Fatal bleomycin pulmonary toxicity in the west of Scotland 1991-95: a review of patients with germ cell tumours

Bandak

et al. 2013

Cancer

BACKGROUND: Germ-cell cancer (GCC) patients aged 40 years have a two-fold higher GCC-specific mortality. It has been hypothesized that reduced treatment intensity combined with increased treatment related toxicity could be the explanation. The objective was to analyze chemotherapy intensity, treatment related toxicity and survival in patients aged 40 years treated with standard chemotherapy for GCC compared with a younger control group that received similar treatment during the same period. METHODS: From 1984 to 2011, 135 patients aged 40 years with disseminated GCC treated with bleomycin, etoposide and cisplatin (BEP). A control-group of 135 patients aged 18-35 years was randomly selected matched on year of BEP treatment. Cumulated doses of BEP as well as bone marrow toxicity, renal-and lung functions were recorded before, during and after termination of treatment. All patients were followed until death or October 1, 2011. RESULTS: The cumulated doses of BEP were comparable between the two groups, however, more patients aged 40 years were reduced in bleomycin doses based on a decrease in carbon monoxide diffusion capacity corrected for haemoglobin (P 5 0.03). No differences between the two groups were found regarding bone marrow toxicity or mean percentage changes in lung-or renal function. Patients aged 40 year had increased cancer specific mortality, HR 5 4.8 (P 5 0.005). In particular patients with disease progression after first line chemotherapy had increased mortality (P 5 0.015). Moreover, the 5-year overall survival for patients aged 40 years was 82.5% compared to the expected 5-year survival of the background population of 96.3% (P <0.001). CONCLUSIONS: Treatment related toxicity could not explain the increased cancer specific mortality in patients aged 40 years compared to a younger control-group, and while there were no differences in the administrated doses of cisplatin/ etoposide, a decreased number of bleomycin doses were administered in the older patients. Apart from this, the inferior prognosis could be related to tumour biology, increased co-morbidity, or more severe toxicity in relation to second line treatment. Cancer 2014;120:43-51.

Section: Discussioncontrasting

confidence: 42%

Survival and toxicity in patients with disseminated germ cell cancer aged 40 years and older

Bandak

et al. 2013

Cancer

“…This type of pulmonary toxicity has extensively been studied and attributed to a majority of the pulmonotoxic antineoplastic agents, of which bleomycin is the prototype and nitrosoureas rank second [3][4][5][6][7]. Major concern with this pulmonary toxicity is the potential to progress to irreversible chronic pulmonary fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Noncardiogenic Pulmonary Edema: An Unusual and Serious Complication of Anticancer Therapy

Briasoulis

Pavlidis

2001

The Oncologist

Noncardiogenic pulmonary edema (NCPE) is a rare and less well-recognizable pulmonotoxic syndrome of anticancer therapy than pneumonitis/fibrosis. NCPE is a clinical syndrome characterized by simultaneous presence of severe hypoxemia, bilateral alveolar infiltrates on chest radiograph, and no evidence of left atrial hypertension/congestive heart failure. The diagnosis of drug-related NCPE relies upon documented exclusion of any infectious, metabolic, or cancer-related causes. The Oncologist 2001;6:153-161 www.TheOncologist.com Correspondence: Evangelos Briasoulis, M.D., Medical Oncology Department, Ioannina University, Ioannina, 45110, Greece. Telephone and Fax: 30-651-99394; e-mail: ebriasou@otenet.gr. Received August 15, 2000; accepted for publication November 30, 2000. ©AlphaMed Press 1083-7159/2001 INTRODUCTIONSeveral cancer therapeutic drugs are known to induce pulmonary damage, which may result in a variety of clinicopathologic syndromes with minor to severe clinical consequences [1]. Clinical syndromes associated with drug-induced pulmonary toxicity include pneumonitis/fibrosis, hypersensitivity lung disease, and noncardiogenic pulmonary edema (NCPE)/acute respiratory distress syndrome (ARDS). These syndromes share a similar symptomatology but differ in regard to the time-relation to cancer treatment, the radiographic findings, the duration of pulmonary damage, and the long-term outcome [2]. Non-specific symptomatology of cough, progressive dyspnea, and often a low-grade fever alert clinicians confronted with the diagnostic challenge to recognize subclinical syndromes and differentiate fully developed drug-induced pulmonary reactions from lung injuries caused by infectious, cardiac, and neoplastic causes.

International Journal of Oncology

“…7C), suggesting that BLH is not participating in bleomycin action in lung cells. According to the clinical reports, up to 46% of patients will develop pneumonitis and mortality rate is approximately 3% after administration of bleomycin (21,22), showing individual differences. Therefore, lower level of BLH is not a unique factor to determine the bleomycin-induced pulmonary fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Action of bleomycin is affected by bleomycin hydrolase but not by caveolin-1

Chen

2012

Abstract. Bleomycin is a first-line clinically used antitumor antibiotic for effective treatment of certain types of cancer in combination with other antitumor agents. Its action is affected by bleomycin hydrolase (BLH), DNA repair enzymes, membrane transport proteins and other cellular factors. To clarify whether BLH confers the resistance to bleomycin in tumor cells, it is necessary to further investigate the roles of BLH and its combination with other factors such as caveolin-1 in the action of bleomycin. In this study fourteen human cell lines were used for determination of bleomycin action and roles of BLH and caveolin-1. The relationship between action of bleomycin and cellular amount of BLH was detected by the MTT method and western blotting in the human leukemia cell line HL-60, HeLa cervical cancer cells and HaCaT immortalized keratinocyte cells. The sensitivity to bleomycin was increased in HeLa cells after knockdown of BLH mRNA by RNA interference. There is no relationship between caveolin-1 levels and action of bleomycin, although the distribution of the cell cycle was altered in the caveolin-1-knockdown HeLa cells after treatment with bleomycin. In addition, regulation of BLH and caveolin-1 expression in HeLa and HaCaT cells was observed in a concentration-dependent manner after exposure to bleomycin. In conclusion, bleomycin hydrolase is one of the biomarkers for determination of bleomycin action. Although caveolin-1 can respond to bleomycin treatment, it is unrelated to bleomycin sensitivity.