Pneumonitis bleomycin

A potentially fatal lung toxicity occurs in 10 to 20% of patients receiving bleomycin. Patients particularly at risk are those who are over 70 years of age and have had radiation therapy to the chest. Rarely, bleomycin also may cause allergic pneumonitis. Bleomycin skin toxicity is manifested by hyperpigmentation, erythematosus rashes, and thickening of the skin over the dorsum of the hands and at dermal pressure points, such as the elbows. Many patients develop a low-grade transient fever within 24 hours of receiving bleomycin. Less common adverse effects include mucositis, alopecia, headache, nausea, and arteritis of the distal extremities. 

Chemotherapy drugs can directly or indirectly cause acute pneumonitis (bleomycin, carmustine, gemcita-bine, methotrexate, mitomycin, procarbazine, and vinca alkaloids) pulmonary fibrosis (bleomycin, carmustine, cyclophosphamide, methotrexate, and mitomycin) hypersensitivity pneumonitis (bleomycin, methotrexate, and procarbazine) noncardiogeneic pulmonary edema (cytarabine, cyclophosphamide, methotrexate, mitomycin, and teniposide). Docet-axel is associated with fluid retention, which may result in pulmonary edema or pleural effusion. Some of these conditions respond to corticosteroid therapy but some cases of pulmonary fibrosis are fatal. 

Bleomycin -antitumor antibiotic that causes DNA strand breakage -dose-related pneumonitis -mucocutaneous effects (stomatitis, mucositis) -acute pulmonary edema -fever in 50% -hyperpigmentation (can rarely be DLT)... 

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. 

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. 

Bleomycin Nausea and vomiting fever anaphylaxis and other allergic reactions phlebitis ai in ecuon site Pneumonitis and pulmonary fibrosis rash and hyperpigmenwtion stomatitis alopecia Raynaud s phenomenon cavitating granulomas haemorrhagic cystitis... 

Bleomycin is also associated with a hypersensitivity pneumonitis. This should be considered when interpreting cytological swabs in patients treated with the drug, since the acute cytological changes can be misinterpreted (9). 

Acute febrile interstitial pneumonitis occurred within less than 48 hours after the second to fourth cycles of chemotherapy (doxorubicin, cyclophosphamide, bleomycin, methotrexate, plus methylprednisolone) in five patients with non-Hodgkin s lymphoma who were receiving prophylactic G-CSF n — 3) or GM-CSF (n = 2) (23). Lymphocytic alveolitis was confirmed in four of these patients and all three patients tested had an increased number of CD8+ T cells. Even though all the patients received high-dose methylprednisolone, two died as a result of diffuse and extensive interstitial pulmonary fibrosis, demonstrated at postmortem. Although both G-CSF and GM-CSF can cause acute pneumonitis in patients with cancers, it is still unknown to what extent hemopoietic growth factors are involved in this complication. 

Excessive irradiation produces a pneumonitis and fibrosis thought to be caused by oxygen free-radical formation. Evidence for synergistic toxicity with radiation exists for bleomycin, busulfan, and mitomycin. Hyperoxia has shown synergistic toxicity with bleomycin, cyclophosphamide, and mitomycin. Carmustine, mitomycin, cyclophosphamide, bleomycin, and methotrexate all appear to show increased lung toxicity when they are part of multiple-drug regimens. 

Bleomycin (CCS) Complexes with Fe and 02 —> DNA strand scission (G2 phase) Hodgkin s, testicular, head, neck, skin CA Pneumonitis, pulmonary fibrosis, mucocutaneous reactions (blisters), alopecia, hypersensitivity... 

Bleomycin Acute pneumonitis, fibrosis, bronchiohtis Sulindac see NSAlDs... 

Toxicity The toxicity profile of bleomycin includes pulmonary dysfunction (pneumonitis, fibrosis), which develops slowly and is dose-limiting. H)q)ersensitivity reactions (chills, fever, anaphylaxis) are common, as are mucocutaneous reactions (alopecia, blister-formation, hyperkeratosis). 

Bleomycin Pneumonitis, pulmonary fibrosis, hyperpigmentation, alopecia, marrow-sparing ... 

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. ... 

Five patients treated with bleomyein, exposed to oxygen eoneentrations of 35 to 42% during and immediately following anaesthesia, developed a severe respiratory distress syndrome and died. Bleomycin-indueed pneumonitis and lung fibrosis were diagnosed at post-mortem. Another group of 12 matched patients who underwent the same procedures but with lower oxygen concentrations (22 to 25%) had an uneventful postoperative course. ... 

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. ... 

There is one report in the literature of a reversible penile calcification developing in a patient with lymphoma during treatment with bleomycin (30). Soft tissue calcifications paralleled, the course of presumed bleomycin-induced pneumonitis, suggesting a possible relation to the administration of the drug. 

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