Metronomic oral cyclosphosphamide as 3rd line systemic treatment or beyond in patients with inoperable locoregionally advanced recurrent or metastatic nasopharyngeal carcinoma

There is no standard 3rd line or further systemic treatment for patients inoperable locoregionally advanced recurrent/metastatic nasopharyngeal carcinoma (NPC). Oral cyclophosphamide provides a convenient and cheap option for these heavily pretreated patients who have very limited choices of treatment options. We conducted a prospective single-arm open-label study of metronomic oral cyclophosphamide in this setting. Patients with locoregionally advanced recurrent inoperable (rT3/T4, rN2-N3b) or metastatic (rM1) NPC who had good ECOG performance status (PS) (0-2) and had progressed after at least 2 lines of palliative systemic chemotherapy were eligible. They received open-label oral cyclophosphamide between 50mg to 150mg daily dose. Best objective response rate (ORR), disease control rate (DCR), biochemical response assessed by plasma EBV DNA, progression-free survival (PFS), overall survival (OS) and safety profiles were evaluated. Of 56 patients who received cyclophosphamide, 16 and 37 (66.1%) had ECOG performance status (PS) 1 and 2 respectively. 33, 13, 6, 3 and 1 patients received cyclophosphamide as 3rd, 4th, 5th, 6th and 7th line of therapy respectively. After a median follow-up of 8.95 months (range 0.76-58.51), the ORR was 8.9% and the DCR was 57.1% after cyclophosphamide. Biochemical response with 2 consecutive decline in plasma EBV DNA was seen in 10 (17.9%) patients. The median PFS and OS were 4.47 and 9.20 months. Those with PS 1 had a longer median PFS (5.49 months) compared to those with PS 2 (3.75 months, p = 0.011). Univariable (p = 0.021) and multivariable analysis (p = 0.010) revealed that ECOG PS 1 was the only significant prognostic factor of PFS. 16 (28.6%) patients developed 3G3 adverse events, including malaise (5.4%), haematological (8.9%), gastrointestinal (3.6%) and feverish (3.6%) and hemorrhagic (1.8%) events. The median cost of the whole drug treatment was 51.65 USD (1 USD = 7.8 HKD). Oral cyclophosphamide is an acceptable 3rd line or subsequent line systemic therapy for locoregionally advanced recurrent or metastatic NPC with acceptable toxicity and limited financial burden to patients.