Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Targeted Oncology
Published in: Targeted Oncology 4/2011

01-12-2011 | Review

Pulmonary toxicities from targeted therapies: a review

Authors: Nicholas A. Barber, Apar Kishor Ganti

Published in: Targeted Oncology | Issue 4/2011

Login to get access

Abstract

Pulmonary toxicity is rarely seen with most commonly used targeted therapies. The endothelial growth factor receptor (EGFR) small-molecule tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib can cause interstitial lung disease (ILD). BCR-ABL tyrosine kinase inhibitors imatinib and dasatinib can cause pleural effusions. Infusion-related bronchospasm is common with the monoclonal antibodies to EGFR cetuximab and panitumumab, and case reports of bronchiolitis and pulmonary fibrosis have been described. Up to one-sixth of patients taking mammalian target of rapamycin (mTOR) inhibitors get a reversible interstitial pneumonitis. Bevacizumab, the monoclonal antibody to vascular endothelial growth factor (VEGF), has been associated with hemoptysis and pulmonary embolism particularly in patients with squamous cell lung cancer. Infusion-related bronchospasms, acute respiratory distress syndrome (ARDS), and interstitial pneumonitis can be seen with the anti-lymphocyte monoclonal antibodies rituximab, ofatumumab, and alemtuzumab. While most pulmonary toxicities from these therapies are mild and resolve promptly with dose reduction or discontinuation, it is important for the clinician to recognize these potential toxicities when faced with treatment-related complications. Discerning these pulmonary adverse effects may help in making decisions on diagnostic testing and therapy, particularly for those with pulmonary and cardiovascular co-morbidities.
Literature
1.
Cohen MH, Williams GA et al (2003) FDA drug approval summary: gefitinib (ZD 1839) (Iressa®) tablets. Oncologist 8:303–306PubMedCrossRef
2.
Cohen MH et al (2005) FDA drug approval summary: erlotinib (Tarceva®) tablets. Oncologist 10:461–466PubMedCrossRef
3.
O’Brien SG et al (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348:994–1004PubMedCrossRef
4.
Druker BJ et al (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355:2408–2417PubMedCrossRef
5.
Kantarjian H et al (2010) Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 362:2260–2270PubMedCrossRef
6.
Saglio G et al (2010) Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 362:2251–2259PubMedCrossRef
7.
Cutsem EV et al (2009) Cetuximab and chemotherapy as initial treatment for colorectal cancer. N Eng J Med 360:1408–1417CrossRef
8.
Cutsem EV et al (2007) Open-labeled phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25:1658–1664PubMedCrossRef
9.
Motzer R et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456PubMedCrossRef
10.
Motzer R et al (2010) Phase III trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 116:4256–4265PubMedCrossRef
11.
Fukuoka M, Yano S et al (2003) Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 21:2237–2246PubMedCrossRef
12.
Kris MG, Natale RB et al (2003) Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer. JAMA 290:2149–2158PubMedCrossRef
13.
Mok TS, Wu YL et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947–957PubMedCrossRef
14.
Maemondo M, Inoue A et al (2010) Gefitinib or chemotherapy for non-small cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388PubMedCrossRef
15.
Cohen MH et al (2003) FDA drug approval summary: gefitinib (ZD1839) (Iressa®) tablets. Oncologist 8:303–306PubMedCrossRef
16.
Ando M, Okamoto I et al (2006) Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol 24:2549–2556PubMedCrossRef
17.
Paez JG et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500PubMedCrossRef
18.
19.
Dimopoulou I et al (2006) Pulmonary toxicity from novel antineoplastic agents. Ann Onc 17:372–379CrossRef
20.
Danson S et al (2005) Interstitial lung disease in lung cancer: separating disease progression from treatment effects. Drug Saf 28:103–113PubMedCrossRef
21.
Suzuki M et al (2008) Recurrent gefitinib-induced interstitial lung disease. Intern Med 47:533–536PubMedCrossRef
22.
Herbst RS et al (2005) TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 23:5892–5899PubMedCrossRef
23.
Gatzemeier U et al (2007) Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the tarceva lung cancer investigation trial. J Clin Oncol 25:1545–1552PubMedCrossRef
24.
Moore MJ et al (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the national cancer institute of Canada clinical trials group. J Clin Oncol 25:1960–1966PubMedCrossRef
