Phase II trial of arsenic trioxide and alpha interferon in patients with relapsed/refractory adult T-cell leukemia/lymphoma.
Human T-cell lymphotropic virus type 1 associated adult T-cell leukemia/lymphoma carries a very poor prognosis due to its intrinsic resistance to chemotherapy. Although zidovudine (AZT) and alpha-interferon (IFN) yield some responses and improve ATL prognosis, alternative therapies are needed. Arsenic trioxide (As) dramatically synergizes with IFN to induce growth arrest and apoptosis of ATL leukemia cells in vitro. These results prompted us to initiate a phase II trial of As/IFN combination in seven patients with relapsed/refractory ATL (four acute and three lymphoma). Four patients exhibited a clear initial response (one complete remission and three partial remissions). Yet, the treatment was discontinued after a median of 22 days because of toxicity (three patients) or subsequent progression (four patients). Six patients eventually died from progressive disease (five patients) or infection (one patient), but the remaining patient is still alive and disease free at 32 months. Pharmacokinetic studies showed that maximum arsenic blood levels (median 0.46 microM) were slowly achieved (8-15 days). In conclusion, arsenic/IFN treatment is feasible and exhibits an anti-leukemia effect in very poor prognosis ATL patients despite a significant toxicity. Future studies should assess the best timing for arsenic therapy: frontline with IFN/AZT or as maintenance after induction.
Hermine
Olivier
O
Department of Hematology, Necker Hospital, Paris, France. hermine@necker.fr
Dombret
Hervé
H
Poupon
Joel
J
Arnulf
Bertrand
B
Lefrère
Francois
F
Rousselot
Phillippe
P
Damaj
Gandhi
G
Delarue
Richard
R
Fermand
Jean Paul
JP
Brouet
Jean Claude
JC
Degos
Laurent
L
Varet
Bruno
B
de Thé
Hugues
H
Bazarbachi
Ali
A
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage*; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D016898:Interferon-alpha / Q000008:administration & dosage*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage*; D011379:Prognosis; D012008:Recurrence; D016896:Treatment Outcome; D015215:Zidovudine / Q000008:administration & dosage
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D001152:Arsenicals; D016898:Interferon-alpha; D010087:Oxides; D015215:Zidovudine; D000077237:Arsenic Trioxide