ABSTRACT
Invasive aspergillosis is a disease typically related with prolonged neutropenia or the use of corticosteroids. However, the increased use of new therapeutic modalities such as biologic agents that act by blocking specific immune pathways have put more patients at risk for invasive aspergillosis. Most cases of aspergillosis in patients taking monoclonal antibodies have been associated with the use of tumour necrosis factor (TNF)-alpha blockers. However, many more drugs have been implicated, including interleukin-2 inhibitors, and CD52 and CD20 blockers. In this manuscript we review the pathophysiology associated with an increased risk for aspergillosis in these patients, in addition to diagnostic and therapeutic considerations.
Subject(s)
Antibodies, Monoclonal/adverse effects , Aspergillosis/etiology , Alemtuzumab , Antibodies, Monoclonal, Humanized , Antibodies, Neoplasm/adverse effects , Humans , Interleukin-2/antagonists & inhibitors , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
Monoclonal antibodies (MA) are an important group of drugs used in oncology. The objective of this study was to identify MAs used in oncology, and to describe their pharmacological characteristics. This literature review was based on database, index, and library collections. Eight MA were identified, out of which, 37.4% are immunoconjugated, 62.5% are recommended for hematological neoplasms, 75.0% are diluted in saline solution and should not be mixed with other drugs, 100.0% cause digestive side effects, and 87.5% affect the hematopoietic system. In order to guarantee MA's therapeutic efficacy and safety, professionals must fully understand their pharmacological characteristics.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunotherapy , Neoplasms/therapy , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacokinetics , Antibodies, Neoplasm/adverse effects , Antibodies, Neoplasm/immunology , Antibodies, Neoplasm/therapeutic use , Antigens, Neoplasm/immunology , Hematologic Diseases/chemically induced , Hematologic Neoplasms/immunology , Hematologic Neoplasms/therapy , Humans , Immunoconjugates/therapeutic use , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/immunology , Neoplasms/immunologyABSTRACT
Ior egf/r3, a neutralizing monoclonal antibody (mAb) against Epidermal Growth Factor Receptor (EGFR) was generated at the Cuban Institute of Oncology. Immunoscintigraphic studies in 148 patients with this 99-m Technetium (99Tc) labeled mAb, showed a high sensitivity and specificity for in vivo detection of epithelial tumors. To study safety, pharmacokinetic and immunogenicity of ior egf/r3 at high doses, a phase I clinical trial was conducted. Nineteen patients with advanced epithelial tumors received 4 mAb intravenous infusions at 6 dose levels: from 50 to 500 mg. Previously, immunoscintigraphic images using the same mAb labeled with 99Tc were acquired. Blood samples were collected for pharmacokinetic analysis and HAMA response. After mAb therapy, objective response was classified according to WHO criteria. Ior egf/r3 was well tolerated in spite of the high-administered doses. Only a severe adverse reaction consisting of hypotension and lethargy was observed. In 13 patients, selective accumulation of 99Tc-labeled mAb was observed at the site of the primary tumor or the metastasis. Pharmacokinetic analysis revealed that elimination half-life and the area under the time-concentration curve increased linearly with dose. HAMA response was detected in 17 patients. After 6 months of mAb therapy, 4 patients had stable disease. One patient had a tumor partial remission after 3 cycles of ior egf/r3.