scholarly journals Successful Rechallenge with Osimertinib after Very Acute Onset of Drug-Induced Pneumonitis

2021 ◽  
pp. 733-738
Author(s):  
Turab Mohammed ◽  
Shaunak Mangeshkar ◽  
Joerg Rathmann
Keyword(s):  
Kinase Inhibitor ◽  
Clinical Symptoms ◽  
Radiological Finding ◽  
Growth Factor Receptor ◽  
Pulmonary Involvement ◽  
Acute Onset ◽  
Treatment Withdrawal ◽  
High Dose ◽  
Drug Induced ◽  
Radiographic Findings

Drug-induced interstitial lung disease (DI-ILD) is a rare, yet life-threatening complication associated with tyrosine-kinase inhibitor (TKI) therapy. Third-generation epidermal growth factor receptor-TKI, osimertinib use can be associated with a benign radiological finding called transient asymptomatic pulmonary opacities that can be confused with an infectious pulmonary process resulting in overtreatment with antibiotics or premature treatment withdrawal or severe DI-ILD. In this case, our patient with newly diagnosed metastatic non-small cell lung cancer on treatment with osimertinib developed very early onset severe DI-ILD (grade-IV) with a unique pattern of pulmonary involvement and was treated with high-dose corticosteroids with a response. She was later successfully rechallenged with osimertinib and responded well to the treatment. Our case highlights the importance of being cognizant of the possibility that DI-ILD can rarely occur within a week of treatment initiation with osimertinib and safe reintroduction of the drug is possible in select patients following complete resolution of pulmonary radiographic findings and clinical symptoms even with high-grade adverse events.

scholarly journals Recent updates on the management of autoimmune hepatitis

2021 ◽  
Vol 27 (1) ◽  
pp. 58-69
Author(s):  
Atsumasa Komori
Keyword(s):  
Autoimmune Hepatitis ◽  
Clinical Manifestations ◽  
Serum Biochemistry ◽  
Acute Onset ◽  
Relative Increase ◽  
Treatment Withdrawal ◽  
First Line ◽  
Drug Induced ◽  
Smooth Muscle Antibody ◽  
First Line Therapy

Autoimmune hepatitis (AIH) is an immunoinflammatory chronic liver disease with dynamic and rather heterogeneous disease manifestations. A trend of increasing prevalence of AIH has been observed worldwide, along with a relative increase in the percentage of male patients. AIH is characterized and diagnosed based on serum biochemistry and liver histology: elevated aminotransferases and serum immunoglobulin G (IgG), the presence of serum anti-nuclear antibody or anti-smooth muscle antibody, and interface lympho-plasmacytic hepatitis. Clinical manifestations differ among disease subtypes with distinct time-frames, i.e., AIH with a chronic insidious onset, and acute-onset AIH (the diagnosis of which is often challenging due to the lack of typical serum findings). The absence of disease-specific biomarkers or histological findings may expand the disease phenotype into drug-induced AIH-like liver injury. Corticosteroids and azathioprine are recommended first-line treatments for AIH. The complete normalization of aminotransferases and serum IgG is an essential treatment response to ensure long-term overall survival. An incomplete response or intolerance to these drugs is considered an indication for second-line treatment, especially with mycophenolate mofetil. Life-long maintenance treatment is required for the majority of patients, but the few who achieve prolonged and stringent biochemical remission with lower alanine aminotransferase and IgG within the normal range may be able to discontinue the medications. In the future, the quality of life of AIH patients should be managed by personalized medicine, including the appropriate selection and dosing of first-line therapy and perhaps alternating with potential therapeutics, and the prediction of the success of treatment withdrawal.

