title: Poor prognosis nonseminomatous germ-cell tumours (NSGCTs): should chemotherapy doses be reduced at first cycle to prevent acute respiratory distress syndrome in patients with multiple lung metastases?
abstract: BACKGROUND
  Patients with extensive lung metastases from nonseminomatous germ-cell tumours (NSGCTs) and dyspnoea at presentation are at high risk of acute respiratory distress syndrome (ARDS) and death within the first weeks after chemotherapy induction. This syndrome is linked to acute intra-alveolar haemorrhage related to early tumour necrosis, which in turn, can be complicated by pulmonary infection promoted by neutropenia. The management of these patients was modified at Institut Gustave Roussy in 1997 to try to avoid this complication.
  
  
  METHODS
  Data concerning all patients with lung metastases from NSGCT and dyspnoea or a partial pressure of oxygen (pO(2)) <80 mmHg treated from 1980 to 2006 in our institution were collected. Patients were treated in a specialised intensive care unit. From 1980 to 1997, the first chemotherapy cycle consisted in a full-dose regimen. After 1997, a 3-day reduced induction regimen of EP (cisplatin 20 mg/m(2)/day and etoposide 100 mg/m(2)/day) was used, with bleomycin and two additional days of EP being postponed to day 15, with the regular BEP regimen being started at day 21.
  
  
  RESULTS
  Twenty-five patients with poor-risk disseminated NSGCT according to the International Germ Cell Consensus Classification Group had extensive lung metastases plus dyspnoea at presentation (n = 6), a pO(2) <80 mmHg (n = 2), or both criteria (n = 17). Median human chorionic gonadotrophin was 200 000 UI (range 11-8 920 000), and 18 of 25 (72%) patients also had nonpulmonary visceral metastases. During the 1980-1997 period, 13 of 15 patients (87%) developed ARDS, 10 of whom died, and only 4 of 15 (27%) patients were long-term survivors. In contrast, during the 1997-2006 period, only 3 of 10 patients (30%) developed ARDS (P = 0.01), 2 of whom died, and 4 of 10 (40%) eventually survived.
  
  
  CONCLUSIONS
  Initial reduction of chemotherapy doses during the first cycle of chemotherapy for poor prognosis NSGCT with extensive lung metastases seems to prevent the risk of early death due to ARDS.
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif; University of Paris XI, Kremlin Bicêtre.
authors.forename: C
authors.initials: C
authors.lastname: Massard
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif; University of Paris XI, Kremlin Bicêtre.
authors.forename: A
authors.initials: A
authors.lastname: Plantade
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif; University of Paris XI, Kremlin Bicêtre.
authors.forename: M
authors.initials: M
authors.lastname: Gross-Goupil
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif; University of Paris XI, Kremlin Bicêtre.
authors.forename: Y
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif; University of Paris XI, Kremlin Bicêtre.
authors.forename: B
authors.initials: B
authors.lastname: Besse
authors.affiliation: Intensive Care Unit, Institut Gustave Roussy, Villejuif, France.
authors.forename: B
authors.initials: B
authors.lastname: Raynard
authors.affiliation: Intensive Care Unit, Institut Gustave Roussy, Villejuif, France.
authors.forename: F
authors.initials: F
authors.lastname: Blot
authors.affiliation: Intensive Care Unit, Institut Gustave Roussy, Villejuif, France.
authors.forename: S
authors.initials: S
authors.lastname: Antoun
authors.affiliation: Intensive Care Unit, Institut Gustave Roussy, Villejuif, France.
authors.forename: G
authors.initials: G
authors.lastname: Nitenberg
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif; University of Paris XI, Kremlin Bicêtre.
authors.forename: B
authors.initials: B
authors.lastname: Escudier
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif; University of Paris XI, Kremlin Bicêtre. Electronic address: fizazi@igr.fr.
authors.forename: K
authors.initials: K
authors.lastname: Fizazi
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000556:secondary*; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy