Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighteen patients with refractory malignancies were treated with escalating doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and autologous bone marrow transplants (BMTX). Hematopoietic recovery was similar with doses of 300mg/m2qd X 3 and 500mg/m2qd X 3 providing suggestive evidence of a myeloprotective effect of the BMTX. Extramedullary toxicity was sporadic but occasionally severe; pulmonary fibrosis and severe cholestatic jaundice were seen in one case each. Antitumor responses were noted in patients with brain tumors, melanoma, hematological neoplasms and lung cancer.
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PMID:Intensive 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) autologous bone marrow transplantation therapy of refractory cancer: a preliminary report. 40 Jun 99

A 43-year-old man with metastatic malignant melanoma was treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in combination with imidazole carboxamide and hydroxyurea. He achieved complete remission. After 22 months of chemotherapy, the patient developed bilateral pulmonary infiltrates. Open lung biopsy showed sclerosing alveolitis. Long-term therapy with BCNU may cause pulmonary fibrosis, as has been seen with other cytotoxic drugs.
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PMID:Pulmonary fibrosis after prolonged therapy with 1,3-bis (2-chloroethyl)-1-nitrosourea. 89 Dec 93

The systemic administration of O,S,S-trimethyl phosphorodithioate (OSS), a contaminant of various organophosphorus insecticides, induces delayed damage to rat and mouse lung tissue. The lesion, particularly in the rat, closely resembles that produced by butylated hydroxytoluene (BHT) in mice. Although the time course of cell damage and repair has been studied in both species, it is not clear whether excess collagen, indicative of fibrosis, is deposited. Changes in pulmonary hydroxyproline content and synthesis, indices of collagen metabolism, were analysed in mice treated with 45 mg/kg OSS. A significant increase in total lung hydroxyproline was evident 21 days after treatment compared to both pair-fed and ad libitum controls. This increase was not augmented by subsequent treatment with 35 mg/kg 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or exposure to 70% oxygen for 7 days. The rate at which lung tissue synthesized hydroxyproline was increased 7-14 days after treatment with OSS. These data demonstrate that treatment of mice with OSS results in changes indicative of pulmonary fibrosis. However, in contrast to some other lung-toxic chemicals, this lesion was not enhanced by subsequent treatment with BCNU or hyperoxia.
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PMID:Pulmonary hydroxyproline content and production following treatment of mice with O,S,S-trimethyl phosphorodithioate. 366 Apr 35

The pathology of pulmonary toxicity induced by the anticancer drug 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was studied in F344 rats. The compound was administered in a multiple-dose regimen comparable to the dose schedule commonly given patients. Morphological aspects were investigated by light and electron microscopy in a serial sacrifice experiment. All animals developed pulmonary fibrosis accompanied by formation of peribronchial and peribronchiolar foci of granulomatous tissue. The first morphologically detectable changes were identified in alveolar type II cells and were suggestive of disturbed surfactant synthesis. Endothelial damage accompanied by pronounced plasma cell infiltration developed subsequently and was followed by the development of diffuse interstitial fibrosis.
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PMID:Sequential pathological changes induced in rats with the anti-cancer drug I, 3-bis (2-chloroethyl)-I-nitrosourea (BCNU). 407 57

A pediatric patient is reported who experienced fatal progressive pulmonary fibrosis as a complication of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) therapy. The patient received a cumulative dosage of 1.29 g (1.72 g/m2) over a two-year period as adjuvant therapy for a medulloblastoma. Two and one-half years after cessation of therapy, cough, tachypnea and fatigue were noted. Progressive pulmonary insufficiency developed. Pulmonary pathologic findings included interstitial fibrosis and alveolar dysplasia. Other cases of BCNU pulmonary toxicity are cited from the medical literature.
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PMID:Pulmonary fibrosis: a complication of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) therapy. 727 34

The North American Brain Tumor Consortium conducted a phase I trial of the combination 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide. Eligibility included a patient with a cancer type that was considered refractory to standard therapy. Prior nitrosourea treatments were not permitted. There were parallel dose escalations in two treatment schedules. Forty-five patients were enrolled during an 18-month period. The maximum tolerated doses (MTDs) when temozolomide followed BCNU (Arm A) were temozolomide at 550 mg/m2/p.o. and BCNU at 150 mg/m2/i.v.), whereas the MTD when temozolomide preceded BCNU (Arm B) was temozolomide at 400 mg/m2/p.o. and BCNU at 100 mg/m2/i.v. Toxicity was predominantly hematologic, although there were three instances of pulmonary toxicity, which in one case could have represented potentiation of nitrosourea-induced pulmonary fibrosis. The half-life of temozolomide was 1.86 (+/-0.31) h. There was a moderate relationship between dose and peak concentration and a strong relationship between dose and plasma concentration time curve. Pharmacokinetic parameters of temozolomide were unaffected by the treatment schedule, so the difference in MTD between the schedules is likely due to a biologic rather than a pharmacokinetic sequence interaction. There were 9 partial responses among 43 patients evaluable for response, including 5 of 25 with a histologic diagnosis of glioblastoma. The recommended dose and schedule for phase II trials of this regimen are BCNU 150 mg/m2/i.v. followed in 2 h by temozolomide 550 mg/m2/p.o. repeated every 6 weeks. We are also recommending screening and periodic pulmonary function testing during treatment to assess the possible potentiation of nitrosourea-induced pulmonary fibrosis.
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PMID:A phase I trial of 1,3-bis(2-chloroethyl)-1-nitrosourea plus temozolomide: a North American Brain Tumor Consortium study. 1130 52