Ajani J A, Ilson D H, Daugherty K, Kelsen D P
Department of Gastrointestinal Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030-4095, USA.
Semin Oncol. 1995 Jun;22(3 Suppl 6):35-40.
Systemic chemotherapeutic agents, given either singly or in combination, have not affected the dismal prognosis of patients with metastatic or locoregional unresectable carcinoma of the esophagus. New active agents are needed to improve the outcome for these patients. A phase II study evaluated paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered by 24-hour intravenous infusion with granulocyte colony-stimulating factor support to patients with unresectable locoregional or metastatic carcinoma of the esophagus. Response rate, duration of response, and toxicity were assessed. No prior chemotherapy or biologic therapy was allowed, but radiotherapy to a limited field that did not compromise signal lesion evaluation could have been given. The starting paclitaxel dose was 250 mg/m2 repeated every 21 days. The study group included 44 men and seven women with a median age of 57 years and a median Zubrod performance status of I. Among 51 evaluable patients, one complete response and 15 partial responses (PRs) occurred, for a total response rate of 31%. In addition, 11 (22%) achieved a minor response. Among 33 patients with adenocarcinoma, 12 achieved either a complete response (one patient) or a PR (11 patients), and six patients had a minor response. Four of 18 patients with squamous cell carcinoma had a PR and five (28%) had a minor response. The median duration of PR was 17 weeks (range, 7 to 58 weeks). At a median follow-up of 12+ months, 28 patients are alive, with an actuarial median survival duration of 10.2 months (range, 2 to 20+ months). Paclitaxel was well tolerated. Granulocytopenia was frequent, resulting in 11 hospitalizations in nine patients. Grade 3 neuropathy was observed in three patients. Our data suggest that paclitaxel is active against both adenocarcinoma and squamous cell carcinoma of the esophagus. Plans to study paclitaxel in combination with cisplatin and 5-fluorouracil in this group of patients are under way.
全身化疗药物，无论是单独使用还是联合使用，都未能改变转移性或局部区域不可切除食管癌患者的不良预后。需要新的有效药物来改善这些患者的治疗结果。一项II期研究评估了对不可切除的局部区域或转移性食管癌患者静脉输注24小时紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）并给予粒细胞集落刺激因子支持的疗效。评估了缓解率、缓解持续时间和毒性。不允许之前进行过化疗或生物治疗，但可以对不影响信号病变评估的有限野进行放疗。紫杉醇起始剂量为250mg/m²，每21天重复一次。研究组包括44名男性和7名女性，中位年龄57岁，中位Zubrod体能状态为I级。在51例可评估患者中，出现1例完全缓解和15例部分缓解（PR），总缓解率为31%。此外，11例（22%）达到轻微缓解。在33例腺癌患者中，12例达到完全缓解（1例患者）或PR（11例患者），6例患者有轻微缓解。18例鳞状细胞癌患者中有4例达到PR，5例（28%）有轻微缓解。PR的中位持续时间为17周（范围7至58周）。中位随访12 +个月时，28例患者存活，精算中位生存期为10.2个月（范围2至20 +个月）。紫杉醇耐受性良好。粒细胞减少症很常见，导致9例患者住院11次。3例患者观察到3级神经病变。我们的数据表明，紫杉醇对食管癌的腺癌和鳞状细胞癌均有活性。目前正在计划对该组患者研究紫杉醇联合顺铂和5-氟尿嘧啶的疗效。
