Antitumor activity of DAB389IL-2 fusion toxin in mycosis fungoides.
BACKGROUND
DAB389IL-2 is a novel fusion toxin that retargets the cytotoxic A-chain of diphtheria toxin to interleukin-2 (IL-2) receptor-expressing tumors.


OBJECTIVE
The purpose of this phase I trial was to study the toxicity, maximum tolerated dose, and clinical efficacy of DAB389IL-2 in IL-2 receptor expressing lymphoproliferative malignancies, including cutaneous T-cell lymphoma.


METHODS
DAB389IL-2 was administered intravenously daily for 5 days every 3 weeks. Dose escalation occurred between patient groups. Patients were monitored for laboratory and clinical toxicity, kinetics, immune response, and clinical efficacy.


RESULTS
Thirty-five patients with cutaneous T-cell lymphoma (including 30 patients with mycosis fungoides) were treated. Previously, conventional therapy had not worked for 34 of the patients. Thirteen patients (37%) achieved an objective response, including a complete response in five patients (14%). Complete response was achieved in patients with extensive erythroderma and tumor stage mycosis fungoides. Adverse events consisted of reversible fever/chills, hypotension, nausea/vomiting, and elevation of hepatic transaminase. Doses of less than 31 microg/kg per day were well tolerated. Clinical responses were observed at all dose levels.


CONCLUSIONS
DAB389IL-2 is well tolerated at doses of less than 31 microg/kg per day, and it induced clinical responses in previously treated mycosis fungoides, providing evidence for the antitumor activity of this molecule.
The University of Alabama at Birmingham, USA.
M N
MN
Saleh
C F
CF
LeMaistre
T M
TM
Kuzel
F
F
Foss
L C
LC
Platanias
G
G
Schwartz
M
M
Ratain
A
A
Rook
C O
CO
Freytes
F
F
Craig
J
J
Reuben
M W
MW
Sams
J C
JC
Nichols
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003873:Dermatitis, Exfoliative / Q000628:therapy; D004167:Diphtheria Toxin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D007022:Hypotension / Q000209:etiology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000922:Immunotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000473:pathology / Q000628:therapy*; D009325:Nausea / Q000209:etiology; D009367:Neoplasm Staging; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D012768:Shivering / Q000502:physiology; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy*; D014839:Vomiting / Q000209:etiology
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox