Denileukin diftitox for the treatment of cutaneous T-cell lymphoma.
Cutaneous T-cell lymphoma/mycosis fungoides (CTCL/MF) is a rare lymphoproliferative disorder which can present as an indolent or as an aggressive process involving skin, lymph nodes, and blood. In stages IA, IB and IIA, it is usually managed with topical medications and phototherapy. If there is progression despite application of these treatments, or if the patient presents with a higher stage of disease, systemic chemotherapy or retinoids, rexinoids, biologic response modifiers are often necessary. Consequently, patients are often treated with a sequence of modalities and drugs. Denileukin diftitox (DD, Ontak(R)) is a targeted immunotoxin which has biological activity against malignancies expressing the IL-2 receptor. In addition to its unique mechanism of action, DD has a toxicity profile which does not overlap with most commonly used chemotherapeutic agents. CTCL/MF has been found be particularly susceptible to treatment with this agent. This review will describe the development DD, its proposed mechanism of action, the clinical trials which identified its utility in the treatment of CTCL/MF, the common toxicities encountered with this agent, and the management of these toxicities. In addition the incorporation of DD in the sequential treatment of CTCL/MF and data suggesting potential combination therapies employing this novel agent will be discussed.
Kaminetzky
David
D
Division of Hematology/Oncology, New York University School of Medicine, New York, USA.
Hymes
Kenneth B
KB
Eur J Cancer. 1997 Jan;33 Suppl 1:S34-6
9166099
Cytokine. 2004 Nov 7;28(3):109-23
15473953
J Clin Oncol. 2001 Jan 15;19(2):376-88
11208829
Blood. 2002 Aug 15;100(4):1399-403
12149223
J Am Acad Dermatol. 1998 Jul;39(1):63-73
9674399
Cancer Res. 1996 Jun 1;56(11):2590-5
8653702
J Clin Endocrinol Metab. 2006 Jun;91(6):2205-8
16595600
Arch Dermatol. 2007 Jul;143(7):854-9
17638728
Arch Dermatol. 2003 Jul;139(7):857-66
12873880
Clin Exp Dermatol. 2006 Mar;31(2):181-6
16487086
Br J Ophthalmol. 2006 Aug;90(8):1070-1
16854841
Leuk Res. 2002 Dec;26(12):1077-83
12443879
Semin Oncol Nurs. 2006 May;22(2):90-6
16720231
Leuk Lymphoma. 1993 Nov;11(5-6):369-77
8124209
Protein Eng. 1987 Dec;1(6):493-8
3334101
Blood. 1994 Sep 15;84(6):1765-74
8080984
Blood. 1998 Jan 15;91(2):399-405
9427692
Br J Dermatol. 2005 Aug;153(2):324-30
16086743
Am J Hematol. 1998 May;58(1):87-90
9590158
Clin Lymphoma. 2001 Mar;1(4):298-302
11707845
Blood. 2005 Jul 15;106(2):454-7
15811959
Cancer Res. 1989 Jul 15;49(14):4042-6
2786749
J Am Acad Dermatol. 1999 Mar;40(3):418-25
10071312
Blood. 2005 May 15;105(10):3768-85
15692063
J Clin Oncol. 1993 Sep;11(9):1682-90
8355035
J Biol Chem. 1990 Jul 15;265(20):11885-9
2195027
Hematology Am Soc Hematol Educ Program. 2006;:323-30, 513
17124079
Blood. 1992 May 15;79(10):2547-54
1586707
Haematologica. 2004 Nov;89(11):1372-88
15531460
J Exp Med. 1988 Feb 1;167(2):612-22
3126255
Br J Haematol. 2007 Aug;138(4):502-5
17608763
Cancer Res. 1993 Sep 1;53(17):3930-4
8358720
Semin Oncol. 2006 Feb;33(1 Suppl 3):S11-6
16516670