title: Pulmonary Function in Patients With Germ Cell Cancer Treated With Bleomycin, Etoposide, and Cisplatin.
abstract: For patients with germ cell cancer, various pulmonary toxicity risk factors have been hypothesized for treatment with bleomycin, etoposide, and cisplatin (BEP). Because existing studies have shortcomings, we present a large, unselected cohort of patients who have undergone close monitoring of lung function before, during, and after treatment with BEP to disclose valid pulmonary toxicity risk factors.
  
  
  
  All patients who were treated with BEP at Rigshospitalet, Copenhagen, Denmark, from 1984 to 2007, were included. Pulmonary function tests (PFTs) that measured the diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in 1 second, and forced vital capacity were performed systematically before, during, and after treatment with BEP for 5 years of follow-up. According to local protocol, bleomycin was discontinued if hemoglobin-corrected DLCO (DLCOc) decreased ≥ 25% compared with pretreatment value. Covariates of possible importance were evaluated with a multiple regression analysis for pretreatment PFTs and with a mixed model for follow-up PFTs. Bleomycin was adjusted on the basis of PFT results and was thus omitted as covariate.
  
  
  
  Overall, 565 patients were evaluated with a PFT before or after treatment with BEP. During BEP, 15 patients died of progressive disease or toxicity, including one patient from bleomycin-induced pneumonitis. Post-treatment DLCOc decreased significantly, with a rebound during follow-up. Forced expiratory volume in 1 second and forced vital capacity remained unchanged after BEP but increased significantly to levels above pretreatment during follow-up. International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic group, mediastinal primary, pulmonary metastases, and smoking all significantly influenced baseline PFT results. Pulmonary surgery, pulmonary embolism, IGCCCG poor prognosis, and smoking influenced PFT during follow-up. Mediastinal primary, pulmonary metastases, age, or doses of cisplatin and etoposide had no influence on follow-up PFT, and renal function did not influence PFT.
  
  
  
  After 5 years of follow-up, pulmonary impairment in patients with germ cell cancer who were treated with BEP was limited. Exceptions were patients treated with pulmonary surgery, those who suffered pulmonary embolism, and those in the IGCCCG poor prognostic group.
authors.affiliation: Jakob Lauritsen, Maria Gry Gundgaard Kier, Mikkel Bandak, Mette Saksø Mortensen, Frederik Birkebæk Thomsen, Jann Mortensen, and Gedske Daugaard, Rigshospitalet; and Maria Gry Gundgaard Kier, Danish Cancer Society, Copenhagen, Denmark. jakob.lauritsen@regionh.dk.
authors.forename: Jakob
authors.initials: J
authors.lastname: Lauritsen
authors.affiliation: Jakob Lauritsen, Maria Gry Gundgaard Kier, Mikkel Bandak, Mette Saksø Mortensen, Frederik Birkebæk Thomsen, Jann Mortensen, and Gedske Daugaard, Rigshospitalet; and Maria Gry Gundgaard Kier, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Maria Gry Gundgaard
authors.initials: MG
authors.lastname: Kier
authors.affiliation: Jakob Lauritsen, Maria Gry Gundgaard Kier, Mikkel Bandak, Mette Saksø Mortensen, Frederik Birkebæk Thomsen, Jann Mortensen, and Gedske Daugaard, Rigshospitalet; and Maria Gry Gundgaard Kier, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Bandak
authors.affiliation: Jakob Lauritsen, Maria Gry Gundgaard Kier, Mikkel Bandak, Mette Saksø Mortensen, Frederik Birkebæk Thomsen, Jann Mortensen, and Gedske Daugaard, Rigshospitalet; and Maria Gry Gundgaard Kier, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Mette Saksø
authors.initials: MS
authors.lastname: Mortensen
authors.affiliation: Jakob Lauritsen, Maria Gry Gundgaard Kier, Mikkel Bandak, Mette Saksø Mortensen, Frederik Birkebæk Thomsen, Jann Mortensen, and Gedske Daugaard, Rigshospitalet; and Maria Gry Gundgaard Kier, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Frederik Birkebæk
authors.initials: FB
authors.lastname: Thomsen
authors.affiliation: Jakob Lauritsen, Maria Gry Gundgaard Kier, Mikkel Bandak, Mette Saksø Mortensen, Frederik Birkebæk Thomsen, Jann Mortensen, and Gedske Daugaard, Rigshospitalet; and Maria Gry Gundgaard Kier, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Jann
authors.initials: J
authors.lastname: Mortensen
authors.affiliation: Jakob Lauritsen, Maria Gry Gundgaard Kier, Mikkel Bandak, Mette Saksø Mortensen, Frederik Birkebæk Thomsen, Jann Mortensen, and Gedske Daugaard, Rigshospitalet; and Maria Gry Gundgaard Kier, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Gedske
authors.initials: G
authors.lastname: Daugaard
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D012042:Registries; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*
chemical_list: D001761:Bleomycin; D005047:Etoposide; D002945:Cisplatin