Klaassen U, Harstrick A, Wilke H, Seeber S
Department of Internal Medicine, University of Essen, Germany.
Semin Oncol. 1996 Feb;23(1 Suppl 1):44-7.
Results of phase II studies have demonstrated high efficacy and low toxicity for a weekly schedule of high-dose 5-fluorouracil/folinic acid (5-FU/FA) when given to intensively pretreated patients with metastatic breast cancer. In a phase I/II study of outpatients, we have added paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this regimen in an attempt to improve the results. Patients were treated weekly for 6 weeks (days 1, 8, 15, 22, 29, and 36) with high-dose 5-FU 2.0 g/m2 by 24-hour infusion with FA 500 mg/m2 given as a 2-hour infusion prior to 5-FU. Paclitaxel 175 mg/m2 by 3-hour infusion was administered on days 1 and 22 prior to 5-FU/FA. Each cycle comprised 6 weeks followed by 2 weeks rest; the number of cycles depended on response and toxicity. To date, 40 patients have been entered into this trial during phase II. Pretreatment included adjuvant chemotherapy among 12 patients, prior chemotherapy for metastasis in nine patients, and both adjuvant therapy and treatment for metastasis in 19 patients. Of 24 anthracycline-pretreated patients, 20 had anthracycline-resistant disease. The observed toxicities were of mild to moderate intensity, especially with regard to myelosuppression. Thirty-four patients have been evaluable for response. Response rates included 3% complete response (one of 34 patients) and 50% partial response (17 of 34 patients) for an overall response rate of 53% (95% confidence interval, 37% to 69%). Additionally, 41% (14 of 34 patients) had stable disease and 6% had progressive disease (two of 34 patients). Among 20 anthracycline-resistant patients, 55% responded (11 of 20 patients). The median number of treatment cycles per patient was three (range, one to five); time to maximum response, 2 months (range, 1 to 5 months); and remission duration, 9 months (range, 2 to 17 months). Median time to progression was 10 months (range, 3 to 17 months). In conclusion, the combination of paclitaxel with weekly high-dose 5-FU/FA is well tolerated as second-line treatment of metastatic breast cancer, with high activity, even in patients with anthracycline-resistant disease. The regimen can be administered safely on an outpatient basis.
II期研究结果表明，对于接受过强化预处理的转移性乳腺癌患者，每周给予高剂量5-氟尿嘧啶/亚叶酸（5-FU/FA）具有高效低毒的特点。在一项针对门诊患者的I/II期研究中，我们在此方案中加入了紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿），以期改善治疗效果。患者每周接受6周治疗（第1、8、15、22、29和36天），高剂量5-FU 2.0 g/m²通过24小时静脉输注，FA 500 mg/m²在5-FU之前2小时静脉输注。紫杉醇175 mg/m²通过3小时静脉输注在第1天和第22天5-FU/FA之前给药。每个周期为6周，随后休息2周；周期数取决于反应和毒性。迄今为止，II期试验已纳入40例患者。预处理包括12例患者接受辅助化疗，9例患者先前因转移接受化疗，19例患者既接受辅助治疗又接受转移治疗。在24例接受过蒽环类药物预处理的患者中，20例患有蒽环类药物耐药性疾病。观察到的毒性为轻度至中度，尤其是骨髓抑制方面。34例患者可评估反应。反应率包括3%完全缓解（34例患者中的1例）和50%部分缓解（34例患者中的17例），总反应率为53%（95%置信区间，37%至69%）。此外，41%（34例患者中的14例）疾病稳定，6%疾病进展（34例患者中的2例）。在20例蒽环类药物耐药患者中，55%有反应（20例患者中的11例）。每位患者的中位治疗周期数为3个（范围，1至第5个）；达到最大反应的时间为2个月（范围，1至5个月）；缓解持续时间为9个月（范围，2至17个月）。中位进展时间为10个月（范围，3至17个月）。总之，紫杉醇与每周高剂量5-FU/FA联合使用作为转移性乳腺癌的二线治疗耐受性良好，具有高活性，即使是在蒽环类药物耐药的患者中。该方案可在门诊安全给药。
