SDX-101 Exerts Additive Effect with Fludarabine, Rituximab

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Leuk Lymphoma. 2006 Dec;47(12):2625-34.

Cytotoxic effect of R-etodolac (SDX-101) in combination with purine

analogs or monoclonal antibodies on ex vivo B-cell chronic

lymphocytic leukemia cells.

Robak P, Linke A, Cebula B, Robak T, Smolewski P.

Department of Hematology, Medical University of Lodz, Lodz, Poland.

R-etodolac (SDX-101) is an isoform of the non-steroidal anti-

inflammatory drug, etodolac, and is currently being tested in phase

II clinical trials for the treatment of refractory B-cell chronic

lymphocytic leukemia (B-CLL).

The aim of this study was to evaluate the cytotoxicity of SDX-101

combined with agents proven to be effective as first-line treatment

of B-CLL: the purine nucleoside analogs, fludarabine (FA) and

cladribine (2-CdA), and the monoclonal antibodies, anti-CD52

(alemtuzumab; ALT) and anti-CD20 (rituximab; RIT).

The cytotoxicity and specific pro-apoptotic effects of the study

drugs on B-CLL cells were assessed in vitro in samples from overall

37 untreated patients. The combinations of SDX-101 with 2-CdA, FA or

RIT exerted additive effects in B-CLL cells, with the following

combination indices (CI): 0.89 for SDX-101 + 2-CdA, 0.95 for SDX-101

+ RIT, and 1.17 for SDX-101 + FA.

The main mechanism of these interactions was caspase-mediated

apoptosis. The SDX-101 plus ALT combination resulted in only sub-

additive cytotoxicity (CI = 1.25).

In conclusion, these data obtained in vitro indicate that addition

of 2-CdA, FA or RIT to SDX-101 significantly enhance cytotoxicity in

B-CLL cells.

PMID: 17169808 [PubMed - in process]