Abitbol A A, Schwade J G, Lewin A A, Sridhar K, Brandon A H, Markoe A M, Casiano R R, Houdek P V, Serago C, Miller D J
Department of Radiation Oncology, University of Miami, Florida.
Am J Clin Oncol. 1992 Jun;15(3):250-5. doi: 10.1097/00000421-199206000-00014.
Seventeen patients were entered into a Phase I/II trial of concurrent hyperfractionated radiation therapy (7,440 cGy total dose; 120 cGy b.i.d.) combined with constant infusion of 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours for 72 hours) and cisplatin (DDP) (50 mg/m2) for a total of three cycles. Thirteen patients had Stage IV disease; three, Stage III disease; and one, Stage II hypopharyngeal disease. Thirteen of 17 patients had positive cervical lymph nodes, and the mean size of the largest lymph node was 5.5 x 5.1 cm. The patients were not treated with planned adjunctive surgery except for one patient who had a radical neck dissection for massive, rapidly growing cervical adenopathy, which recurred promptly within 1 month before the initiation of protocol therapy. After the initial six patients were entered, mitomycin-C (Mito 8 mg/m2) was added during the second cycle. All the patients completed the planned course of radiotherapy with a median dose of 7,440 cGy and a mean dose of 7,248 cGy except for two patients who died--one from toxicity and the other, suicide. The predominant toxicity was mucositis, which was grade 3/4 in 11 of 15 patients, resulting in an average interruption of radiation therapy of 12 days. Weight loss was significant and was on the average 12% of baseline weight. Hematological toxicity was mild in the 5-FU/DDP group (only one grade 3 toxicity of six) and severe in the 5-FU/DDP/Mito-treated patients (five of eight patients having grade 3/4 toxicity including one leukopenic pneumonitis death). Additional toxicity included one parapharyngeal cellulitis, which responded to antibiotics. Noncompliance with the complex regimen was only seen in three patients. One patient refused b.i.d. radiation therapy, and one patient refused further chemotherapy after the first cycle. Additionally, one patient who had a severe ethanol withdrawal reaction during the first cycle of 5-FU/DDP did not receive further chemotherapy. The complete response rate of both primary site and neck by the protocol regimen alone was 71%. However, two patients, one from each group, did undergo salvage neck dissection, and the locoregional control is currently 73%, with a mean follow-up time of 18.4 months. The feasibility of combining hyperfractionated radiation therapy with aggressive concurrent chemotherapy was demonstrated. The response and local control rate justifies the added toxicity of concurrent chemotherapy and radiation therapy.
17例患者进入了一项I/II期试验，接受同步超分割放射治疗（总剂量7440 cGy；每次120 cGy，每日2次），联合持续输注5-氟尿嘧啶（5-FU）（1000 mg/m²/24小时，共72小时）和顺铂（DDP）（50 mg/m²），共三个周期。13例患者为IV期疾病；3例为III期疾病；1例为II期下咽疾病。17例患者中有13例颈部淋巴结阳性，最大淋巴结的平均大小为5.5×5.1 cm。除1例患者因颈部巨大、快速生长的腺病进行了根治性颈清扫术外，其余患者均未接受计划性辅助手术，该患者在方案治疗开始前1个月内疾病迅速复发。最初6例患者入组后，在第二个周期添加了丝裂霉素-C（丝裂霉素8 mg/m²）。除2例患者死亡（1例死于毒性反应，另1例自杀）外，所有患者均完成了计划的放射治疗疗程，中位剂量为7440 cGy，平均剂量为7248 cGy。主要毒性为黏膜炎，15例患者中有11例为3/4级，导致放射治疗平均中断12天。体重减轻显著，平均为基线体重的12%。5-FU/DDP组血液学毒性较轻（6例中仅1例3级毒性），而5-FU/DDP/丝裂霉素治疗的患者血液学毒性严重（8例患者中有5例为3/4级毒性，包括1例因白细胞减少性肺炎死亡）。其他毒性包括1例咽旁蜂窝织炎，对抗生素治疗有效。仅3例患者未遵守复杂的治疗方案。1例患者拒绝每日2次的放射治疗，1例患者在第一个周期后拒绝进一步化疗。此外，1例患者在5-FU/DDP第一个周期出现严重乙醇戒断反应，未接受进一步化疗。仅采用方案治疗时，原发部位和颈部的完全缓解率为71%。然而，每组各有1例患者接受了挽救性颈清扫术，目前局部区域控制率为73%，平均随访时间为18.4个月。证明了超分割放射治疗与积极同步化疗联合应用的可行性。缓解率和局部控制率证明了同步化疗和放射治疗增加的毒性是合理的。