Severe cutaneous presentation of hydralazine-induced ANCA vasculitis without renal or pulmonary involvement, complicated by DIC

2021 ◽  
Vol 14 (5) ◽  
pp. e238609
Author(s):  
Mae Xintong Huo ◽  
Alzira Rocheteau M Avelino ◽  
Gurpreet Singh
Keyword(s):  
Intensive Therapy ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Pulmonary Involvement ◽  
High Dose ◽  
Diagnostic Challenge ◽  
Drug Induced ◽  
Mucosal Involvement ◽  
Ulcerative Lesions ◽  
Long Term Prognosis

Hydralazine is a common arterial vasodilator used in the management of congestive heart failure and hypertension. It can be associated with drug-induced lupus and less commonly antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). Drug-induced AAV typically has a favourable long-term prognosis. It is not commonly associated with primary skin involvement, as most cases also have notable kidney and lung disease. Cases with isolated skin findings are rare. We present a rare case of a 60-year-old woman on long-term hydralazine who presented with AAV with primary skin and mucosal involvement, in the form of diffuse bullous and ulcerative lesions, which posed a diagnostic challenge. Her hospital course was marked by several complications including disseminated intravascular coagulation. She required intensive therapy with high-dose steroids, plasmapheresis and rituximab. She tolerated immunosuppression well and with multidisciplinary supportive care, she recovered well and was able to be discharged from the hospital.

scholarly journals Diagnosis and treatment of drug-induced interstitial lung disease

2021 ◽  
Vol 64 (4) ◽  
pp. 286-295
Author(s):  
Sanghoon Park ◽  
Eun Joo Lee
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Clinical Symptoms ◽  
Checkpoint Inhibitors ◽  
Interstitial Fibrosis ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Drug Induced ◽  
Fibrotic Process ◽  
Epidermal Growth

Drug-induced interstitial lung disease (DILD) is a group of adverse drug reactions that is rare but fatally toxic. Pulmonary toxicity causes inflammation and subsequent interstitial fibrosis. As novel drugs with a variety of purposes are introduced into the medical field, the number of culprit medications that are suspected to cause lung complications is accordingly increasing. In this review, DILD will be discussed from several aspects such as causality by numerous drugs, check points for a timely diagnosis, alongside some contemporary treatment options. The exact mechanism of DILD has not been elucidated, and a useful clinical, radiological, or pathological confirmation process is still lacking. Common drugs which casue DILD include bleomycin, amiodarone, epidermal growth factor receptor-targeted agents, and immune checkpoint inhibitors. Diagnosis is based on a suspicious drug administration history, somewhat inconsistent clinical symptoms and signs, radiological hints, and histopathological assistance, together with the exclusion of other lung-injuring etiologies. Cessation of the suspected drug, meticulous corticosteroid usage, and ancillary supportive management are the mainstay therapeutic strategy for DILD. Most cases of DILD respond to these countermeasures and reductions, but in some cases the fibrotic process worsens, leading to irreversible sequelae on the affected lung.

scholarly journals Severe polymyositis occurring in a cancer patient directly after chemotherapy: etiology and management

2021 ◽  
pp. FSO706
Author(s):  
Charles Soutif ◽  
Thaïs Tison ◽  
Isabelle Focant ◽  
Emmanuel Seront
Keyword(s):  
Colorectal Cancer ◽  
Muscle Weakness ◽  
Immune Modulation ◽  
Intravenous Immunoglobulins ◽  
Acute Onset ◽  
High Dose ◽  
Drug Induced ◽  
Muscle Enzyme ◽  
High Dose Methylprednisolone ◽  
Colorectal Cancer Patients

A 72-year-old woman was diagnosed with metastatic colorectal cancer and treated with oxaliplatin-based chemotherapy and bevacizumab. One week after the second administration of chemotherapy, she presented acute-onset dysphagia and rapidly progressing proximal muscle weakness, associated with elevation of the creatinine phosphokinase enzymes. Magnetic resonance imaging raised suspicion of polymyositis. Etiology remained unclear but paraneoplastic origin or immune modulation by chemotherapy was considered. High-dose methylprednisolone and intravenous immunoglobulins were started with continuation of chemotherapy. Although there was rapid normalization of muscle enzyme, the general status deteriorated rapidly with aggravation of dysphagia, complete immobilization and death. This case highlights the importance of considering muscle weakness as paraneoplastic syndrome or drug-induced toxicity in colorectal cancer patients. Despite aggressive management, prognosis remains poor.

