Recommandé
Contenu connexe
Tendances
Tendances (20)
En vedette
En vedette (7)
Similaire à Pulmonary toxicity by cystostatics
Similaire à Pulmonary toxicity by cystostatics (20)
Plus de Jordi Roig
Plus de Jordi Roig (8)
Dernier
Dernier (20)
Pulmonary toxicity by cystostatics
- 1. Pulmonary toxicity caused by cytotoxic drugs DR. J. ROIG CUTILLAS HOSPITAL NOSTRA SRA. MERITXELL ANDORRA
- 2. Alkylating agents Cyclophosphamide, nitrosureas, ifosfamide, procarbazine, busulfan, melphalan, chlorambucil Antimetabolites Methrotrexate, gemcitabine, azathioprine, 6-mercaptopurine, cytosine arabinoside, fludarabine Antibiotics Mitomycin, doxorubicin, bleomycin, neocarzinostatin Antimicrotubule agents Vinca alkaloids Taxanes: paclitaxel, docetaxel Miscellaneous Topotecan, irinotecan Etoposide, teniposide Gefitinib, ATRA, arsenic trioxide Chemotherapeutic agents and pulmonary toxicity Roig J et al. Clin Pulm Med 2006
- 3. Chemoterapy-induced lung toxicity: differential diagnosis • Pulmonary infection • Malignancy-related thromboembolism • Local tumor progression • Iatrogenic diffuse alveolar hemorrhage • Radiation-induced pneumonitis • O2, transfusion, other drug-induced toxicity • Postoperative complications
- 4. Chemoterapy-induced lung toxicity: clinical clues • Time course & high index of suspicion • Not distinctive features; sometimes fever • Subacute or even abrupt onset are possible • X-ray lags behind clinical symptoms: CT • Decreased DLCO: early marker & monitor • Increased DLCO: diffuse alveolar bleeding • Nonspecific imbalance of CD4/CD8 (BAL)
- 5. Chemotherapy-induced lung toxicity: role of other factors • Biological response modifiers • Hormonal agents • Other agents: www.pneumotox.com • Interactions with radiotherapy • Interactions in combination chemotherapy • Thoracic surgery following chemotherapy
- 6. Chemotherapeutic agents used in lung cancer that may cause acute pneumonitis Cyclophosphamide Docetaxel Etoposide Gemcitabine Ifosfamide Ipomeanol Irinotecan Methotrexate Mitomycin Paclitaxel Procarbazine Vinca alkaloids
- 7. Tissue Reactions in Chemotherapy-induced Pulmonary Toxicity Chronic interstitial pneumonia Diffuse alveolar damage – Acute interstitial pneumonia Bronchiolitis obliterans organizing pneumonia (BOOP) Obliterative bronchiolitis Hypersensitivity pneumoniaa Lung fibrosis Pulmonary edema Pulmonary hemorrhage Pulmonary hypertension Pulmonary veno-occlusive disease a Poorly formed granulomas in methotrexate lung toxicity
- 8. Chemotherapeutic agents used in lung cancer that may cause ADRS Gemcitabine Gefitinib Methotrexate Mitomycin Paclitaxel Vinca alkaloids + mitomycin Roig J et al. Clin Pulm Med 2006; Inoue A. Lancet 2003
- 9. Chemotherapeutic agents used in lung cancer that may cause pulmonary fibrosis Cyclophosphamide Etoposide Methotrexate Mitomycin Nitrosureas Roig J et al. Clin Pulm Med 2006
- 10. Chemotherapeutic agents used in lung cancer that may cause pleural disease Cyclophosphamide Docetaxela Doxorubicinb Methotrexate Mitomycin Procarbazine Vinblastine + mitomycin Roig J et al. Clin Pulm Med 2006 a Trasudative pleural effussion caused by fluid retention syndrome b Trasudative pleural effussion caused by congestive heart failure
- 11. Chemotherapeutic agents used in lung cancer that may cause an hypersensitivity reaction with respiratory symptoms Roig J et al. Clin Pulm Med 2006 Docetaxel Etoposide Gemcitabine Ifosfamide + mesna Irinotecan Methotrexate Mitomycin Paclitaxel Procarbazine Topotecan Vinca alkaloids
- 12. Bronchial artery infusion in central lung cancer and metastasis Risk of massive hemoptysis 1 to 3 months after BAI Herald: hemoptoic sputum Need urgent arteriography Bronchial vascular fistula Rare esophageal ulceration Bronchial esophageal fistula Spinal cord damage Osaki T. Chest 1999; Suzuki T. J Bronchol 2001
- 13. Neglected respiratory toxicity(1) • Vincristine, procarbazine, cytarabine, chlorambucil may cause neuropathy that might affect respiratory muscle function • Does it imply an increased anesthesia risk ? • Risk of acute encephalopaty and respiratory depression with ifosfamide, metothrexate in SAS and advanced COPD with hypercapnic failure Aldrich T, Clin Chest Med 1990; Klein D, Can A Sc J 1983; Roig J, Clin Pulm Med 2006
- 14. Neglected respiratory toxicity(2) • Some cases of intrathoracic extravasation • Venous thromboembolism associated with central venous lines and subcutaneous ports • Increased hypercoagulability of concomitant therapies (erythropoietin, megestrol acetate) and malignancy itself Bozkurt AK.. Am J Clin Oncol 2003; Verso M. J Clin Oncol 2003; Biffi R. Cancer 2001; Bauer K. J Clin Oncol 2000; Wun T. Cancer 2003, Bolen J. A Am Med Dir Assoc 2000
- 15. Chemoterapy-induced lung toxicity: prevention in COPD • High-risk (30%) if nitrosureas are used • Sleepness with ifosfamide, methotrexate • More risk in “overlap”: COPD + SAS • Water retention: taxotere, ciclophosphamide • Increased risk of O2 toxicity • Sensorimotor neuropathy and interactions
- 16. Ifosfamide-induced lung toxicity Clinical presentation Respiratory features Incidence Outcome Acute Hypersensitivity reaction (mesna) Encephalopathy and respiratory depressiona Rare acute pneum CNS depression <12% Usually recovery a Concern in advanced COPD and SAS Cameron JC. Cancer Nurs 1993; Baker WJ. Cancer 1990
- 17. Campothecin-induced lung toxicity Agent Type Incidence Outcome Topotecan Irinotecan (CPT-11) Mild dyspnea Dyspnea Acute pneumonitis <3% < 22% 1-13% Reversible Maksymiuk A, Am J Clin Oncol 1998; Masuda N, J Clin Oncol 1992;Takeda K, Br J Cancer 1999
- 18. Gemcitabine-induced lung toxicity Clinical presentation Respiratory features Incidence Outcome Acute Hypersensitivity reaction Acute pneumonitis Rarely ARDS, PVODa <1 % Usually complete recovery except in ARDS a Pulmonary venoocclusive disease Proc ASCO 2000; Tempero MA. Cancer 1998; Marruchella A. Eur Resp J 1998; Nackaerts KL. Ann Oncol 1998; Vansteenkiste J. Lung Cancer 2001.
- 19. Mitomycine - induced lung toxicity Clinical presentation Respiratory features Incidence Outcome Acute Chronic, dose-related (total dose >30 mg/m2 ) Acute pneumonitis Very rarely thrombotic microangiopathy with ARDS 3 % -12 % Fatality rate 40% Increased risk if combined therapy with vinca alk. Increased risk of microangiopathy if associated with fluoruracil (highest mortality) Rivera MP. Am J Clin Oncol 1995, Linette DC. Ann Pharm 1992, Verweij J. Cancer 1987 Thompson C. South Med J 1992 A
- 20. Paclitaxel - induced lung toxicity Clinical presentation Respiratory features Incidence Outcome Acute Hypersensitivity reaction Acute pneum. HR <1% if pretreated Rare if dosage <350mg/m2 Usually recovery with mandatory pretreatment Risk of ARDS if high dose therapy or concomitant radiotherapy Essayan DM. J Clin Oncol 1996; Bookman MA. Ann Oncol 1997 Ramanthan R. Chest 1996; Robert F. Semin Radiat Oncol 1999
- 21. Docetaxel - induced lung toxicity Clinical presentation Respiratory features Incidence Outcome Acute Chronic Acute pneumonitis Fluid retention syndrome Very rare Increased risk of retention if >400 mg/m2 Usually complete recovery Etienne B. Rev Mal Respir 1998; Briasoulis E. Respiration 2000
- 22. DIFF. DIAGNOSIS: ALGORITHMIC APPROACH Chest symptoms + abnormal X-ray Clinical evaluation Non-infectious cause Infection not excluded Appropriate treatment Non-invasive work-up Early antibiotic No impr. Improved Continue AbInvasive proc.Keep Ab + -
- 23. Invasive diagnostic work-up •FOB: bronchial aspirates, PSB, BAL, TBB •Transthoracic needle aspiration (TNA) •Lung biopsy – VATS •Open lung biopsy: minithoracotomy Dorca J. 1995: ultrathin (25G)TNA in 97 cases of non-mechanically ventilated pneumonia Transient hemoptysis: 5 cases (5.2%) Self-limited partial pneumothorax: 3 cases (3%) Sensitivity 60.9%; PPV 100%; modified treatment in 30%
- 24. HRCT in patients with dyspnea, fever of unknown origin and normal X-ray • Immunocompromise, severe emphysema • May detect an unsuspected alveolar infiltrate or a subtle interstitial pattern • Guide for FOB techniques ► better yield Brown MJ. Acute lung disease in the immunocpmpromised host: CT and pathologic findings. Radiology 1994; Ramila E. Bronchoscopy guided by HRCT for the diagnosis of pulmonary infections in patients with hemathologic malignancies and normal plain chest X-rays. Haematologica 2000
- 25. Reliability of transbronchial biopsy • High utility only in case of: –Sarcoidosis –Lung cancer and some mestastases –Opportunistic infections in immunocompromised host –Lung transplantation Gal A. Adv Anat Pathol 2005
- 26. Lymphatic carcinomatosis may mimic severe bronchial asthma • Mendeloff A. Severe asthmatic dyspnea as the sole presenting symptom of generalized endolymphatic carcinomatosis: report of two cases with autopsy findings and review of the literature. N Eng J Med 1945 • Masson RG. Pulmonary microvascular cytology in the diagnosis of lymphangitic carcinomatosis. N Eng J Med 1989
- 27. Microscopic pulmonary tumor embolism may cause respiratory failure • Sometimes is the initial, subacute presentation of occult malignancy • Clue: precapillary pulmonary hypertension without thromboembolic disease and negative usual complementary tests • Value of wedge aspiration cytology Masson RG. Pulmonary microvascular cytology. A new diagnostic application of the pulmonary artery catheter. Chest 1985; Stucky A. A rare cause of fatal right heart failure. Eur J Intern Med 2006
- 28. Chemoterapy-induced lung toxicity: therapeutic approach • Early detected, non-severe cases: cessation • Severe cases: steroids on a timely fashion • Dosage & tapering: individualized basis • Transplant? (Santamauro JT, Chest 1994) • Desensitization possible, not recommended • Premedication mandatory with some agents • Future: Gene therapy? (West J, Chest 2001)