ABSTRACT
BACKGROUND: Targeted therapies are a standard of care for first-line treatment of Anaplastic lymphoma kinase (ALK)-rearranged non small cell lung cancer (NSCLC). Giving the rapid pace of drug discovery and development in this area, reporting of adverse effects of ALK inhibitors is crucial. Here, we report a case of osteitis induced by an ALK inhibitor mimicking bone metastasis, a previously undescribed side effect of crizotinib. CASE PRESENTATION: A 31-year-old woman with stage IV ALK-rearranged NSCLC presented with back pain after 3 months of crizotinib treatment. Diagnostic work-up showed osteitis on the 4th and 5th thoracic vertebrae, anterior soft tissue infiltration and epiduritis, without any sign of infection. Spinal cord decompression, histological removal and osteosynthesis were performed. Histologic examination showed necrosis with abundant peripheral neutrophils, no microorganism nor malignant cell. Symptoms and Computarized Tomography-abnormalities rapidly diseappeared after crizotinib withdrawal and did not recur after ceritinib onset. CONCLUSIONS: This is the first report of crizotinib-induced osteitis. Crizotinib differs from other ALK inhibitors as it targets other kinases as well, which may have been responsible for the osteitis. Crizotinib can induce rapidly extensive osteitis, which can mimic tumor progression.
Subject(s)
Anaplastic Lymphoma Kinase/antagonists & inhibitors , Antineoplastic Agents/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Crizotinib/adverse effects , Lung Neoplasms/drug therapy , Osteitis/chemically induced , Protein Kinase Inhibitors/adverse effects , Adult , Anaplastic Lymphoma Kinase/genetics , Antineoplastic Agents/therapeutic use , Bone Neoplasms/diagnosis , Bone Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Crizotinib/therapeutic use , Female , Humans , Lung Neoplasms/complications , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Osteitis/diagnostic imaging , Osteitis/pathology , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Sulfones/pharmacology , Tomography, X-Ray ComputedABSTRACT
The treatment of rheumatoid arthritis (RA) was revolutionized by the introduction of the biologics. Their power and their good safety profile have allowed to define new objectives and procedures to reach them; it is the "treat to target" concept. New recommendations were published by EULAR or ACR to obtain the remission as soon as possible. Disease-modifying antirheumatic drugs, in particular the methotrexate (MTX), remain the cornerstone of RA treatment in association with symptomatic treatments. The use of corticosteroids can be necessary to control the disease activity in the waiting time of the DMARDs efficiency or to control a flare. The absence of remission after 3months after initiation of MTX should prompt the rheumatologist to intensify the treatment with biologics. The increasing number of biologics targeting different mechanisms (5 anti-tumor necrosis factor-α, antagonist of interleukine-1 [IL-1] receptor, antagonist of IL-6 receptor, anti-CD20, anti-cytotoxic T-lymphocyte antigen 4) asks the question of the strategy in their prescription. Besides, all the registers or meta-analysis plead in favor of a good safety subject to a moderate prescription and to a greater vigilance. Except the opportunist infections, it is more the comorbidities or the associated treatments such as corticoids or MTX, which would favor the infections than anti-TNFα. There is no indication that biologics may increase the risk of solid cancer compared with a population of RA patients not exposed to anti-TNFα. However, biologics could increase the risk of cutaneous cancers, including melanoma.