A phase II study of mammalian target of rapamycin (mTOR) inhibitor RAD001 plus imatinib mesylate (IM) in patients with previously treated advanced renal carcinoma (RCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15600-15600 ◽  
Author(s):  
J. S. Chan ◽  
J. Vuky ◽  
L. A. Besaw ◽  
T. M. Beer ◽  
C. W. Ryan
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Performance Status ◽  
Growth Factor Receptor ◽  
High Dose ◽  
Grade 3 ◽  
Asco 2006 ◽  
Free Rate

15600 Background: The serine-threonine kinase mTOR is a valid target for RCC therapy with temsirolimus treatment resulting in improved overall survival in poor-risk patients (Hudes G et al., ASCO 2006). RAD001 is an oral inhibitor of mTOR which has demonstrated activity in RCC at 10mg/day (Amato R et al., ASCO 2006). IM is a tyrosine kinase inhibitor (TKI) of platelet-derived growth factor receptor (PDGFR), a target that may promote angiogenesis and growth of RCC. Combined mTOR and PDGFR inhibition with RAD001 and IM may achieve vertical blockade through the PI3K/AKT pathway. Methods: Eligibility: metastatic clear cell RCC, performance status (PS) 0–2, adequate organ function, and prior treatment with = 1 systemic therapy. Doses were based on a phase I study of the combination in GIST (Van Oosterom AT et al., ASCO 2005): RAD001 2.5 mg p.o. daily and IM 600 mg p.o. daily. Patients were reimaged every 6 weeks. This is a 2-stage phase II study to determine the 3-month progression-free rate. Results: 14 pts have been enrolled. Median age 66 years (51–79). 6 pts PS 0 and 8 pts PS 1. Median number of prior therapies 1.5 (1–4). 12 of 14 patients had prior TKI therapy. Prior therapies included sorafenib (11 pts), interferon (7), sunitinib (3), bevacizumab (2), erlotinib (1), panitumumab (1), high-dose IL-2 (1). Of 10 pts evaluable for the primary endpoint, 3 are progression-free = 3 months. Best response for 9 pts evaluable by RECIST: PR/CR 0, SD 7, PD 2. Most common adverse events in 11 evaluable patients include nausea (8), edema (7), increased creatinine (7), fatigue (7), transaminase elevation (6), thrombocytopenia (5), leukopenia (5), cough (5), diarrhea (5). Grade 3 adverse events include fatigue (3), LE edema, rash, pleural effusion, increased creatinine, abdominal pain, and thrombocytopenia (1 each). There were no grade 4 toxicities. Unique suspected RAD001 toxicities include grade 3 pneumonitis (1) and angioedema (1). Conclusions: The combination of RAD001 and IM has moderate toxicity. This is one of the first studies in RCC patients predominantly pretreated with a TKI. 3 month progression-free rate appears to be a clinically relevant endpoint in this population. [Table: see text]

scholarly journals Oral ulcers in patients treated with palbociclib: a case report

2018 ◽  
Vol 24 (2) ◽  
pp. 60-62
Author(s):  
Cédric Alande ◽  
Mathilde Fénélon ◽  
Jean-Christophe Fricain
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Pulmonary Involvement ◽  
Infrared Laser ◽  
Drug Induced ◽  
Oral Ulcers ◽  
First Case ◽  
Aphthous Ulcers ◽  
Breast Cancer Relapse ◽  
Er Positive

