Modified VAD and PSC-833 in the treatment of resistant or relapsing chronic lymphocytic leukemia (E4996): a trial of the Eastern Cooperative Oncology Group

Friedenberg, William R; Tallman, Martin S; Brodsky, Isadore; Paietta, Elisabeth; Rowe, Jacob M; Lee, Sandra J; Rowland, Kendrith M; Schnetzer, George W; Reed, John C

doi:10.1016/j.leukres.2003.12.002

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Volume 28, Issue 8 , Pages 813-819, August 2004

Modified VAD and PSC-833 in the treatment of resistant or relapsing chronic lymphocytic leukemia (E4996): a trial of the Eastern Cooperative Oncology Group

William R Friedenberg
- Hematology/Oncology, Guthrie Clinic, One Guthrie Square, Sayre, PA 18840, USA
- Corresponding author. Tel.: +1-570-882-2141; fax: +1-570-882-2010.
Martin S Tallman
- Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University Medical School, 676 North St. Clair Street, Suite 850, Chicago, IL 60611, USA
- Tel.: 1-312-695-6180; fax: 1-312-695-6189.
Isadore Brodsky
- Drexel University College of Medicine, Broad & Vine Street MS412, Philadelphia, PA 19102, USA
- Tel.: 1-215-762-7026; fax: 1-215-762-8857.
Elisabeth Paietta
- Our Lady of Mercy Medical Center, 600 E 233rd Street 6th Fl, Bronx, NY 10466-2604, USA
- Tel.: 1-718-920-9992; fax: 1-718-920-1161.
Jacob M Rowe
- Rambam Medical Center and Technion, Bat Galim, 31096 Haifa, Israel
- Tel.: 972-4-854-2541; fax: 972-4-854-2343.
Sandra J Lee
- Department of Biostatistical Science, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
Kendrith M Rowland Jr.
- Carle Clinic Assoc., 812 W University Ave, Champaign, IL 61820-3922, USA
- Tel.: 1-217-383-3010; fax: 1-217-383-3466.
George W Schnetzer
- 2111 E 26th Street, Tulsa, OK 74114, USA
- Tel.: 1-918-743-8004.
John C Reed
- The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
- Tel.: 1-858-646-3132; fax: 1-858-646-3184.

Received 8 September 2003; accepted 2 December 2003.

Abstract

Background & method: The role of multidrug resistance (MDR) was investigated in patients with relapsed chronic lymphocytic leukemia (CLL). PSC-833 was added to modified VAD (a 4-day infusion of vincristine, doxorubicin, with oral dexamethasone, every 3 weeks), in an attempt to improve the response rate (21%) in a prior study. Laboratory tests to determine MDR and apoptosis proteins were correlated with response. Results: Two of the seven MDR-positive cases and one of the four MDR-negative patients achieved a partial response (no significant difference). No significant correlation with response was found in any of the laboratory tests for apoptosis. Conclusion: VAD plus PSC-833 had the same (21%) partial response rate as a prior ECOG study without PSC-833. No correlation of response with MDR or apoptosis testing was found. Other drug resistance factors must play a significant role in determining the response of relapsed patients with CLL.

Keywords: Chronic lymphocytic leukemia, Multidrug resistance, p-Glycoprotein, PSC-833