25.
26.
Makris D et al (2007) Fatal interstitial lung disease associated with oral erlotinib therapy for lung cancer. BMC Cancer 7:150PubMedCrossRef
27.
Geyer CE et al (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355:2733–2743PubMedCrossRef
28.
Bokemeyer C et al (2008) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27:663–671PubMedCrossRef
29.
Vermorken JB et al (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Eng J Med 359:1116–1127CrossRef
30.
Lenz HJ (2007) Management and preparedness for infusion and hypersensitivity reactions. Oncologist 12:601–609PubMedCrossRef
31.
32.
Giusti RM et al (2008) U.S. Food and drug administration approval: panitumumab for epidermal growth factor receptor—expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Clin Cancer Res 14:1296–1302PubMedCrossRef
33.
Slamon DJ et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpress HER2. N Engl J Med 344:783–792PubMedCrossRef
34.
Romond EH et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684PubMedCrossRef
35.
DeMatteo RP et al (2009) Placebo-controlled randomized trial of adjuvant imatinib mesylate following the resection of localized, primary gastrointestinal stromal tumor (GIST). Lancet 373:1097–1104PubMedCrossRef
36.
Demetri GD et al (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347:472–480PubMedCrossRef
37.
Quintás-Cardama A et al (2007) Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure. J Clin Oncol 25:3908–3914PubMedCrossRef
38.
Kantarjian H et al (2007) Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood 109:5143–5150PubMedCrossRef
39.
Stephens J et al (2010) The burden of managing pleural effusions in patients with chronic myelogenous leukemia post-imatinib failure: a literature-based economic analysis. Int J Gen Med 3:31–36PubMed
40.
Rajda J, Phatak PD (2005) Reversible drug-induced interstitial pneumonitis following imatinib mesylate therapy. Amer J Hem 79:80–81CrossRef
41.
Yamasawa H et al (2008) Drug-induced pneumonitis associated with imatinib mesylate in a patient with idiopathic pulmonary fibrosis. Respiration 75:350–354PubMedCrossRef
42.
43.
Bergeron A et al (2007) Lung abnormalities after dasatinib treatment for chronic myeloid leukemia: a case series. Am J Res Crit Care Med 176:814–818CrossRef
44.
Kaelin W (2004) The von hippel-lindau tumor suppressor gene and kidney cancer. Clin Cancer Res 10:6290S–6295SPubMedCrossRef
45.
Pham P et al (2004) Sirolimus-associated pulmonary toxicity. Clin Transplant 77:1215–1220
46.
Miwa Y et al (2008) Tacrolimus-induced lung injury in a rheumatoid arthritis patient with interstitial pneumonitis. Mod Rheumat 18:208–211CrossRef
47.
48.
White D et al (2010) Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Res Crit Care Med 182:396–403CrossRef
49.
Porta C, et al. (2009) Recommendations for adverse event management in patients with renal cell carcinoma treated with everolimus: safety data from the RECORD-1 Trial: Poster Presented at the 8th International Kidney Cancer Symposium, Chicago, IL, September 25–26, 2009
50.
Hudes G et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Eng J Med 356:2271–2281CrossRef
51.
Bellmunt J et al (2008) Temsirolimus safety profile and management of toxic effects in patients with advanced renal cell carcinoma and poor prognostic features. Ann Onc 19:1387–1392CrossRef
52.
53.
Duran I et al (2006) Characterisation of the lung toxicity of the cell cycle inhibitor temsirolimus. Euro J Cancer 42:1875–1880CrossRef
54.
Hurwitz H et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Eng J Med 350:2335–2342CrossRef
55.
Sandler A et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for Non-small-cell lung cancer. N Eng J Med 355:2542–2550CrossRef
56.
Rini B et al (2008) Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Onc 26:5422–5428CrossRef
57.
Johnson D et al (2004) Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Onc 22:2184–2191CrossRef
58.
Myung HJ et al (2010) Sorafenib-induced interstitial pneumonitis in a patient with hepatocellular carcinoma: a case report. Gut and Liver 4:543–546PubMedCrossRef
59.
Seidel C et al (2010) Recall pneumonitis during systemic treatment with sunitinib. Ann Oncol 21(10):2119–2120PubMedCrossRef
60.
Leon RJ et al (1994) Rituximab-induced acute pulmonary fibrosis: letters to the editor. Mayo Clin Proc 79:949–950CrossRef
61.
Burton C et al (2003) Interstitial pneumonitis related to rituximab therapy: to the editor. N Eng J Med 348:2690–2691CrossRef
62.
Kim KM et al (2008) Rituximab-CHOP induced interstitial pneumonitis in patients with disseminated extranodal marginal zone B cell lymphoma. Yonsei Med J 49:155–158PubMedCrossRef
