Lee Victor H F, Kwong Dora L W, Lam Ka-On, Lai Yu-Ching, Li Yun, Tong Chi-Chung, Ho Patty P Y, Chan Wing-Lok, Wong Lai-San, Leung Dennis K C, Chan Sum-Yin, Chan Fong-Ting, Leung To-Wai, Lee Anne W M
Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Medicine (Baltimore). 2017 Apr;96(15):e6518. doi: 10.1097/MD.0000000000006518.
There is no standard third-line or further systemic treatment for patients with inoperable locoregionally advanced recurrent or metastatic nasopharyngeal carcinoma (NPC). Metronomic oral cyclophosphamide provides an acceptable and cheap option for these heavily pretreated patients who had limited choices. We conducted a prospective phase II single-arm open-label study of metronomic oral cyclophosphamide. Patients with locoregionally advanced recurrent inoperable (rT3/T4, rN2-N3b) or metastatic (rM1) NPC who had Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0-2) and had progressed after at least 2 lines of palliative systemic chemotherapy were eligible. They received oral cyclophosphamide between 50 and 150 mg once daily until progressive disease or unacceptable toxicity. Objective response rate (ORR), disease control rate (DCR), biochemical response (two consecutive declines of plasma EBV DNA after treatment), progression-free survival (PFS), overall survival (OS), and safety profiles were evaluated. A total of 56 patients were recruited. Thirty-three, 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 9.95 months (range 1.76-59.51 months), the ORR was 8.9% and the DCR was 57.1%. The median PFS and OS were 4.47 and 9.20 months, respectively. Those with PS 1 had longer median PFS (5.49 months) compared to those with PS 2 (3.75 months, P = .011). Besides, those who had locoregionally recurrent disease had better PFS (8.97 months, 95% CI, 0.53-17.41 months) compared to those who had distant metastases (4.14 months, 95% CI, 2.53-5.75 months, P = .020). Multivariable analysis revealed that PS 1 (vs 2) (P = .020) and locoregional recurrence (vs metastasis) (P = .029) were the only significant independent prognostic factors of PFS. Around 16 (28.6%) patients developed grade ≥3 adverse events, including malaise (5.4%), hematological (8.9%), gastrointestinal (3.6%), feverish (3.6%), and hemorrhagic (1.8%) events. The median cost of the whole drug treatment was 51.65 US dollars (USD) (range 4.15-142.75 USD) (1 USD = 7.8 HK dollars [HKD]). Metronomic oral cyclophosphamide is an acceptable third-line or beyond systemic therapy for locoregionally advanced recurrent or metastatic NPC with acceptable toxicity and limited financial burden.
对于无法手术的局部区域晚期复发或转移性鼻咽癌（NPC）患者，尚无标准的三线或进一步的全身治疗方案。节拍口服环磷酰胺为这些预处理程度高且选择有限的患者提供了一种可接受且廉价的选择。我们开展了一项关于节拍口服环磷酰胺的前瞻性II期单臂开放标签研究。局部区域晚期复发且无法手术（rT3/T4，rN2-N3b）或转移性（rM1）NPC患者，其东部肿瘤协作组（ECOG）体能状态（PS）为（0-2）且在至少2线姑息性全身化疗后病情进展，符合入组条件。他们每日口服一次剂量为50至150毫克的环磷酰胺，直至疾病进展或出现不可接受的毒性反应。评估了客观缓解率（ORR）、疾病控制率（DCR）、生化反应（治疗后血浆EBV DNA连续两次下降）、无进展生存期（PFS）、总生存期（OS）和安全性。共招募了56例患者。分别有33、13、6、3和1例患者将环磷酰胺作为第3、4、5、6和7线治疗药物。中位随访9.95个月（范围1.76 - 59.51个月）后，ORR为8.9%，DCR为57.1%。中位PFS和OS分别为4.47个月和9.20个月。PS为1的患者中位PFS（5.49个月）长于PS为2的患者（3.75个月，P = 0.011）。此外，与远处转移患者（4.14个月，95% CI，2.53 - 5.75个月，P = 0.020）相比，局部区域复发患者的PFS更好（8.97个月，95% CI，0.53 - 17.41个月）。多变量分析显示，PS为1（对比PS为2）（P = 0.020）和局部区域复发（对比转移）（P = 0.029）是PFS仅有的显著独立预后因素。约16例（28.6%）患者发生≥3级不良事件，包括不适（5.4%）、血液学（8.9%）、胃肠道（3.6%）、发热（3.6%）和出血（1.8%）事件。整个药物治疗的中位费用为51.65美元（USD）（范围4.15 - 142.75美元）（1美元 = 7.8港元[HKD]）。节拍口服环磷酰胺是局部区域晚期复发或转移性NPC可接受的三线或更晚期全身治疗方案，毒性可接受且经济负担有限。
