Table 2.
Toxicities of the major regimens in treating ENKTL.
| SMILE (ref. 8) Kwong et al. | SMILE (ref. 10) Yamaguchi M et al. | AspMetDex (ref. 9) Jaccard A et al. | RT-2/3DeVIC (ref. 26) Yamaguchi M et al. | CCRT-VIPD (ref. 27) Kim et al. | CCRT-VIPL (ref. 28) Kim et al. | MESA Xu et al. | |
|---|---|---|---|---|---|---|---|
| Patients | Newly diagnosed or refractory/relapsed, any stage | Newly diagnosed stage IV, relapsed/refractory | Relapsed/refractory, any stage | Newly diagnosed stage IE to IIE | Newly diagnosed stage IE to IIE | Newly diagnosed stage IE to IIE | Newly diagnosed stage IE to IIE |
| Number | 87 | 38 | 19 | 33 | 30 | 30 | 40 |
| Regimen | |||||||
| Methotrexate | 2000 mg/m2 day 1 | 2000 mg/m2 day 1 | 3000 mg/m2 day 1 | 1000 mg/m2 day 1 | |||
| Etoposide: | 100 mg/m2 days 2–4 | 100 mg/m2 days 2–4 | Level 1: 67 mg/m2 days 1–3 Level 2: 100 mg/m2 days 1–3 |
100 mg/m2 days 1–3 | 100 mg/m2 days 1–3 | 100 mg days 2–4 | |
| Dexamethasone | 40 mg days 2–4 | 40 mg days 2–4 | 40 mg days 1–4 | 40 mg days 1–3 | 40 mg days 1–4 | 40 mg days 1–3 | 40 mg days 2–4 |
| l-Asparaginase | 6000 U/m2 days 8, 10, 12, 14, 16, 18, and 20 | 6000 U/m2 days 8, 10, 12, 14, 16, 18, and 20 | 6000 U/m2 days 2, 4, 6, and 8 | 4000 U/m2 days 8, 10, 12, 14, 16, 18, and 20 | Pegaspargase 2500 U/m2 day 4 | ||
| Ifosfamide | 1500 mg/m2 days 2–4 | 1500 mg/m2 days 2–4 | Level 1: 1000 mg/m2 days 1–3 Level 2: 1500 mg/m2 days 1–3 |
1200 mg/m2 days 1–3 | 1200 mg/m2 days 1–3 | ||
| Carboplatin | Level 1:200 mg/m2 day 1 Level 2: 300 mg/m2 day 1 |
||||||
| Cisplatin | 30 mg/m2 weekly during CCRT; 33 mg/m2 days 1–3 after CCRT | 30 mg/m2 weekly for 4 weeks during CCRT | |||||
| G-CSF prophylaxis | Yes | Yes | Yes | No | No | No | No |
| Anti-infection prophylaxis | Yes | Yes | Yes | NR | NR | NR | No |
| Hematological toxicity | |||||||
| Neutropenia | 66.7% (58 cases) | 100.0% (38 cases) | 42.1% (8 cases) | 90.9% (30 cases) | 46.7% (14 cases) | Leukopenia: 80.0% (24 cases) | 52.5% (21 cases) |
| Thrombocytopenia | 41.4% (36 cases) | 63.2% (24 cases) | 5.3% (1 case) | 18.2% (6 cases) | 23.3% (7 cases) | 13.3% (4 cases) | 7.5% (3 cases) |
| Anemia | NR | 50.0% (19 cases) | 21.1% (4 cases) | 24.2% (8 cases) | 26.7% (8 cases) | 10.0% (3 cases) | 12.5% (5 cases) |
| Non-hematological toxicity | |||||||
| Nausea | NR | 13.2% (5 cases) | NR | NR | 3.3% (1 case) | 10.0% (3 cases) | 10.0% (4 cases) |
| Vomiting | NR | 13.2% (5 cases) | NR | NR | 3.3% (1 case) | 0% | 10.0% (4 cases) |
| Diarrhea | NR | 10.5% (4 cases) | NR | NR | 0% | 0% | 0% |
| Hepatotoxicity | 6.9% (6 cases) | Hypoalbuminemia 15.8% (6 cases) Hyperbilirubinemia 10.5% (4 cases) AST elevation 31.6% (12 cases) ALT elevation 31.6% (12 cases) |
15.8% (3 cases) | NR | NR | Transaminase elevation: 10.0% (3 cases) | Hyperbilirubinemia: 10.0% (4 cases) AST/ALT elevation: 7.5% (3 cases) |
| Nephrotoxicity | 1.1% (1 case) | 5.3% (2 cases) | 0% | NR | NR | NR | 0% |
| Allergy | 1.1% (1 case) | 2 allergies, grading unknown | 5.3% (1 case) | NR | NR | NR | 0% |
| Infection | 31% (27 cases) for serious infection, grading unknown | 60.5% (23 cases) | 10.5% (2 cases) | Infection with grade 3 or 4 neutropenia: 12.1% (4 cases); Infection without neutropenia: 6.1% (2 cases) |
Two deaths were associated with infection | NR | 15.0% (6 cases) |
| Mucositis | NR | 13.2% (5 cases) | NR | Mucositis related to radiation: 36.4% (12 cases) | Stomatitis: 0% | Stomatitis during CCRT: 16.7% (5 cases) Stomatitis during chemotherapy: 21.4% (6 cases) |
Mucositis related to radiation:22.5% (9 cases) Mucositis related to chemotherapy: 10.0% (4 cases) |
| Amylase | NR | 18.4% (7 cases) | NR | NR | NR | NR | 7.5% (3 cases, all grade 3 pancreatitis) |
G-CSF, granulocyte-colony stimulating factor.
NR: not reported.
RT: radiotherapy.
CCRT: concurrent chemoradiotherapy.