63.
Herishanu Y et al (2006) Fatal interstitial pneumonitis related to rituximab-containing regimen. Clin Lymphoma Myeloma 6:407–409PubMedCrossRef
64.
Lim KH et al (2010) Severe pulmonary adverse effects in lymphoma patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen plus rituximab. Korean J Intern Med 25:86–92PubMedCrossRef
65.
Swords R et al (2004) Interstitial pneumonitis following rituximab therapy for immune thrombocytopenic purpura (ITP). Amer J Hem 77:103–104CrossRef
66.
Kishi J et al (2009) A case of rituximab-induced interstitial pneumonitis observed in systemic lupus erythematosus. Rheumatology 48:447–448PubMedCrossRef
67.
Lioté H et al (2010) Rituximab-induced lung disease: a systematic literature review. Eur Respir J 35:681–687PubMedCrossRef
68.
Ofatumumab CBD (2010) A novel anti-CD20 monoclonal antibody for the treatement of B-cell malignancies. J Clin Oncol 28:1–6CrossRef
69.
Osterborg A et al (2008) Ofatumumab (HuMax-CD20), a novel CD20 monoclonal antibody, is an active treatment for patients with CLL refractory to both fludarabine and alemtuzumab or bulky fludarabine-refractory disease: results from the planned interim analysis of an international pivotal trial. Blood 112:126–127
70.
Coiffier B et al (2008) Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1–2 study. Blood 111:1094–1100PubMedCrossRef
71.
Keating MJ et al (2002) Therapeutic role of alemtuzumab (campath-1H) in patients who have failed fludarabine: results of a large international study. Blood 99:3554–3561PubMedCrossRef
72.
Lozanski G et al (2004) Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletions. Blood 103:3278–3281PubMedCrossRef
73.
Sachdeva A, Matuschak GM (2008) Diffuse alveolar hemorrhage following alemtuzumab. Chest 133:1476–1478PubMedCrossRef
74.
San Miguel JF et al (2008) Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 359:906–917PubMedCrossRef
75.
Goy A, et al. (2006) Bortezomib in relapsed or refractory mantle cell lymphoma (MCL): Results of the PINNACLE study. J Clin Oncol. 2006 ASCO Annual Meeting Proceedings PartI. Vol 24, No. 18S (June 20 Supplement):7512
76.
Miyakoshi S et al (2006) Severe pulmonary complications in Japanese patients after bortezomib treatment for refractory multiple myeloma. Blood 107:3492–3494PubMedCrossRef
77.
Zappasodi P et al (2007) Rapid response to high-dose steroids of severe bortezomib-related pulmonary complications in multiple myeloma. J Clin Oncol 25:3380–3381PubMedCrossRef
78.
Rajkumar SV et al (2005) Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the eastern cooperative group. J Clin Oncol 24:431–436PubMedCrossRef
79.
Rajkumar SC et al (2005) Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 106:4050–4053PubMedCrossRef
80.
List A et al (2006) Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 355:1456–1465PubMedCrossRef
81.
Bennett CL et al (2006) Thalidomide and lenalidomide-associated thromboembolism among patients with cancer. JAMA 296:2558–2560PubMedCrossRef
82.
Onozawa M, et al. (2005) Thalidomide-induced interstitial pneumonitis. J Clin Oncol 2425–2426
83.
Sasaki M et al (2008) Thalidomide may induce interstitial pneumonia preferentially in Japanese patients. Euro J Haem 82:73–74CrossRef
84.
Feaver AA et al (2006) Thalidomide-induced organizing pneumonia. So Med J 99:1292–1294CrossRef
85.
Tilluckdharry L et al (2008) Thalidomide-related eosinophilic pneumonia: a case report and brief literature review. Cases Journal 1:1–4CrossRef
86.
Chen C et al (2009) Expanded safety experience with lenalidomide plus dexamethasone in relapsed or refractory multiple myeloma. Brit J Haemat 146:164–170PubMedCrossRef
Metadata
Title
Pulmonary toxicities from targeted therapies: a review
Authors
Nicholas A. Barber
Apar Kishor Ganti
Publication date
01-12-2011
Publisher
Springer-Verlag
Published in
Targeted Oncology / Issue 4/2011
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-011-0199-0

Other articles of this Issue 4/2011

Targeted Oncology 4/2011 Go to the issue

Review

Hypomagnesaemia and targeted anti-epidermal growth factor receptor (EGFR) agents

Editorial

The carriages to the good drivers

Review

Heart to heart with trastuzumab: a review on cardiac toxicity

Day-to-Day Practice

Posterior reversible encephalopathy syndrome induced by anti-VEGF agents

Review

Cardiovascular toxicity of anti-angiogenic drugs

Review

Tyrosine kinase inhibitor-induced hypothyroidism: incidence, etiology, and management
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits