| Abstract | Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are rare, and their standard therapy has not been established. They are Epstein-Barr virus-associated lymphoid malignancies, and tumor cells express P-glycoprotein leading to multidrug resistance of the disease. Patients with stage IV, relapsed or refractory diseases have a dismal prognosis, with survival measured in months only. To develop an efficacious chemotherapeutic regimen, we conducted a dose-escalation feasibility study of a new chemotherapeutic regimen, SMILE, comprising the steroid dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide. The components of SMILE are multidrug resistance-unrelated agents and etoposide. Etoposide shows both in vitro and in vivo efficacy for Epstein-Barr virus-associated lymphoproliferative disorders. Eligible patients had newly diagnosed stage IV, relapsed or refractory diseases after first-line chemotherapy, were 15-69 years of age, and had satisfactory performance scores (0-2). Four dose levels of methotrexate and etoposide were originally planned to be evaluated. At level 1, six patients with extranodal NK/T-cell lymphoma, nasal type, were enrolled. Their disease status was newly diagnosed stage IV (n = 3), first relapse (n = 2), and primary refractory (n = 1). All of the first three patients developed dose-limiting toxicities, and one of them died of sepsis with grade 4 neutropenia. A protocol revision stipulating early granulocyte colony-stimulating factor administration was made. Two out of three additional patients developed dose-limiting toxicities that were all manageable and transient. For the six enrolled patients, the overall response rate was 67% and the complete response rate was 50%. Although its safety and efficacy require further evaluation, we recommend a SMILE chemotherapy dose level of 1 for further clinical studies. |
| Authors | Motoko Yamaguchi, Ritsuro Suzuki, Yok-Lam Kwong, Won Seog Kim, Yuichi Hasegawa, Koji Izutsu, Junji Suzumiya, Takayuki Okamura, Shigeo Nakamura, Keisei Kawa, Kazuo Oshimi
(Affiliation: Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. waniwani at clin.medic.mie-u.ac.jp)
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| Journal | Cancer science
(Cancer Sci)
Vol. 99
Issue 5
Pg. 1016-20
(May 2008)
ISSN: 1349-7006 England |
| PMID | 18294294
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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| Chemical References |
- Etoposide
- Ifosfamide
- Dexamethasone
- Methotrexate
- Asparaginase
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| Topics |
- Adolescent
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, therapeutic use)
- Asparaginase
(administration & dosage, therapeutic use)
- Dexamethasone
(administration & dosage, therapeutic use)
- Etoposide
(administration & dosage, therapeutic use)
- Humans
- Ifosfamide
(administration & dosage, therapeutic use)
- Leukemia, Lymphoid
(drug therapy, prevention & control)
- Lymphoma, Extranodal NK-T-Cell
(drug therapy, prevention & control)
- Methotrexate
(administration & dosage, therapeutic use)
- Middle Aged
- Recurrence
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