Phase I trial of 7-hydroxystaurosporine and fludararbine phosphate: in vivo evidence of 7-hydroxystaurosporine induced apoptosis in chronic lymphocytic leukemia.

This is a phase I study of 7-hydroxystaurosporine (UCN-01) and fludararbine monophosphate (FAMP) in relapsed lymphoma. UCN-01 alone was administered in cycle 1 and with FAMP in cycles 2-6. FAMP was escalated in cohorts from 1 to 5 days.

Phase I dose-escalation study of recombinant human Apo2L/TRAIL, a dual proapoptotic receptor agonist, in patients with advanced cancer.

Purpose: Apoptosis ligand 2/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL)-a member of the tumor necrosis factor cytokine family-induces apoptosis by activating the extrinsic pathway through the proapoptotic death receptors DR4 and DR5. Recombinant human Apo2L/TRAIL (rhApo2L/TRAIL) has broad potential as a cancer therapy. To the best of our knowledge, this is the first in-human clinical trial to assess the safety, tolerability, pharmacokinetics, and antitumor activity of multiple intravenous doses of rhApo2L/TRAIL in patients with advanced cancer.

A phase I safety and pharmacokinetic study of the death receptor 5 agonistic antibody PRO95780 in patients with advanced malignancies.

Purpose: PRO95780 is a fully human IgG1 monoclonal antibody that triggers the extrinsic apoptosis pathway through death receptor 5. This first-in-human study assessed the safety, tolerability, pharmacokinetics, and any early evidence of efficacy of PRO95780 in patients with advanced malignancies.

Experimental Design: Target concentrations were predicted to occur at 10 mg/kg.

Phase I study of oral lenalidomide in patients with refractory metastatic cancer.

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.

A phase I trial of lenalidomide in patients with recurrent primary central nervous system tumors.

Purpose: Inhibition of angiogenesis represents a promising new therapeutic strategy for treating primary malignant brain tumors. Lenalidomide, a potent analogue of the antiangiogenic agent thalidomide, has shown significant activity in several hematologic malignancies, and therefore we chose to explore its tolerability and activity in patients with primary central nervous system tumors.

Experimental Design: A phase I interpatient dose escalation trial of lenalidomide in patients with recurrent primary central nervous system tumors was conducted.

Cyclooxygenase-2 and angiogenesis in prostate cancer.

Chronic inflammation has been associated with resulting in malignancies in prostate cancer patients. In the May 2005 issue of Clinical Cancer Research, a study by Wang et al. demonstrates a relationship between COX-2 expression and the local chronic inflammation within prostate cancer and the increased angiogenesis.

Immunomodulation of multiple myeloma.

Multiple myeloma is a multi-process disease, and these different processes are responsible for the reduced sensitivity to chemotherapy and radiotherapy, hence the relapse and refractory nature of multiple myeloma. Emphasis is now placed on the hypothesis that myeloma cell growth, inhibition of apoptosis and drug resistance are dependent on immunomodulatory cytokines such as IL-6 and pro-angiogenic factors such as VEGF. In addition to its anti-angiogenic effects, the immunomodulatory properties of thalidomide make it a possible therapy for patients with advanced multiple myeloma.

Determination of SU5416, a novel angiogenesis inhibitor, in human plasma by liquid chromatography.

A high-performance liquid chromatographic (HPLC) assay with UV detection has been developed for the quantitative determination of the antiangiogenic agent SU5416 in human plasma. Sample pretreatment involved a single protein-precipitation step with acetonitrile containing the internal standard, chrysin. Separation of the compounds of interest was achieved on a column packed with HP Zorbax C(8) material (5microm particle size; length: 150mm; i.