Calais G, Dorval E, Louisot P, Bourlier P, Klein V, Chapet S, Reynaud-Bougnoux A, Huten N, De Calan L, Aget H, Le Floch O
Clinique d'Oncologie et Radiothérapie, Centre Hospitalier et Universitaire de Tours, France.
Int J Radiat Oncol Biol Phys. 1997 Jul 1;38(4):769-75. doi: 10.1016/s0360-3016(97)00077-1.
Radiotherapy (RT) and concomitant chemotherapy (CT) is the standard treatment for non resectable esophageal cancer. Usual total radiation dose is 50 Gy. In order to enhance local control rate a Phase II study was initiated to evaluate the feasibility of a combined treatment with an external radiation dose of 60 Gy and three cycles of concomitant CT, using the three main active drugs (CDDP, 5 FU and MMC), followed by a high dose rate (HDR) brachytherapy delivering 10 Gy.
Fifty-three patients, 48 men and 5 women, were entered in this study. Stages were evaluated with CT scan and with endoscopic sonography. Fifteen were Stage IIB, 38 Stage III. Treatment consisted of conventional fractionated RT to a total dose of 60 Gy delivered with 2 Gy per fraction, one fraction per day and five fractions per week. The CT regimen was a combination of Cisplatinum (CDDP) 20 mg/m2 and 5 Fluorouracil (5FU) 600 mg/m2 continuous infusion, from days 1-4 Mitomycin C (MMC) was given at 6 mg/m2 on day 1. Three cycles were administered on days 1, 22, and 43. Brachytherapy was delivered one week after the end of external radiation therapy.
Full radiation therapy dose was delivered for 94% of the patients. CT compliance, evaluated on the mean relative dose-intensity was 85% for CDDP, 81% for 5FU and 51% for MMC. Overall grade 3 and 4 WHO toxicity rates were 23% and 7%, respectively. Haematologic toxicity was the most limiting factor. One patient died from treatment toxicity. Local control rate at one year was 74%. Three-year actuarial survival rate was 27%. Distant metastasis was the main cause of treatment failure. Swallowing score was good for 75% of the patients. Stage, performance status and weight loss were prognostic factors.
This regimen with high dose RT, HDR brachytherapy and concomitant CT is feasible; however, a high level of haematologic toxicity was observed with the CDDP, 5FU and MMC regimen. Despite a poor compliance with CT, treatment results are very encouraging for patients with locally advanced disease.
放射治疗（RT）联合同步化疗（CT）是不可切除食管癌的标准治疗方法。通常的总辐射剂量为50Gy。为提高局部控制率，开展了一项II期研究，以评估外照射剂量60Gy联合三个周期同步CT（使用三种主要活性药物：顺铂、5-氟尿嘧啶和丝裂霉素C），随后进行高剂量率（HDR）近距离放疗给予10Gy剂量的联合治疗的可行性。
本研究纳入53例患者，其中48例男性，5例女性。通过CT扫描和内镜超声评估分期。15例为IIB期，38例为III期。治疗包括常规分割放疗，总剂量60Gy，每次分割剂量2Gy，每天1次，每周5次。CT方案为顺铂（CDDP）20mg/m²和5-氟尿嘧啶（5FU）600mg/m²持续输注，第1 - 4天给药，丝裂霉素C（MMC）在第1天给予6mg/m²。在第1、22和43天进行三个周期的治疗。近距离放疗在体外放疗结束后一周进行。
94%的患者完成了全部放疗剂量。以平均相对剂量强度评估的CT依从性，顺铂为85%，5-氟尿嘧啶为81%，丝裂霉素C为51%。WHO 3级和4级毒性的总体发生率分别为23%和7%。血液学毒性是最主要的限制因素。1例患者死于治疗毒性。一年的局部控制率为74%。三年精算生存率为27%。远处转移是治疗失败的主要原因。75%的患者吞咽评分良好。分期、体能状态和体重减轻是预后因素。
这种高剂量RT、HDR近距离放疗联合同步CT的方案是可行的；然而，观察到顺铂、5-氟尿嘧啶和丝裂霉素C方案存在高水平的血液学毒性。尽管CT依从性较差，但对于局部晚期疾病患者，治疗结果非常令人鼓舞。
