uterine cervical cancer is the most common malignancy of the female genital tract , and in 2002 accounted for 9.1% of total malignancies in korean women ( 1 ) . neoadjuvant chemotherapy ( nac ) based on cisplatin has been widely used as a therapeutic strategy to improve survival in locally advanced cervical cancer ( 2 - 4 ) . of the several available nac regimens , a quick ( at most three cycles ) course of vincristine , bleomycin , and cisplatin is to be preferred due to short duration . nac administered every 10 days has been tried and found to produce favorable results ( 5 , 6 ) . furthermore , bleomycin - induced pulmonary toxicity , one of the most fatal adverse effects , has been reported to be unusual after a quick course of nac - vbp ( 5 - 7 ) . however , we have experienced several fatal cases of pulmonary toxicity , at levels higher than those reported in the literature ( 5 - 10 ) , associated with a quick course of nac - vbp in patients with international federation of gynecology and obstetrics ( figo ) stage ib - iib cervical cancer . in the present study , we analyzed our experiences of radiologically and/or histologically confirmed pulmonary toxicity following a quick course of nac - vbp in cervical cancer . after obtaining the approval of the institutional review board of kyung hee university ( seoul ) , 61 patients who underwent a quick course of nac - vbp in figo stage ib - iib cervical cancer from 1995 to 2007 were retrospectively identified in the tumor registry databases at the department of obstetrics and gynecology . the nac schedule consisted of cisplatin 50 mg / m intravenous infusion on day 1 , vincristine 1 mg / m intravenous bolus on day 1 , and bleomycin 25 mg / m / day continuous intravenous infusion on days 1 to 3 . cycles were repeated every 10 days for a maximum of three cycles . prior to administering chemotherapy , complete medical assessments , including chest radiography , creatinine clearance , renal function , and pulmonary function testing ( pft ) , were performed . intensive work ups , such as , high - resolution computed tomography ( hr - ct ) with or without bronchoscopic biopsy , were performed in all cases with pulmonary symptoms or suspicious findings by chest radiography during or after nac - vbp . histopathologic slides were reviewed by pathologists at our institute with considerable experience of gynecologic malignancies and pulmonary disease . seven ( 11.5% ) of the 61 patients were identified to have pulmonary toxicity and 2 ( 3.3% ) succumbed due to progression of pulmonary fibrosis despite aggressive treatment and the adoption of a multidisciplinary approach . a comparison of the demographic factors of patients with and without pulmonary toxicity identified no significant differences in terms of age , parity , histologic type , or total bleomycin dose ( table 1 ) . pulmonary toxicity was first suspected based on clinical symptoms or routine chest - radiographic and/or pulmonary function test findings , and was subsequently confirmed by hr - ct with or without a bronchoscopic biopsy . three patients were completely asymptomatic in terms of respiratory symptoms but had suspicious chest radiographic findings . of the 4 symptomatic patients , 1 suffered from a fever and sputum production , and 3 complained of pulmonary symptoms such as dyspnea and/or cough . two of the 3 asymptomatic patients were closely observed and spontaneously improved , but 1 patient deteriorated gradually and eventually found it hard to breathe . she was treated with medication containing corticosteroid ( prednisolone 1 mg / kg / day ) . however , her symptom persisted , and thus , corticosteroid was continued at a reduced dose ( prednisolone 0.5 mg / kg / day ) . one patient with fever and sputum production improved on conservative management . in the 3 patients who complained of dyspnea and pulmonary symptoms , 1 improved on steroid therapy ( methylprednisolone 40 mg / day , followed by maintenance therapy methylprednisolone 10 mg / day ) . however , the other 2 patients deteriorated and pulmonary fibrosis progression despite steroid pulse therapy ( methylprednisolone 500 mg / day for 3 days ) and developed acute respiratory distress syndrome , which led to respiratory arrest and death in both within 1 month of diagnosing pulmonary toxicity . in these two patients , bronchiolitis obliterans organizing pneumonia ( boop ) or interstitial pneumonitis were characteristic chest hr - ct findings . these findings of boop were characterized by multifocal , patchy distributions of ground glass attenuation and consolidation , predominantly in the subpleural region , with partial bronchovascular bundle thickening and interlobular septal thickening by hr - ct ( fig . the presence of interstitial pneumonitis was demonstrated by diffuse extensive homogenous ground glass attenuation , which was more prominent in the subpleural region , intermixed with interlobular septal thickenings , bronchiectasis , and honeycomb cysts . these findings suggested diffuse alveolar damage or acute phases interstitial lung disease , such as , nonspecific interstitial pneumonia ( fig . 