Longterm Outcome of Induction Chemotherapy of P-Gemox Regimen Followed By Extensive Involved-Field Radiotherapy(EIFRT) for Newly Diagnosed Stage I/II Extranodal Natural Killer/T-Cell Lymphoma---a Single Center Experience

BACKGROUND: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is an aggressive form of non-Hodgkin lymphoma. up to now, optimal therapeutic  strategies for ENKTL have not been fully defined yet. However, approximately 25-50% patients experience local relapse or systemic failure who receive RT alone. The addition of chemotherapy is emphasized to reduce the risk of recurrence. Therefore, we evaluated efficacy and safety of P-GEMOX regimen in patients with newly diagnosed stage I/II ENKTL.

METHODS: We conducted this pilot study to evaluate the efficacy and safety of pegaspargase combined with gemcitabine and oxaliplatin (P- GEMOX) followed by  extensive involved-field radiotherapy(EIFRT) in patients with stage I/II  ENKTL. We enrolled 56 newly diagnosed stage I/II patients. All patients received P-G GEMOX chemotherapy. The P-GEMOX dosage was as follows: gemcitabine 1000 mg/m² intravenous infusion in 30 minutes on days 1 and 8 ; oxaliplatin 100 mg/m² intravenous infusion in 2 hours on day 1; pegaspargase deep intramuscular injection of 2000 U/m² at two different sites on day 1. The regimen was repeated every 3 weeks. Patients underwent 4 cycles of induction chemotherapy, followed by EIFRT. After achieving complete response (CR), partial response (PR), or stable disease (SD). EIFRT was 56 Gy in 28 fractions over 4 weeks. Primary EIFRT was delivered using 6-MeV linear accelerator using 3-dimensional conformal treatment planning. Clinical target volume (CTV) included gross tumor volume with a margin of at least 20mm and the bilateral nasal cavity, bilateral parasinusess. Planning target volume (PTV) included CTV with a 5mm margin. For stage IIE disease, CTV and PTV also included the involved the cervical lymph node area.

RESULTS: The median follow-up was 35.2 months (range: 10.6-51.4 months). The objective response rates(ORR) of P-G GEMOX regimen was 89.3% (50/56), 35(62.5%) patients achieved CR and 15 (26.8%) patients achieved PR, respectively. After EIFRT, ORR increased to 94.6% (53/56), CR rate increased to 89.3% (50/56). The 4-year overall survival(OS) and progression-free survival(PFS) rate was 90.7¡À4.0% and 89.1¡À4.2% for the whole cohort. The OS and PFS of stage I patients were superior to patients with stage II (Figure1A,B). No treatment-related death was observed. No allergic reactions occurred. Common toxicities (>50%) were neutropenia (80.3%), thrombocytopenia (55.3%), hypoproteinemia (75.0%). Fibrinogen decrease rate was 44.6%. The most common grade III/IV toxicities (>10%) were granulocytosis (23.2%), thrombocytopenia (19.6%) and hypoproteinemia (10.7%).

CONCLUSION: The P-GEMOX regimen followed by radical radiotherapy yielded  very promising longterm survival for patients with  stage I/II ENKTL  with good tolerance. Further investigation of P-GEMOX in a larger series of patients , is required.

Figure 1. Survival for different stage. (A) Overall survival(P=0.056). (B) Progression free survival (P=0.023).

A.                                B.