Q5 Oncology RNSH 2003
Which drug is most likely to cause respiratory distress?
a) Bleomycin
b) Buslphan
c) ATRA
d) Gemcitabine
e) Cyclophosphamide
Bleomycin is an antitumor antibiotic isolated from a strain of Streptomyces verticillus in 1966. The drug has been used successfully to treat a variety of tumors, including squamous cell carcinoma of the head and neck, cervix, and esophagus, as well as germ cell tumors and Hodgkin's and non-Hodgkin's lymphomas.
The major limitation of bleomycin therapy is the potential for developing a life-threatening pneumonitis that is dose- and time-dependent and can progress to interstitial pulmonary fibrosis in up to 10 percent of patients receiving the drug. Other forms of lung injury, such as hypersensitivity pneumonitis and nodular pulmonary densities, also have been reported less commonly.
Busulfan is an alkylating agent that is almost exclusively used in the treatment of chronic granulocytic leukemia. The drug is also administered in higher doses as part of preparative regimens prior to bone marrow transplantation. The principal side effect is myelosuppression, but the drug is usually well tolerated.
Busulfan was the first cytotoxic drug reportedly associated with pulmonary toxicity. Symptomatic pulmonary injury is estimated to occur in fewer than five percent of patients (children and adults). Subclinical lung damage, however, may develop in a considerably higher number of those exposed to the drug.
ATRA (All-trans retinoic acid) - Acute promyelocytic leukemia (APL): Induction of remission in patients with APL, French American British (FAB) classification M3 (including the M3 variant), characterized by the presence of the t(15;17) translocation or the presence of the PML/RARalpha gene who are refractory to or who have relapsed from anthracycline chemotherapy, or for whom anthracycline-based chemotherapy is contraindicated.
About 25% of patients with APL, who have been treated with tretinoin, have experienced a syndrome called the retinoic acid-APL (RA-APL) syndrome which is characterized by fever, dyspnea, weight gain, radiographic pulmonary infiltrates and pleural or pericardial effusions. This syndrome has occasionally been accompanied by impaired myocardial contractility and episodic hypotension. It has been observed with or without concomitant leukocytosis. Endotracheal intubation and mechanical ventilation have been required in some cases due to progressive hypoxemia, and several patients have expired with multiorgan failure. The syndrome usually occurs during the first month of treatment, with some cases reported following the first dose.
Gemcitabine - Adenocarcinoma of the pancreas; first-line therapy for patients with locally advanced (nonresectable stage II or stage III) or metastatic (stage IV) adenocarcinoma of the pancreas (indicated for patients previously treated with 5-FU); combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (stage IIIA or IIIB) or metastatic (stage IV) nonsmall-cell lung cancer.
Gemcitabine can suppress bone marrow function manifested by leukopenia, thrombocytopenia and anemia, and myelosuppression is usually the dose-limiting ototoxicity. The incidence of fever is 41% and gemcitabine may cause fever in the absence of clinical infection. Rash has been reported in 30% of patients - typically a macular or finely granular maculopapular pruritic eruption of mild to moderate severity involving the trunk and extremities. Gemcitabine should be used with caution in patients with pre-existing renal impairment (mild proteinuria and hematuria were commonly reported; hemolytic uremic syndrome has been reported) and hepatic impairment (associated with transient elevations of serum transaminases in 2/3 of patients - but no evidence of increasing hepatic toxicity).
Cyclophosphamide is an immunosuppressive alkylating agent that is used in combination with other chemotherapeutic agents for the treatment of a variety of malignant processes. It is also increasingly used for the treatment of certain autoimmune diseases, either as a sole agent or in combination with corticosteroids. Unfortunately, long-term use of cyclophosphamide is associated with a multitude of significant side effects, such as hair loss, leukopenia, hemorrhagic cystitis, infertility, the development of secondary malignancies, and pulmonary toxicity.
Cyclophosphamide-induced pulmonary injury appears to be rare. There are two distinct clinical patterns of pulmonary toxicity associated with cyclophosphamide: an acute pneumonitis that occurs early in the course of treatment; and a chronic, progressive, fibrotic process that may occur after prolonged therapy