Ajani J A, Roth J A, Ryan M B, Putnam J B, Pazdur R, Levin B, Gutterman J U, McMurtrey M
Department of Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030-4095.
J Clin Oncol. 1993 Jan;11(1):22-8. doi: 10.1200/JCO.1993.11.1.22.
The curative resection rate in patients with potentially resectable carcinoma of the esophagus is approximately 55% and their median survival time is 11 months. Preoperative chemotherapy with high doses of chemotherapeutic agents was used to evaluate clinical and pathologic responses, curative resection rate, toxicity, and survival. Colony-stimulating factor (CSF) was added to reduce the severity of myelosuppression.
Twenty-six consecutive assessable patients with potentially resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative courses of intensive chemotherapy (etoposide, doxorubicin, and cisplatin [EAP]) with granulocyte-macrophage CSF (GM-CSF). Additional three conventional-dose postoperative chemotherapy courses without GM-CSF were given to patients who responded to preoperative chemotherapy.
A median of three courses (range, one to six), were administered. Of 27 patients, 26 were assessable for response to preoperative EAP; 13 (50%) achieved a major response. Among 23 patients who underwent surgery, 15 (65%) had a curative resection (58% of 26 assessable patients); none of the patients had a pathologic complete response, but two patients had only microscopic carcinoma in the resected specimen. Six patients had carcinoma present at the resection margins and received postoperative radiotherapy. Two patients were found to have liver metastases at exploration. At a median follow-up of 22 months, the median survival of 26 patients was 12.5 months (range, 2 to 32 +). Fourteen patients died of their carcinoma; two patients died of treatment-related causes; one died of an unrelated CNS arterial malformation; and the causes of death in two patients remain unknown. Seven patients are alive with no evidence of relapse. Major toxicities of this regimen included severe myelosuppression, nausea and vomiting, infections, and severe constitutional symptoms related to GM-CSF. However, subcutaneous injection of GM-CSF was well tolerated.
High-dose EAP is active against locoregional adenocarcinoma of the esophagus and gastroesophageal junction but can be associated with significant toxicity. Although this strategy remains attractive and needs to be developed further, less toxic and more effective regimens need to be identified.
潜在可切除的食管癌患者的根治性切除率约为55%，其平均生存时间为11个月。采用高剂量化疗药物进行术前化疗，以评估临床和病理反应、根治性切除率、毒性和生存率。添加集落刺激因子（CSF）以减轻骨髓抑制的严重程度。
26例连续可评估的潜在可切除食管腺癌或胃食管交界腺癌患者接受了两个术前疗程的强化化疗（依托泊苷、阿霉素和顺铂[EAP]）及粒细胞-巨噬细胞集落刺激因子（GM-CSF）治疗。对术前化疗有反应的患者术后再给予三个常规剂量且无GM-CSF的化疗疗程。
平均给予三个疗程（范围为1至6个疗程）。27例患者中，26例可评估术前EAP的反应；13例（50%）获得主要反应。23例接受手术的患者中，15例（65%）进行了根治性切除（26例可评估患者中的58%）；无患者达到病理完全缓解，但2例患者切除标本中仅存在微小癌。6例患者切除边缘有癌组织，接受了术后放疗。2例患者在探查时发现有肝转移。中位随访22个月时，26例患者的中位生存期为12.5个月（范围为2至32 +）。14例患者死于癌症；2例患者死于治疗相关原因；1例死于无关的中枢神经系统动脉畸形；2例患者的死亡原因不明。7例患者存活且无复发迹象。该方案的主要毒性包括严重的骨髓抑制、恶心和呕吐、感染以及与GM-CSF相关的严重全身症状。然而，皮下注射GM-CSF耐受性良好。
高剂量EAP对食管和胃食管交界的局部区域腺癌有效，但可能伴有显著毒性。尽管该策略仍然具有吸引力且需要进一步发展，但需要确定毒性更低且更有效的方案。
