More on the fludarabine angle. Note mention of synergism rather than just additive effect. Thanks berblady.
Int J Cancer 2000 Jan 1;85(1):104-12
Synergistic cytotoxicity of
iodine-131-anti-CD20 monoclonal
antibodies and chemotherapy for
treatment of B-cell lymphomas.
Johnson TA, Press OW
Department of Medicine, University of Washington, Seattle,
WA, USA.
Preliminary clinical trials suggest that iodine-131
((131)I)-labeled anti-CD20 monoclonal antibodies (MAbs)
are effective single agents for the treatment of relapsed
non-Hodgkin's B-cell lymphomas. However, despite high
initial response rates, most patients treated in this manner
will eventually relapse. We hypothesized that regimens
combining (131)I-anti-CD20 antibodies with standard
chemotherapeutic agents may provide synergistic anti-tumor
effects, and may improve the durability of responses in
patients with lymphoma. To identify promising agents for
clinical testing, we assessed the in vitro cytotoxicity of
combinations of (131)I-anti-B1 (anti-CD20) antibody and 8
chemotherapeutic agents using 2 human CD20-expressing
lymphoma cell lines and 2 corroborative assays, the
thiazolyl tetrazolium bromide (MTT) and the Trypan blue
dye exclusion assays. ID(50) isobolographic and dose
modification factor (DMF) analyses were used to classify
interactions between the (131)I-anti-B1 antibody and the
chemotherapeutic agents as supra-additive (synergistic),
additive or sub-additive. Cytarabine and fludarabine were
markedly supra-additive when combined with the
radioimmunoconjugate, with the combination enhancing
cytotoxicity 3. 5- to 5.2-fold over the level expected by
simple addition of the 2 agents (DMFs 3.5-5.2). Etoposide,
doxorubicin and SN-38 were moderately supra-additive
(DMFs 2.0-2.8). Cisplatin and 4-hydroxycyclophosphamide
exhibited merely additive cytotoxicity (DMFs 1.0-1.1).
Thus, combination regimens containing (131)I-labeled
anti-CD20 antibodies and nucleoside analogs or
topoisomerase inhibitors appear particularly attractive for
future clinical trials. Copyright 2000 Wiley-Liss, Inc.
PMID: 10585592, UI: 20054385 |
