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HPI
 49
year old woman with metastatic
breast cancer seen in the hospital
for fever and SOB
 Right
breast cancer (infiltrating
ductal ca) diagnosed in 2001 at
age 38
– Treatment included mastectomy
(negative lymph nodes),
doxarubicin and cytoxan (4 courses)
HPI
 Patient
did well until March 2010
when erythema over right
chest noted
– Biopsy + adenoca c/w breast
 Breast
ca: “triple negative”
– Estrogen receptors
– Progesterone receptors
– Her2
Staging
 PET
scan demonstrated
multiple positive lymph
nodes: mediastinum,
supraclavicular and bone
mets
Treatment Course
 Radiation
 June
to chest wall
2010
– Received Paclitaxel and Bevacizumab
– Also given Zometa for bone mets
– Stopped in Dec 2010 due to toxicity
 April
2011
– Started Gemcitabine/Carboplatin and
Iniparib (experimental protocol)
Treatment Course
 October
2011
– Brain mets noted and patient started
stereotactic brain radiation, also given
dexamethasone
 Dexamethasone
mid-December
 December
stopped in
27, 2011
– Admitted with fever and SOB
PMH/FH/SH/Meds
 Prothrombin
mutation noted on
initial heme eval - prophylactically
started on warfarin in 2010
 Family
history of breast CA
 Non-smoker,
 Meds:
no unusual exposures
omeprazole, metoprolol,
warfarin
Physical Exam/Lab
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VS
– Current temp 37 (prior to 37.9)
– Pulse 110
– On 02 3 LPM
Chest: Bilateral crackles,
most prominent at bases
No other physical findings
H/H 11.8/33.9
WBC 5.1
Plt 64
INR 1.58
ESR >100
CRP 213
CT Chest - Radiology
 Diffuse
groundglass opacities and
scattered centrilobular nodules.
Differential includes cardiogenic or
noncardiogenic pulmonary edema,
infection and drug reaction.
Clinical Course
 Started
on antibiotics
(Zosyn, Levaquin)
 Negative:
cocci serology, PCR
of nasal swab for influenza and
mycoplasma antibodies
 Bronchoscopy
on 12/29
with BAL done
BAL
 Fluid
slightly hemorrhagic,
did not clear with repeated lavage
 Smears/cultures
negative
 Negative
aspergillus antibody in BAL
 Negative
PCR for PCP and legionella
Clinical Course
 Patient
continued to have
low-grade fever
–Oxygen requirements increased
 BAL
cultures remained negative
 VATS
lung biopsy done on 1/5/12
–? infection
–? drug toxicity
Pathology Report
 Fibrinous
acute lung injury with
increased alveolar macrophages,
scattered multinucleated giant cells
and increased extravascular tissue
eosinophils. The overall
histopathology favors drug toxicity
over other possibilities.
Clinical Course
 Patient
started on corticosteroid
therapy
 All
cultures remained negative
 Was
discharged on 1/7/12 on
prednisone 60 mg/day
 F/U
in pulmonary clinic on 2/8/12
– Clinically improved
Clinical Diagnosis: Drug-induced Lung
Injury – Likely due to Gemcitabine
 Patient
most recently receiving
gemcitabine/carboplatin/iniparib
 Onset
of respiratory symptoms was
delayed several months after last
dose – delay due to dexamethasone
treatment for brain mets?
Gemcitabine Lung Toxicity

Acute dyspnea with infusion in 10%

3 types of acute pneumonitis:
– Capillary leak syndrome
– Diffuse alveolar damage
– Alveolar hemorrhage

Frequency is low: 0.27%
Gemcitabine Lung Toxicity
Reduction in DLco within 2 months
of treatment reported in 24%, often
self-limited (more frequent in
women, older age, low baseline
DLco)
 Some cases of pulmonary fibrosis
reported, but rare

Ann Onc 2004
Gemcitabine Lung Toxicity
 Factors
increasing risk of lung injury
include other chemotherapy
(including paclitaxel), chest radiation
 Mortality
rate with acute pneumonitis
up to 20%, but rapid response to
steroid therapy is reported
Iniparib
Poly(adenosine diphoshate-ribose)
polymerase inhibitor (PARP)
 Recent phase 2 trial (NEJM,
2011;364:205) in metastatic “triple
negative” breast cancer
 123 patients given iniparib with or without
gemcitabine/carboplatin
 Iniparib improved survival: 7.7 months vs
12.3 months
 Dyspnea reported, but no severe
pulmonary complications from Iniparib in
this study.
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