Ajani J A, Ilson D H, Daugherty K, Pazdur R, Lynch P M, Kelsen D P
Department of Gastrointestinal Oncology and Digestive Diseases, University of Texas M. D. Anderson Cancer Center, Houston 77030-4095.
J Natl Cancer Inst. 1994 Jul 20;86(14):1086-91. doi: 10.1093/jnci/86.14.1086.
Carcinomas of the esophagus and gastroesophageal junction are uncommon and account for approximately 1% of all malignancies in the United States. Advanced squamous cell carcinoma or adenocarcinoma of these sites remains incurable. The median survival of patients is between 4 and 8 months, and their prognosis has not changed in the past several decades. Undoubtedly, there is an urgent need to develop new effective drugs for patients with carcinoma of the esophagus or the gastroesophageal junction.
Our purpose was to evaluate the response rate, duration of response, and toxic effects in previously untreated patients with unresectable local-regional or metastatic carcinoma of the esophagus who were enrolled in a phase II study of paclitaxel (Taxol).
Fifty-two patients with either metastatic or local-regional unresectable carcinoma of the esophagus were eligible for this study. All patients were premedicated with dexamethasone, cimetidine, and diphenhydramine hydrochloride to prevent allergic reaction. The starting dose of paclitaxel was 250 mg/m2 repeated every 21 days. Patients received 5 micrograms/kg granulocyte-colony stimulating factor (G-CSF) subcutaneously daily 24 hours after the completion of paclitaxel to reduce the duration and severity of granulocytopenia.
Of the 52 patients who were initially enrolled, 50 (44 men and six women) were evaluated for toxic effects and response. Thirty-two had adenocarcinoma, and 18 had squamous cell carcinoma. The median age was 58 years (range, 36-77 years). The median Zubrod performance status was 1 (range, 0-1). The median number of courses was four, and the total number of courses administered was 227. The median dose of paclitaxel was 250 mg/m2 (range, 150-280 mg/m2). Paclitaxel dosage was reduced in 52 (23%) of 227 courses and increased in 15 (7%) of 227 courses. Sixteen (32%) patients achieved either a complete or partial response, and 11 (22%) achieved a minor response. Among 32 patients with adenocarcinoma, 11 (34%; 95% confidence interval [CI] = 18%-50%) had either a complete or partial response and six had a minor response. Five (28%; 95% CI = 7%-49%) of 18 patients with squamous cell carcinoma had a partial response, and five (28%) had a minor response. The median duration of partial response was 17 weeks (range, 7 to > or = 58 weeks). At a median follow-up of 9 months, 32 patients remain alive, with an actuarial median survival duration of 13.2 months (range, 2 to > or = 17.5 months). Paclitaxel followed by G-CSF was very well tolerated.
These data indicate that paclitaxel is an active agent against adenocarcinoma and squamous cell carcinoma of the esophagus.
食管癌和胃食管交界癌并不常见，在美国约占所有恶性肿瘤的1%。这些部位的晚期鳞状细胞癌或腺癌仍然无法治愈。患者的中位生存期在4至8个月之间，并且在过去几十年中其预后并未改变。毫无疑问，迫切需要为食管癌或胃食管交界癌患者开发新的有效药物。
我们的目的是评估纳入紫杉醇（泰素）II期研究的既往未治疗的不可切除局部区域或转移性食管癌患者的缓解率、缓解持续时间和毒性作用。
52例转移性或局部区域不可切除食管癌患者符合本研究条件。所有患者均接受地塞米松、西咪替丁和盐酸苯海拉明预处理以预防过敏反应。紫杉醇起始剂量为250mg/m²，每21天重复一次。患者在紫杉醇输注结束后24小时每天皮下注射5μg/kg粒细胞集落刺激因子（G-CSF）以缩短粒细胞减少的持续时间并减轻其严重程度。
最初纳入的52例患者中，50例（44例男性和6例女性）接受了毒性作用和缓解情况评估。32例为腺癌，18例为鳞状细胞癌。中位年龄为58岁（范围36 - 77岁）。中位Zubrod体能状态为1（范围0 - 1）。中位疗程数为4，总共给予227个疗程。紫杉醇中位剂量为250mg/m²（范围150 - 280mg/m²）。227个疗程中有52个（23%）疗程的紫杉醇剂量降低，15个（7%）疗程的剂量增加。16例（32%）患者达到完全或部分缓解，11例（22%）达到轻微缓解。在32例腺癌患者中，11例（34%；95%置信区间[CI]=18% - 50%）达到完全或部分缓解，6例达到轻微缓解。18例鳞状细胞癌患者中有5例（28%；95%CI = 7% - 49%）达到部分缓解，5例（28%）达到轻微缓解。部分缓解的中位持续时间为17周（范围7至≥58周）。中位随访9个月时，32例患者仍存活，精算中位生存期为13.2个月（范围2至≥17.5个月）。紫杉醇联合G-CSF耐受性良好。
这些数据表明紫杉醇是治疗食管癌腺癌和鳞状细胞癌的有效药物。
