Netherlands Journal

netherlands journal of critical care
Copyright ©2006, Nederlandse Vereniging voor Intensive Care. All Rights Reserved. Received June 2006; accepted September 2006
c a s e r e p o r t
Polychemotherapy with bleomycin for metastasized
choriocarcinoma of the testis in a ventilated patient
M. de Bruin 1 , T. Müller, N. Foudraine 1 , S. Wouda 3 , P. ter Horst 2 , F. Nooteboom 4
1 Department of Intensive Care, 2 Department of Clinical Pharmacy, 3 Department of Pathology,
VieCuri Medisch Centrum voor Noord-Limburg, The Netherlands
4 Department of Intensive Care, Laurentius ziekenhuis Roermond, Roermond, The Netherlands
Key words: Bleomycin – Mechanical ventilation - Pulmonary fibrosis - Chemotherapy - Choriocarcinoma
Abstract. A 25 year-old Caucasian male was admitted to the ICU with respiratory failure after one cycle of BEP (45 International
Units (IU) (=30 mg) bleomycin, 200 mg etoposide and 40 mg cisplatin) chemotherapy. He had pulmonary metastases from stage
IV choriocarcinoma and was given the first BEP cycle while on a non-rebreathing mask (FiO 2 = 60%). Chemotherapy was continued
during mechanical ventilation. He developed end-stage pulmonary fibrosis after the fourth cycle with a cumulative dosage of
180 IU (120 mg) bleomycin and died on the 38 th day after his admission to the ICU. Post-mortem examination revealed no active
metastases in the lungs but extensive pulmonary fibrosis, probably secondary to administration of bleomycin. This case history
illustrates that standard chemotherapy including bleomycin is potentially lethal. Bleomycin treatment should be stopped in
patients who develop acute pulmonary toxicity and respiratory failure.
Introduction
Germ cell tumours originating in the testis can be grouped according
to prognosis. Choriocarcinoma, a non-seminomatous germ cell
cancer (NSGCC), is very rare in its pure form and by definition its
prognosis can be classified as poor risk. Additionally, even in better-risk
histological entities, poor risk is recognized in metastasized
NSGCC if pulmonary metastases exceed 20 in number[1], are present
outside the lungs (brain, liver or bone marrow) or the human
chorionic gonadotropin (HCG) tumour marker is elevated beyond
10.000 IU/ml [2]. The role of bleomycin in standard polychemotherapy
regimens for poor risk patients has been established as cure
rates have increased from 40% to 60 %[2]. Our patient had both
histologically confirmed NSGCC and advanced disease with more
than 40 pulmonary metastases and total HCG exceeding 800.000
IU/L. He was treated with the standard four-cycle BEP regimen [ 1,2]
for advanced disease as established by the Indiana group [2] and
the results of EORTC/MRC protocol 30974[6]. Bleomycin, antineoplastic
amide, first extracted from Streptomyces vertillicus by Umezawa
and colleagues in the 1960s, is known to have side effects including
interstitial pneumonitis and pulmonary fibrosis[1]. Little is known
about the administration of bleomycin to the critically ill, who are
frequently ventilated with high oxygen fractions.
We present a patient who was treated in accordance with standard
polychemotherapy regimen for advanced disease [1,2,3,4]. This
included bleomycin, etoposide and cisplatin (PEB) for grossly disseminated
choriocarcinoma (HCG above 800.000 IU/l) at the same
time as being treated with high oxygen fractions. Bleomycin may
have contributed to the fatal outcome for this patient.
Case report
A 25 year-old Caucasian male was admitted to our hospital in respiratory
distress. His medical history had been unremarkable up to
Correspondence:
Martha de Bruin
E-mail: marthadebruin@viecuri.nl
that point, when he developed back pain, shortness of breath, bloodtinged
sputum and night sweats. A chest X-ray showed bilateral
interstitial lung defects. Bronchoscopy was performed but was unremarkable.
Computed tomography of the thorax showed extensive
(more than 30) dense, coin-shaped lesions in both lungs, measuring
up to 4x5x2 cm each (Figure 1), with a bulky retroperitoneal tumour
measuring 20x12x10 cm. The differential diagnosis included sarcoidosis,
tuberculosis, yeast infection and metastases from testicular
carcinoma. A thoracotomy and open lung biopsy revealed a stage
IV,grossly metastasized, choriocarcinoma but no evidence of further
intrinsic lung pathology (Fig. 2). Serum tumour markers, measured
for the first time following thoracotomy, and GFR are shown in Table
1. Polychemotherapy following EORTC guidelines and comprising
the BEP scheme with 45 IU bleomycin (30 mg), etoposide (200 mg)
and cisplatin (40 mg) was initiated on the second postoperative day.
On the sixth postoperative day, four days after his first cycle of BEP,
he developed severe respiratory insufficiency (Table 1).
The patient was sedated, relaxed, intubated and mechanically
ventilated. His APACHE II score on ICU admission was 22. Pressure
controlled ventilation with 30 cm H 2 O and 14 cm H 2 O of PEEP
and a FiO 2 of 60% resulted in a p a O 2 7.3 kPa (p a O 2 /FiO 2 = 12.2).
In order to maximize the chance of cure, BEP chemotherapy was
continued by means of non-bolus infusion on ICU days 4, 12 and
19, totalling 180 IU (120 mg) bleomycin. Markers (AFP, ß-HCG)
decreased significantly (Table 1) chemotherapy. The clinical course
of the patient, however, involved multiple and severe complications
including a pneumothorax treated by chest tube insertion on ICU
day six, severe exudative pericarditis treated with pericardiocentesis
on ICU day twelve, and fever thereafter. Bronchial secretion cultures
revealed Candida spec., E. coli, Enterococcus faecalis and Stenotrophomonas
maltophilia which were treated with intravenous and oral antibiotics
according to pattern of resistance. Persistent leucopenia with a nadir
of 0.9*10 9 leucocytes /l meant the patient had to be put in isolation
for his protection on day 29. His worsening respiratory and clinical
condition necessitated pressure-controlled ventilation with peak
pressures of 66 cm H 2 0 (including up to 8 cm H 2 O PEEP) and a FiO 2
538 neth j crit care • volume 10 • no 5 • october 2006