Enhanced clearance of leukemic lymphocytes in B-cell chronic lymphocytic leukemia with etodolac

Nardella, Francis A.; LeFevre, Jane A.

doi:10.1182/blood.v99.7.2625

Cited by 13 publications

(10 citation statements)

References 4 publications

(5 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, clinical studies have revealed that ETD chemically induced anticarcinogenic effects on various human carcinoma cell lines [2, 3] and have shown chemopreventive action on biliary carcinogenesis in hamsters [4]. Hence, ETD has revitalized the interest among the researchers for better management of NSAID therapies to widen the scope of therapeutic options for antiarthritis.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Bioavailability and Therapeutic Assessment of Host-Guest Inclusion Phenomena for the Hydrophobic Molecule Etodolac: Pharmacodynamic and Pharmacokinetic Evaluation

Sinha

Amita²,

Goel³

2010

Sci. Pharm.

View full text Add to dashboard Cite

The aim of present investigation was 1) to evaluate the in vivo bioavailability of an Etodolac (ETD)-β-cyclodextrin (β-CD) inclusion complex system prepared by kneading and spray drying techniques in rats, 2) to study the pharmacodynamic parameters in various animal models for analyzing the therapeutic response and, 3) to evaluate the pharmacokinetic profile of the drug administered. Inclusion complexation with β-CD enhanced the solubility of the drug, improved bioavailability and reduced ulcerogenicity of ETD in rats. Pharmacodynamic studies were carried out in normal LACA mice and pharmacokinetic evaluation was done in male Wistar rats. Pharmacokinetic parameters evaluated for the inclusion complexes revealed good correlation. The minimum dose necessary to produce analgesic or anti-arthritic activity was also decreased, indicating that the host-guest strategy that uses β-CD and ETD was very effective and could be successfully employed in the preparation of pharmaceutical formulations of anti-arthritics and analgesics.

show abstract

Section: Introductionmentioning

confidence: 99%

In Vivo Bioavailability and Therapeutic Assessment of Host-Guest Inclusion Phenomena for the Hydrophobic Molecule Etodolac: Pharmacodynamic and Pharmacokinetic Evaluation

Sinha

Amita²,

Goel³

2010

Sci. Pharm.

View full text Add to dashboard Cite

show abstract

“…In addition, antileukemic activity of R-etodolac has been demonstrated in this study by significant reductions in ALC. Together with previous reports that etodolac activity is maintained even after multiple treatments [19], the results of this study may provide a rationale for further investigation of the efficacy of R-etodolac as maintenance therapy or in combination therapy strategies.…”

Section: Discussionmentioning

confidence: 64%

“…It was serendipitously observed that etodolac lowered the malignant lymphocyte counts in a patient with B-CLL who was being treated for arthritis [19]. Further investigation revealed that this activity was unaffected by repeated or prolonged treatment; however, the antileukemic effect of 300 mg of etodolac twice daily (BID) was short-lived, with lymphocyte counts returning to pretreatment levels within 2 weeks of drug withdrawal.…”

Section: Introductionmentioning

confidence: 97%

Phase I study of a novel pro-apoptotic drug R-etodolac in patients with B-cell chronic lymphocytic leukemia

Jensen

Engert

Weißinger³

et al. 2007

Invest New Drugs

View full text Add to dashboard Cite

R-etodolac is a novel pro-apoptotic agent with potential antitumor activity against B-cell chronic lymphocytic leukemia (B-CLL). This phase I clinical trial was conducted to determine the tolerability, safety, and maximum tolerated dose (MTD) of R-etodolac, administered orally twice a day (BID), in patients with B-CLL. Secondary objectives included evaluating clinical response, pharmacodynamic activity (reduction of lymphocytes), and pharmacokinetic (PK) profile. Forty-three patients were enrolled in the study. The most frequently reported adverse events were diarrhea, rash, pruritus, and headache. Increases in alanine aminotransferase (ALT) were also observed. Adverse events were generally mild and self-limiting, although in an apparent dose-response relationship, grade 2 and 3 gastrointestinal toxicities and grade 3 skin toxicities were reported with the highest dose regimens (1,800 and 2,400 mg BID). Hematologic toxicity was rare. The MTD was determined to be 1,200 mg BID. PK results indicated that oral absorption of R-etodolac was rapid (time to maximum concentration ranged from 2 to 4 h), and the half-life ranged from 5 to 7 h. The increase in maximum concentration, however, was not proportional to the increase in dose. R-etodolac significantly reduced absolute lymphocyte count (ALC) in B-CLL patients in a dose-dependent manner up to 1,800 mg BID and caused partial responses in 2 patients. Further study of R-etodolac as a possible new maintenance therapy or as a part of combination therapy of B-CLL appears warranted.

show abstract

“…SDX-101 also has shown to be very active in B-cell chronic lymphocytic leukemia (B-CLL) [42,43]. Case reports demonstrate that B-CLL patients treated with R/S-etodolac showed a drop in the circulating lymphocyte count [44]. Recently, Lu et al have shown that SDX-101 inhibits the transcription of a b-catenin-dependent T-cell factor/lymphoid-enhancing transcription factor receptor gene in HEK293 cells, and inhibits the survival of B-CLL cells in vitro [42].…”

Section: Anti-tumor Effect Of Etodolac and Its Analog Sdx-101mentioning

confidence: 98%

SDX‐308 and SDX‐101, Non‐Steroidal Anti‐Inflammatory Drugs, as Therapeutic Candidates for Treating Hematologic Malignancies Including Myeloma

Lentzsch¹,

Elliott²,

Roodman

2007

Archiv der Pharmazie

View full text Add to dashboard Cite

Non-steroidal anti-inflammatory drugs have been shown to inhibit carcinogenesis in colon cancer, and to induce apoptosis in a variety of tumor cell lines. Some anti-tumor effects are thought to be related to their cyclooxygenase-2-inhibitory activity, but recent studies have shown that non-steroidal anti-inflammatory drugs exert their anti-tumor effect via cyclooxygenase-2-independent mechanism. SDX-308 (CEP-18082) is a non-cyclooxygenase-2-inhibiting indole-pyran analog and is structurally related to SDX-101, an R-enantiomer of etodolac. SDX-308 has a potent anti-myeloma effect and shows synergism in combination with other drugs for the treatment of chronic lymphocytic leukemia. In addition SDX-308 inhibits osteoclast formation and activity and thereby might be an attractive drug for the treatment of diseases with increased osteoclast activity such as osteolytic lesions in multiple myeloma and metastatic carcinomas, as well as osteoporosis. This review covers future application of SDX-308 as an anti-myeloma drug regulating increased osteoclast activity.

show abstract

Enhanced clearance of leukemic lymphocytes in B-cell chronic lymphocytic leukemia with etodolac

Cited by 13 publications

References 4 publications

In Vivo Bioavailability and Therapeutic Assessment of Host-Guest Inclusion Phenomena for the Hydrophobic Molecule Etodolac: Pharmacodynamic and Pharmacokinetic Evaluation

In Vivo Bioavailability and Therapeutic Assessment of Host-Guest Inclusion Phenomena for the Hydrophobic Molecule Etodolac: Pharmacodynamic and Pharmacokinetic Evaluation

Phase I study of a novel pro-apoptotic drug R-etodolac in patients with B-cell chronic lymphocytic leukemia

SDX‐308 and SDX‐101, Non‐Steroidal Anti‐Inflammatory Drugs, as Therapeutic Candidates for Treating Hematologic Malignancies Including Myeloma

Contact Info

Product

Resources

About