Abstract:Lenalidomide (REVLIMID®) CC-5013 (Celgene, NJ, USA) is approved, in both the USA and Europe, in combination with dexamethasone for the treatment of multiple myeloma patients who have received at least one prior therapy, and is rapidly being accepted worldwide for this condition. Lenalidomide is also approved in the USA and Canada for use in transfusion-dependent anemia in patients with low- and intermediate-1-risk myelodysplastic syndromes associated with del (5q) abnormality with or without additional abnorma… Show more
“…Another group of drugs that has a very significant enhancement with vaccines are the IMiDs [66] derived from thalidomide, notably lenalidomide (Revlimid ® ) and pomalidomide (Pomalyst ® ). These drugs were ini tially developed purely for their ability to inhibit TNF α.…”
Section: Other Chemotherapy/immunotherapy Interactionmentioning
Immunotherapy has usually been considered as an alternative to more traditional modalities. Moreover, it has previously been felt that chemotherapy is inherently immunosuppressive and not suitable for combining with immunotherapy. In this review, the concept of combining different modalities that result in cell death, such as radiotherapy and chemotherapy, with immunotherapy is explored. Tumors actively cause immune suppression which can be reversed by their removal but when this is not possible, enhancing the immune response with nonspecific immune stimulation can enhance the response to other modalities, such as radiotherapy and chemotherapy. Additionally, several chemotherapy agents at low doses selectively inhibit regulatory and suppressor cells.
“…Another group of drugs that has a very significant enhancement with vaccines are the IMiDs [66] derived from thalidomide, notably lenalidomide (Revlimid ® ) and pomalidomide (Pomalyst ® ). These drugs were ini tially developed purely for their ability to inhibit TNF α.…”
Section: Other Chemotherapy/immunotherapy Interactionmentioning
Immunotherapy has usually been considered as an alternative to more traditional modalities. Moreover, it has previously been felt that chemotherapy is inherently immunosuppressive and not suitable for combining with immunotherapy. In this review, the concept of combining different modalities that result in cell death, such as radiotherapy and chemotherapy, with immunotherapy is explored. Tumors actively cause immune suppression which can be reversed by their removal but when this is not possible, enhancing the immune response with nonspecific immune stimulation can enhance the response to other modalities, such as radiotherapy and chemotherapy. Additionally, several chemotherapy agents at low doses selectively inhibit regulatory and suppressor cells.
“…It has been used for the treatment of transfusion-dependent anemia due to low- or intermediate-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities [4, 5], and in combination with dexamethasone for the treatment of multiple myeloma (MM) patients who have received at least one prior therapy [6, 7]. Lenalidomide, as a single agent or in combination with other agents, is also being evaluated for the treatment of newly diagnosed MM, chronic lymphocytic leukemia, non-Hodgkin’s lymphoma and certain solid tumors [8–12]. Fig.…”
PurposeAssessment of the absorption, metabolism and excretion of [14C]-lenalidomide in healthy male subjects following a single oral dose.MethodsSix healthy male subjects were administered a single 25 mg oral suspension dose of [14C]-lenalidomide. Blood (plasma), semen and excreta were collected. Mass balance assessments were done by radioactivity measurements. Metabolite profiling and quantitation were accomplished using liquid chromatography with mass spectrometric and radiochemical detection.Results[14C]-Lenalidomide was rapidly absorbed (Tmax 0.77–1.0 h), and the levels declined with a terminal half-life of approximately 3 h, with similar profiles for total blood and plasma radioactivity as well as plasma lenalidomide. The whole blood to plasma radioactivity exposure levels were comparable, suggesting equal distribution between plasma and blood cells. On average, 94% of the administered radioactivity was recovered within 10 days, with >88% recovered within 24 h. Urinary excretion was the primary route of elimination (90% of radioactive dose), with minor amounts excreted in feces (4%). Semen contained a small amount of the radioactive dose (0.0062%). Lenalidomide was the primary radioactive component in plasma (92% of the [14C]-area under the concentration–time curve) and urine (>90% of the radioactivity in urine). The remaining radioactivity was composed of primarily two metabolites: 5-hydroxy-lenalidomide and N-acetyl-lenalidomide, each accounting for less than 5% of the total radioactivity as well as lenalidomide levels in plasma and excreta.ConclusionsIn summary, following oral administration, lenalidomide is highly absorbed and bioavailable, metabolized minimally, and eliminated predominantly via urinary excretion in the unchanged form in humans.
“…The exploration of the anti-inflammatory, antiangiogenic, anticancer and immunomodulatory activities of thalidomide has prompted the synthesis and study of thalidomide analogs such as lenalidomide and pomalidomide. 6,[42][43][44][45] It has also been used in AIDS therapy.…”
Cyclic imides have been extensively investigated because of the wide range of biological activities they exert, as well as due to their importance as synthetic intermediates. Nowadays, focus has been placed on this important class of compounds for their potential new applications, especially in the area of pharmaceutical chemistry. Consequently, the strategies applied for the synthesis of these compounds have attracted considerable attention. Several innovative methodologies have been developed to obtain and functionalize this class of compounds. The use of microwave heating, which is an environmentally harmless strategy, has been making successful inroads in many chemistry areas, such as organic synthesis. Herein we present an update of the microwave-promoted methods for the synthesis of cyclic imides.
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