Multiple-dose pharmacokinetics and safety of CC-5013 in 15 multiple myeloma patients

Wu, Aibin; Scheffler, Michael R.

doi:10.1200/jco.2004.22.14_suppl.2056

Cited by 3 publications

(3 citation statements)

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“…Exposure in rabbits at this dosage is approximately equivalent to lenalidomide exposure in multiple myeloma patients administered a clinical dosage of 25 mg for 28 days (Wu and Scheffler, 2004). At that dosage, AUC 0-24 hr was 2234 ng Â hr/ml and C max was 591 ng/mL.…”

Section: Discussionmentioning

confidence: 97%

Evaluation of the developmental toxicity of lenalidomide in rabbits

Christian

Laskin²,

Sharper

et al. 2007

Birth Defects Research Pt B

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Section: Discussionmentioning

confidence: 97%

Evaluation of the developmental toxicity of lenalidomide in rabbits

Christian

Laskin²,

Sharper

et al. 2007

Birth Defects Research Pt B

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“…Because the approved doses of lenalidomide have been in 2 hematologic malignancies, dosing information and toxicity may not be particularly relevant in patients with refractory solid tumors, with most patients presenting with adequate bone marrow reserve despite advanced stages of disease. Furthermore, in vitro studies using lenalidomide suggest that tumor growth effects were observed at concentrations higher than what is achieved in the clinics, although good immunomodulatory effects have been observed at similar clinical concentrations, as has been indicated by activity of lenalidomide in patients with multiple myeloma and MDS 27 , 28 . These may partly explain why angiogenic effects of lenalidomide monotherapy have not yet been fully realized in solid tumors because these are considered highly angiogenic.…”

Section: Discussionmentioning

confidence: 99%

Phase I Study of Oral Lenalidomide in Patients With Refractory Metastatic Cancer

Dahut

Aragon‐Ching

Woo

et al. 2009

The Journal of Clinical Pharma

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Objectives of this study were to determine the maximum tolerated dose and to characterize the side-effect profile and pharmacokinetics of lenalidomide in patients with advanced refractory solid tumors. Patients were treated on a modified Fibronacci dose-escalation scheme with an oral daily dose of lenalidomide. A total of 45 patients with 8 different tumor types were accrued. Doses administered included 5, 10, and 20 mg continuous daily doses, every 28 days (n=15); later modified to intermittent doses of 15, 20, 25, 30, 35, and 40 mg, 21 days-on and 7 days off schedule, due to observed side effects. Lenalidomide exhibited a linear pharmacokinetics over a wide range doses with the mean half-life of 3.9 hours. The renal function affected lenalidomide clearance, resulting in 50% reduction in patients with mild renal impairment compared wiht patients with normal function (CL/F = 257 mL/min). Stable disease was documented in 12 of 44 evaluable patients, of whom 9 patients had prostate cancer. Most frequent grade 1 and 2 toxicities included fatigue, nausea, pruritus/rash, neutropenia, and neuropathy. Grade 3/4 events were predominantly hematologic. Lenalidomide was well tolerated up to 35 mg/day intermittent dosing schedule at doses higher than previously indicated for hematologic malignancies.

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“…Supplementary to this, the presence of non-viable cells within these colonies suggests a cytotoxic effect (Alley et al, 1982); however, the concentrations of IMiDs used in the soft agar assay were not cytotoxic (Figure 1). Parenthetically, these concentrations were used in all the in vitro studies as they were clinically relevant and achievable in patients (Wu and Scheffler, 2004). These data suggested that the ability to initiate colony development independently of anchorage was not affected, whereas the ability to maintain growth of these colonies was compromised.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of metastatic potential in colorectal carcinoma in vivo and in vitro using immunomodulatory drugs (IMiDs)

et al. 2009

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BACKGROUND: Thalidomide and lenalidomide are FDA approved for the treatment of multiple myeloma and, along with pomalidomide, are being investigated in various other cancers. Although these agents display immunomodulatory, anti-angiogenic and anti-apoptotic effects, little is known about their primary mode of therapeutic action in patients with cancer. METHODS: As part of a continuing research effort, we have investigated the effects of these agents on the metastatic capacity of murine colorectal cancer cell lines both in vivo and in vitro. Allied to these, we have studied their effects on the molecular pathways associated with metastasis. RESULTS: Results indicate that thalidomide, lenalidomide and pomalidomide significantly inhibit the metastatic capability of colorectal carcinoma cells. Anchorage-independent growth, used as a coarse indicator of transformation, was significantly reduced, as were migratory capacity and invasive competence. In addition, an in vivo experimental metastasis model also showed that treatment with the drugs resulted in a significantly lower number of metastatic pulmonary nodules relative to control mice. Allied to these cellular and phenotypic changes were alterations in molecular markers of metastasis and in intracellular signalling competency. CONCLUSIONS: These results provide evidence that in addition to their immunomodulatory effects, thalidomide, lenalidomide and pomalidomide can impair the metastatic capacity of tumours, and that this mechanism may involve alterations to cell signalling functionality.

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Multiple-dose pharmacokinetics and safety of CC-5013 in 15 multiple myeloma patients

Cited by 3 publications

References 0 publications

Evaluation of the developmental toxicity of lenalidomide in rabbits

Evaluation of the developmental toxicity of lenalidomide in rabbits

Phase I Study of Oral Lenalidomide in Patients With Refractory Metastatic Cancer

Inhibition of metastatic potential in colorectal carcinoma in vivo and in vitro using immunomodulatory drugs (IMiDs)

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