Introduction: Palbociclib is an approved drug in the treatment of women with advanced or metastatic estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, breast cancer. The purpose of this article is to present the first case ever described of oral ulcers caused by palbociclib. Observation: A case of drug-induced oral ulcers is reported. The patient was treated with a combination of palbociclib and Fulvestrant for a breast cancer relapse with pulmonary involvement. These ulcers were localized on the ventral face of the tongue and on the gum. A therapeutic combination of infrared laser biostimulation and a topical application of Dermoval® and Dynexan® were carried out. Palbociclib was concurrently discontinued. The lesions healed in about 15 days. Comments: Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 (CDK 4/6). Thereby, it blocks many signaling pathways responsible for cell proliferation. This property weakens the oral mucosa and could be the cause of the observed ulcers. These latter having been particularly debilitating for the patient. Conclusion: Palbociclib-related oral aphthous ulcers are similar to those reported with other targeted therapies. The combination of infrared laser biostimulation and local corticosteroid therapy did not prevent the discontinuation of the cancer treatment.

scholarly journals Osimertinib rechallenge under steroid protection following osimertinib-induced pneumonitis: three case studies

2021 ◽  
Vol 13 ◽  
pp. 175883592110180
Author(s):  
Christiane Bickert ◽  
Kathrin Kahnert ◽  
Diego Kauffmann-Guerrero ◽  
Jeremias Götschke ◽  
Zulfiya Syunyaeva ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Treatment Options ◽  
Case Series ◽  
Growth Factor Receptor ◽  
Small Cell Lung ◽  
First Line ◽  
Drug Induced ◽  
Discontinuation Of Treatment ◽  
Epidermal Growth ◽  
Treatment Switch

Osimertinib is a third-generation tyrosine kinase inhibitor that became the preferred first-line treatment option for metastatic non-small cell lung cancer with sensitizing epidermal growth factor receptor mutations. Drug-induced pneumonitis is known to occur with osimertinib. In case of severe pneumonitis, discontinuation of treatment and therapy with corticosteroids is recommended, and a treatment switch is usually performed. We herein report the treatment course in three patients who were rechallenged with osimertinib under steroid protection following an osimertinib-induced pneumonitis. All our patients were initially re-exposed to a lower dose of osimertinib. Two patients were successfully rechallenged under prednisolone protection. The third patient, who was initially retreated with osimertinib without steroid protection, suffered from a recurrent pneumonitis, and was later rechallenged successfully under steroid protection. Our case series indicates that rechallenge with osimertinib following recovery from osimertinib-induced pneumonitis allows a successful rechallenge in individual cases when alternative treatment options are lacking. Concomitant steroids appear to protect against flares of pneumonitis during rechallenge.

Case Example: Adjacent Segment Disease: What Is It, and How Is It Rated?

2011 ◽  
Vol 16 (2) ◽  
pp. 8-9
Author(s):  
Marjorie Eskay-Auerbach
Keyword(s):  
Clinical Symptoms ◽  
Lumbar Fusion ◽  
Adjacent Segment Degeneration ◽  
Adjacent Segment Disease ◽  
Adjacent Segment ◽  
Disc Space Narrowing ◽  
Disc Disease ◽  
Disc Space ◽  
Radiographic Findings ◽  
Asymptomatic Patients

Abstract The incidence of cervical and lumbar fusion surgery has increased in the past twenty years, and during follow-up some of these patients develop changes at the adjacent segment. Recognizing that adjacent segment degeneration and disease may occur in the future does not alter the rating for a cervical or lumbar fusion at the time the patient's condition is determined to be at maximum medical improvement (MMI). The term adjacent segment degeneration refers to the presence of radiographic findings of degenerative disc disease, including disc space narrowing, instability, and so on at the motion segment above or below a cervical or lumbar fusion. Adjacent segment disease refers to the development of new clinical symptoms that correspond to these changes on imaging. The biomechanics of adjacent segment degeneration have been studied, and, although the exact mechanism is uncertain, genetics may play a role. Findings associated with adjacent segment degeneration include degeneration of the facet joints with hypertrophy and thickening of the ligamentum flavum, disc space collapse, and translation—but the clinical significance of these radiographic degenerative changes remains unclear, particularly in light of the known presence of abnormal findings in asymptomatic patients. Evaluators should not rate an individual in anticipation of the development of changes at the level above a fusion, although such a development is a recognized possibility.

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