Chua D T, Sham J S, Choy D, Lorvidhaya V, Sumitsawan Y, Thongprasert S, Vootiprux V, Cheirsilpa A, Azhar T, Reksodiputro A H
Department of Radiation Oncology, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
Cancer. 1998 Dec 1;83(11):2270-83.
The aim of this trial was to compare the outcome achieved with neoadjuvant chemotherapy followed by radiotherapy to that achieved with radiotherapy alone for patients with locoregionally advanced undifferentiated or poorly differentiated nasopharyngeal carcinoma (NPC) meeting one of the following criteria: Ho's T3 disease, Ho's N2-N3 disease, or lymph node size > or =3 cm.
Between September 1989 and August 1993, 334 patients were enrolled in the study, with equal numbers of patients randomized to the neoadjuvant chemotherapy arm (CT arm) and the radiotherapy arm (RT arm). Neoadjuvant chemotherapy consisting of 2-3 cycles of cisplatin (60 mg/m2 on Day 1) and epirubicin (110 mg/m2 on Day 1) followed by radiotherapy was given to the CT arm. For radiotherapy, a dose of 66-74 gray (Gy) (median, 71 Gy) was delivered to the primary tumor and 60-76 Gy (median, 66 Gy) to the neck. Two hundred eighty-six eligible patients completed the treatment and were evaluable for treatment response (134 in the CT arm, 152 in the RT arm). All patients were included in the survival analysis based on the intention to treat. The median follow-up was 30 months for the whole cohort and 41 months for the surviving patients.
Analysis of the 334 patients based on the intention to treat showed no significant difference in relapse free survival (RFS) or overall survival (OS) between the 2 treatment arms (3-year RFS rate: 48% in the CT arm vs. 42% in the RT arm, P = 0.45; 3-year OS rate: 78% vs. 71%, P = 0.57). In an efficacy analysis based on only the 286 evaluable patients, a trend of improved RFS favoring the CT arm was observed (3-year RFS rate: 58% vs. 46%, P = 0.053), with again no significant difference in OS (3-year OS rate: 80% vs. 72%, P = 0.21). In the subgroup of 49 patients with bulky neck lymph nodes >6 cm, improved RFS (3-year RFS rate: 63% vs. 28%, P = 0.026) and OS (3-year OS rate: 73% vs. 37%, P = 0.057) were observed, favoring the CT arm.
This multicenter randomized study did not demonstrate any benefit with the addition of cisplatin-epirubicin neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma; therefore routine administration of neoadjuvant chemotherapy to this target group cannot be recommended. Although the overall incidence of recurrence was reduced with the addition of chemotherapy in the efficacy analysis, the overall survival was not affected. A more effective chemotherapy regimen, the selection of an appropriate target group, and the use of an alternative strategy for combining chemoradiotherapy should be explored in future trials.
本试验的目的是比较新辅助化疗后放疗与单纯放疗对符合以下标准之一的局部晚期未分化或低分化鼻咽癌（NPC）患者的治疗效果：何氏T3期疾病、何氏N2 - N3期疾病或淋巴结大小≥3 cm。
1989年9月至1993年8月，334例患者入组本研究，随机分为新辅助化疗组（CT组）和放疗组（RT组），每组患者数量相等。CT组给予2 - 3周期的顺铂（第1天60 mg/m²）和表柔比星（第1天110 mg/m²）新辅助化疗，随后进行放疗。放疗时，给予原发肿瘤66 - 74 Gy（中位剂量71 Gy），颈部60 - 76 Gy（中位剂量66 Gy）。286例符合条件的患者完成治疗并可评估治疗反应（CT组134例，RT组152例）。所有患者均根据意向性治疗纳入生存分析。整个队列的中位随访时间为30个月，存活患者为41个月。
基于意向性治疗对334例患者的分析显示，两组治疗的无复发生存期（RFS）或总生存期（OS）无显著差异（3年RFS率：CT组48%，RT组42%，P = 0.45；3年OS率：78%对71%，P = 0.57）。仅对286例可评估患者进行的疗效分析中，观察到CT组RFS有改善趋势（3年RFS率：58%对46%，P = 0.053），OS仍无显著差异（3年OS率：80%对72%，P = 0.21）。在49例颈部肿大淋巴结>6 cm的亚组中，CT组RFS（3年RFS率：63%对28%，P = 0.026）和OS（3年OS率：73%对37%，P = 0.057）均有改善。
这项多中心随机研究未显示顺铂 - 表柔比星新辅助化疗对局部晚期鼻咽癌患者有任何益处；因此，不建议对该目标人群常规给予新辅助化疗。尽管在疗效分析中化疗的加入降低了总体复发率，但总生存期未受影响。未来试验应探索更有效的化疗方案、合适目标人群的选择以及放化疗联合的替代策略。
