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Drug resistance in multiple myeloma
P Sonneveld1, H M Lokhorst, P Vossebeld
1Department of Hematology, University Hospital Rotterdam, Dijkzigt, The Netherlands. sonneveld@haed.azr.nl
Seminars in Hematology
|December 31, 1997
Summary
Multidrug resistance (MDR) hinders multiple myeloma treatment. Noncytotoxic modulators show promise in reversing MDR by targeting P-glycoprotein (P-gp), potentially improving patient outcomes.
Area of Science:
- Oncology
- Pharmacology
Background:
- Multidrug resistance (MDR) is a significant challenge in multiple myeloma treatment.
- Key MDR mechanisms include P-glycoprotein (P-gp) and lung-resistance protein (LRP) expression, and Bcl-2 mediated apoptosis suppression.
- Chemotherapy exposure can exacerbate MDR emergence in multiple myeloma.
Purpose of the Study:
- To investigate the clinical efficacy of noncytotoxic modulators in reversing MDR in multiple myeloma.
- To evaluate P-gp modulators like verapamil, cyclosporin A (CsA), and PSC 833 for MDR reversal.
Main Methods:
- Phase I/II clinical trials were conducted to assess MDR reversal agents.
- Co-administration of MDR modulators with chemotherapeutic agents was studied.
Main Results:
- Preliminary results suggest that P-gp modulation can reverse MDR in clinical settings.
- Coadministration of MDR modulators with chemotherapy impacts drug pharmacokinetics.
Conclusions:
- Noncytotoxic P-gp modulators offer a potential strategy for overcoming MDR in multiple myeloma.
- Further Phase II and III trials are ongoing to confirm efficacy in hematologic malignancies.