Motexafin gadolinium (MGd, Xcytrin®) is a novel anti-cancer drug that selectively concentrates in cancer cells and disrupts redox dependent pathways by targeting oxidative stress related proteins such as thioredoxin reductase and metallothioneins. MGd has been shown to generate reactive oxygen species and induce apoptosis in tumor cells. We initiated a study to evaluate the safety and efficacy of MGd in two B-cell malignancies, relapsed/refractory LG and relapsed/refractory CLL or CLL/small lymphocytic lymphoma (CLL/SLL). MGd was given intravenously (IV) at 6mg/kg/day for 3 days q 2 weeks for LG and 5mg/kg/day for 10 days q 3 weeks for CLL/SLL. Ten patients (pts) with LG (2 grade 1, 5 grade 2, 1 grade 3 follicular, 2 marginal zone), 2 pts with CLL/SLL and 1 pt with CLL have been enrolled. Median age was 64.5 yrs (range 44–77), median prior treatment regimens was 3.5 (range 1–6) and median time from diagnosis to treatment was 52 mo. Many LG pts had failed prior aggressive treatment regimens including: CHOP (4), ICE (1), HyperCVAD(1), auto-bone marrow transplant (1); all failed rituxamab and 6 failed Zevalin. CLL/SLL and CLL pts had failed rituxamab (3), fludarabine (2), and R-CHOP (1). MGd related adverse events included skin and urine discoloration (6 and 4 pts), diarrhea, nausea, vesiculobullous rash, peripheral neuropathy (3 pts each). MGd related ≥gr 3 adverse events included skin rash (3 pts), fatigue, neuropathy, photosensitivity (1 pt each). Importantly, no MGd-related myelosuppression was observed. In 12 evaluable pts, there have been three PRs of 2+, 5+ and 8 months duration (2 follicular, 1 CLL). Two pts had SD (follicular, SLL) one of these had resolution of lymphoma related autoimmune hemolytic anemia. Responses occurred after ≤2 cycles of therapy and were seen in patients after extensive prior treatment (mean 4.3 prior regimens, range 3–7). MGd is a non-myelosuppressive drug with single agent activity in LG and CLL/SLL.
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November 16, 2005
Motexafin Gadolinium (MGd) Has Clinical Activity in Relapsed/Refractory Low Grade Lymphomas (LG) and Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL).
Brad S. Kahl, MD,
Brad S. Kahl, MD
1Dept. of Medicine/Hematology, University of Wisconsin, Madison, WI, USA
Dept. of Medicine/Hematology, University of Wisconsin, Madison, WI, USA; Div. of Oncology, Stanford University, Stanford, CA, USA; Dept. of Hematology, Mayo Clinic, Rochester, MN, USA; Dept. of Clin. Medicine, University of Miami, Miami, FL, USA; Dept. of Medicine/Hematology-Oncology, Northwestern University, Chicago, IL, USA and Pharmacyclics, Inc., Sunnyvale, CA, USA.
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Ranjana Advani, MD,
Ranjana Advani, MD
2Div. of Oncology, Stanford University, Stanford, CA, USA
Dept. of Medicine/Hematology, University of Wisconsin, Madison, WI, USA; Div. of Oncology, Stanford University, Stanford, CA, USA; Dept. of Hematology, Mayo Clinic, Rochester, MN, USA; Dept. of Clin. Medicine, University of Miami, Miami, FL, USA; Dept. of Medicine/Hematology-Oncology, Northwestern University, Chicago, IL, USA and Pharmacyclics, Inc., Sunnyvale, CA, USA.
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Neil Kay, MD,
Neil Kay, MD
3Dept. of Hematology, Mayo Clinic, Rochester, MN, USA
Dept. of Medicine/Hematology, University of Wisconsin, Madison, WI, USA; Div. of Oncology, Stanford University, Stanford, CA, USA; Dept. of Hematology, Mayo Clinic, Rochester, MN, USA; Dept. of Clin. Medicine, University of Miami, Miami, FL, USA; Dept. of Medicine/Hematology-Oncology, Northwestern University, Chicago, IL, USA and Pharmacyclics, Inc., Sunnyvale, CA, USA.
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Izidore S. Lossos, MD,
Izidore S. Lossos, MD
4Dept. of Clin. Medicine, University of Miami, Miami, FL, USA
Dept. of Medicine/Hematology, University of Wisconsin, Madison, WI, USA; Div. of Oncology, Stanford University, Stanford, CA, USA; Dept. of Hematology, Mayo Clinic, Rochester, MN, USA; Dept. of Clin. Medicine, University of Miami, Miami, FL, USA; Dept. of Medicine/Hematology-Oncology, Northwestern University, Chicago, IL, USA and Pharmacyclics, Inc., Sunnyvale, CA, USA.
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Andrew Evens, DO,
Andrew Evens, DO
5Dept. of Medicine/Hematology-Oncology, Northwestern University, Chicago, IL, USA
Dept. of Medicine/Hematology, University of Wisconsin, Madison, WI, USA; Div. of Oncology, Stanford University, Stanford, CA, USA; Dept. of Hematology, Mayo Clinic, Rochester, MN, USA; Dept. of Clin. Medicine, University of Miami, Miami, FL, USA; Dept. of Medicine/Hematology-Oncology, Northwestern University, Chicago, IL, USA and Pharmacyclics, Inc., Sunnyvale, CA, USA.
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Leo Gordon, MD,
Leo Gordon, MD
5Dept. of Medicine/Hematology-Oncology, Northwestern University, Chicago, IL, USA
Dept. of Medicine/Hematology, University of Wisconsin, Madison, WI, USA; Div. of Oncology, Stanford University, Stanford, CA, USA; Dept. of Hematology, Mayo Clinic, Rochester, MN, USA; Dept. of Clin. Medicine, University of Miami, Miami, FL, USA; Dept. of Medicine/Hematology-Oncology, Northwestern University, Chicago, IL, USA and Pharmacyclics, Inc., Sunnyvale, CA, USA.
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Richard A. Miller, MD,
Richard A. Miller, MD
6Pharmacyclics, Inc., Sunnyvale, CA, USA
Dept. of Medicine/Hematology, University of Wisconsin, Madison, WI, USA; Div. of Oncology, Stanford University, Stanford, CA, USA; Dept. of Hematology, Mayo Clinic, Rochester, MN, USA; Dept. of Clin. Medicine, University of Miami, Miami, FL, USA; Dept. of Medicine/Hematology-Oncology, Northwestern University, Chicago, IL, USA and Pharmacyclics, Inc., Sunnyvale, CA, USA.
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See-Chun Phan, MD
See-Chun Phan, MD
6Pharmacyclics, Inc., Sunnyvale, CA, USA
Dept. of Medicine/Hematology, University of Wisconsin, Madison, WI, USA; Div. of Oncology, Stanford University, Stanford, CA, USA; Dept. of Hematology, Mayo Clinic, Rochester, MN, USA; Dept. of Clin. Medicine, University of Miami, Miami, FL, USA; Dept. of Medicine/Hematology-Oncology, Northwestern University, Chicago, IL, USA and Pharmacyclics, Inc., Sunnyvale, CA, USA.
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Blood (2005) 106 (11): 4758.
Citation
Brad S. Kahl, Ranjana Advani, Neil Kay, Izidore S. Lossos, Andrew Evens, Leo Gordon, Richard A. Miller, See-Chun Phan; Motexafin Gadolinium (MGd) Has Clinical Activity in Relapsed/Refractory Low Grade Lymphomas (LG) and Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL).. Blood 2005; 106 (11): 4758. doi: https://doi.org/10.1182/blood.V106.11.4758.4758
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November 16 2005
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