3 ) . furthermore , as a result of long term steroid use , steroid - induced diabetes mellitus requiring insulin therapy developed in two patients ( cases 2 and 5 ) . it remains unclear whether nac improves survival outcomes as compared with primary radical surgery or concurrent chemoradiation therapy in cervical cancer ( 7 , 9 , 12 - 14 ) . nevertheless , many gynecologic oncologists perform nac to reduce tumor volume and consequently to improve survival , based on clinician 's preference and the medical resources available , and thus , the usefulness of nac is probably beyond the scope of this study . rather , we focus on pulmonary toxicity , one of the most fatal adverse effects following a quick course of nac - vbp . pulmonary toxicity exacerbation by combination chemotherapy has already been reported upon ( 15 ) , and of several chemotherapeutic agents responsible , bleomycin has been identified as the most causative agent ( 16 ) . pulmonary toxicity is the most fatal adverse effect of bleomycin , and may occur in up to 46% of patients ( 17 , 18 ) , with a mortality rate , among those treated , of approximately 3% ( 19 , 20 ) . however , pulmonary toxicity is rare after a quick nac - vbp course , which is one of the most popular nac regimens used in cervical cancer ( 6 - 10 , 21 , 22 ) . table 3 itemizes publications on pulmonary toxicity after a quick course of nac - vbp in cervical cancer . the majority of series reported pulmonary toxicity in only 0 - 2% of the population studied , and that it occurred more frequently in elderly patients ( 5 , 21 ) . however , another study reported that a quick course of nac - vbp in cervical cancer was associated with significant pulmonary toxicity in 13.3% of cases ( 22 ) , which is similar to the present study . these findings stress that the possibility of pulmonary toxicity should be considered in patients receiving a quick course of nac - vbp . bleomycin is available in two forms , i.e. , as a sulfate and chlorohydrate . in the present study , we used bleomycin chlorohydrate which causes less pulmonary toxicity ( 5 , 21 ) . however , the mechanisms of bleomycin - induced pulmonary toxicity are not entirely understood , though several factors , including old age ( > 70 yr ) , a high cumulative dose , impaired renal function , administration route , smoking , granulocyte colony stimulating factor ( g - csf ) use , and multiple chemotherapeutics agents ( mainly cisplatin ) may increase its risk ( 17 ) . in the present study , all patients with pulmonary toxicity were nonsmokers and were confirmed to have normal renal function by creatinine clearance before each chemotherapy cycle . in addition , we found no evidence that age and cumulative bleomycin dose were significantly different for patients with / without pulmonary toxicity , and thus , we failed to identify any factor predisposing pulmonary toxicity . bleomycin - induced pulmonary toxicity may be reversible in cases with minimal alveolar change , but in its advanced state may progress to severe fibrosis and death ( 23 ) . moreover , although high doses of corticosteroids have been widely administered in cases of bleomycin - induced pulmonary toxicity , no standard therapy has been agreed . in addition , the efficacies of corticosteroids are unclear and the adverse effects of long term corticosteroid therapy , such as , steroidinduced diabetes mellitus may be grave ( 18 ) . we conclude fatal pulmonary toxicity is a major concern of quick nac - vbp regimens , and advise that special attention be taken to monitor for bleomycin - induced pulmonary toxicity .
pulmonary toxicity is one of the most serious adverse effects associated with a quick course of vincristine , bleomycin , and cisplatin neoadjuvant chemotherapy ( nac - vbp ) . 
 the aim of this study was to evaluate pulmonary toxicity related to a quick course nac - vbp . 
 a total of consecutive 61 patients , who underwent at most 3 cycles of nac - vbp every 10 days in the international federation of gynecology and obstetrics ( figo ) stage ib - iib cervical cancer from 1995 to 2007 , were retrospectively analyzed . 
 of the 61 study subjects , 7 ( 11.5% ) were identified to have pulmonary toxicity and 2 ( 3.3% ) died of pulmonary fibrosis progression despite aggressive treatment and the use of a multidisciplinary approach . 
 no factor predisposing pulmonary toxicity was identified . 
 initial symptoms were non - specific , but bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis were characteristic findings by high - resolution computed tomography of the chest . 
 the benefit of steroid therapy was uncertain and was associated with steroid - induced diabetes mellitus requiring insulin therapy in two patients . 
 fatal pulmonary toxicity is a major concern of a quick course nac - vbp . in conclusion 
 , these patients require special monitoring for bleomycin - induced pulmonary toxicity .