HPI u 49 year old woman with metastatic
- Slides: 30
HPI u 49 year old woman with metastatic breast cancer seen in the hospital for fever and SOB u Right breast cancer (infiltrating ductal ca) diagnosed in 2001 at age 38 – Treatment included mastectomy (negative lymph nodes), doxarubicin and cytoxan (4 courses)
HPI u Patient did well until March 2010 when erythema over right chest noted – Biopsy + adenoca c/w breast u Breast ca: “triple negative” – Estrogen receptors – Progesterone receptors – Her 2
Staging u PET scan demonstrated multiple positive lymph nodes: mediastinum, supraclavicular and bone mets
Treatment Course u Radiation u June to chest wall 2010 – Received Paclitaxel and Bevacizumab – Also given Zometa for bone mets – Stopped in Dec 2010 due to toxicity u April 2011 – Started Gemcitabine/Carboplatin and Iniparib (experimental protocol)
Treatment Course u October 2011 – Brain mets noted and patient started stereotactic brain radiation, also given dexamethasone u Dexamethasone mid-December u December stopped in 27, 2011 – Admitted with fever and SOB
PMH/FH/SH/Meds u Prothrombin mutation noted on initial heme eval - prophylactically started on warfarin in 2010 u Family history of breast CA u Non-smoker, u Meds: no unusual exposures omeprazole, metoprolol, warfarin
Physical Exam/Lab u u u u u 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 u Diffuse groundglass opacities and scattered centrilobular nodules. Differential includes cardiogenic or noncardiogenic pulmonary edema, infection and drug reaction.
Clinical Course u Started on antibiotics (Zosyn, Levaquin) u Negative: cocci serology, PCR of nasal swab for influenza and mycoplasma antibodies u Bronchoscopy on 12/29 with BAL done
BAL u Fluid slightly hemorrhagic, did not clear with repeated lavage u Smears/cultures negative u Negative aspergillus antibody in u Negative PCR for PCP and legionella BAL
Clinical Course u Patient continued to have low-grade fever – Oxygen requirements increased u BAL cultures remained negative u VATS lung biopsy done on 1/5/12 – ? infection – ? drug toxicity
Pathology Report u 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 u Patient started on corticosteroid therapy u All cultures remained negative u Was discharged on 1/7/12 on prednisone 60 mg/day u F/U in pulmonary clinic on 2/8/12 – Clinically improved
Clinical Diagnosis: Drug-induced Lung Injury – Likely due to Gemcitabine u Patient most recently receiving gemcitabine/carboplatin/iniparib u Onset of respiratory symptoms was delayed several months after last dose – delay due to dexamethasone treatment for brain mets?
Gemcitabine Lung Toxicity u Acute dyspnea with infusion in 10% u 3 types of acute pneumonitis: – Capillary leak syndrome – Diffuse alveolar damage – Alveolar hemorrhage u 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) u Some cases of pulmonary fibrosis reported, but rare u Ann Onc 2004
Gemcitabine Lung Toxicity u Factors increasing risk of lung injury include other chemotherapy (including paclitaxel), chest radiation u Mortality rate with acute pneumonitis up to 20%, but rapid response to steroid therapy is reported
Iniparib Poly(adenosine diphoshate-ribose) polymerase inhibitor (PARP) u Recent phase 2 trial (NEJM, 2011; 364: 205) in metastatic “triple negative” breast cancer u 123 patients given iniparib with or without gemcitabine/carboplatin u Iniparib improved survival: 7. 7 months vs 12. 3 months u Dyspnea reported, but no severe pulmonary complications from Iniparib in this study. u
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