami L, Gil RA, Andrade CA, Paiva HC. Increased pulmonary toxicity with bleomycin and cisplatin chemotherapy combinations. Am J Chn Oncol I990 I3(2) I32-8. 

Adamson IYR. 1976. Pulmonary toxicity of bleomycin. Exp. Health Perspect. 16 119-25... 

Answer A. It can help to know which anticancer drugs are cell-cycle specific and which have characteristic toxicities. Bleomycin fits both categories acting mainly in G2, it is cell cycle specific and is distinctive for causing mucocutaneous reactions and pulmonary dysfunction. Busulfan and procarbazine may also cause pulmonary toxicity, but neither drug is cell-cycle specific. 

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