Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL).
Adult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-kappaB activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferon-alpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogene-targeted cancer therapy.
Immunology Research Centre, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Ghada
G
Kchour
Mahdi
M
Tarhini
Mohamad-Mehdi
MM
Kooshyar
Hiba
H
El Hajj
Eric
E
Wattel
Mahmoud
M
Mahmoudi
Hassan
H
Hatoum
Hossein
H
Rahimi
Masoud
M
Maleki
Houshang
H
Rafatpanah
S A Rahim
SA
Rezaee
Mojtaba Tabatabaei
MT
Yazdi
Abbas
A
Shirdel
Hugues
H
de Thé
Olivier
O
Hermine
Reza
R
Farid
Ali
A
Bazarbachi
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003875:Drug Eruptions / Q000209:etiology; D004357:Drug Synergism; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects; D011533:Proviruses / Q000302:isolation & purification; D012074:Remission Induction; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects
D001152:Arsenicals; D016898:Interferon-alpha; D010087:Oxides; D015215:Zidovudine; D000077237:Arsenic Trioxide