Concurrent Radiation and ESHAP Regimen in Localized Extranodal NK/T-Cell Lymphoma Nasal Type, Phase II French Study

Background: Front-line radiation combined with chemotherapy is now widely used in patients with localized extranodal NK/T lymphoma nasal type. However, modalities of the chemoradiotherapy combination and chemotherapy drug choices remain unknown. We report here the safety and efficacy of a concurrent chemoradiotherapy (CCRT) using an ESHAP (Etoposide Cisplatin Aracytine Methylprednisolone) modified regimen delivered during two monthly courses of radiotherapy.

Patients and Methods: Front-line radiation (40 to 52.2 Gy) was given concurrently with two cycles of a modified ESHAP chemotherapy, every four weeks. Considering the radio-sensitizing effect of cisplatin, ESHAP regimen was modified splitting the total dose of cisplatin on five consecutive days, instead of four days. Chemotherapy regimen consisted in etoposide 75 mg/m²/d days 1 to 3, cisplatin 20 mg/m²/d days 1 to 5, aracytine 1 g/m²/d days 1 and 2, dexamethasone 20 mg days 1 to 4. Patients who reached a response after the CCRT were planned to receive 3 courses of additional ESHAP alone every four weeks. Bi-weekly blood tests and clinical examination according to the Radiation Therapy Oncology Group guidelines were performed to assess acute toxicity. The tumour response was assessed using the Cheson 2007 International Harmonization Project response criteria, with CT-scan performed after two cycles of CCRT, at the end of the treatment then every 6 months.

Results: Eleven patients were enrolled between January 2004 and December 2013 in Gustave Roussy Cancer Center. Median age was 63 (range 15-86) years. Eight patients had stage IE nasal lymphoma and three had stage IIE. Four out 11 (36%) patients had B symptoms. All patients except one, were treated for a newly localized extranodal NK/T lymphoma nasal type diagnosis. All patients received the CCRT scheduled. Median of additional ESHAP alone given was 2 (range 0-3); eight out of the 11 (73%) patients received a reduced number of additional ESHAP than scheduled. The reasons for reduction in number of ESHAP cycles were hematological toxicity (n = 7) and insufficient tumor response (n = 1). All patients except one (91%), achieved a complete remission. All patients except one (91%), experienced grade 3-4 hematological toxicity. Main non hematological grade 3-4 toxicity was mucositis in 5 out of 11 (46%) of cases. With a median follow-up of 44 months, three patients died. Deaths were related to lymphoma relapse (n=1), sepsis (n=1) and cardiovascular event (n=1), and occurred 12, 4 and 7 months after the end of CCRT-ESHAP treatment, respectively.

Conclusion: With an optimal management of specific toxicities induced by this modality of treatment, concurrent chemoradiotherapy with ESHAP modified regimen for localized NK/T lymphoma nasal type demonstrates high efficacy.