Klaassen U, Wilke H, Müller C, Borquez D, Harstrick A, Seeber S
Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Essen.
Semin Oncol. 1997 Oct;24(5 Suppl 17):S17-58-S17-60.
Our phase II study results demonstrating high efficacy and low toxicity for a weekly schedule of high-dose, 24-hour infusional 5-fluorouracil (5-FU)/leucovorin (LV) in intensively pretreated patients with metastatic breast cancer prompted the addition of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to the regimen for a phase I/II study of outpatient second-line treatment of metastatic breast cancer. That study further prompted the addition of cisplatin to the regimen for first-line treatment. Twenty-eight patients with metastatic breast cancer have been evaluated. Pretreatment comprised adjuvant chemotherapy in 24 of 28 patients, but no prior chemotherapy for metastatic disease. Patients were treated with high-dose 5-FU 2 g/m2 (24-hour infusion) plus LV 500 mg/m2 (2-hour infusion before 5-FU) weekly for 6 weeks (days 1, 8, 15, 22, 29, and 36); in addition, paclitaxel 175 mg/m2 (3-hour infusion) was administered on days 0 and 21 and cisplatin 50 mg/m2 (1-hour infusion) on days 1 and 22 before high-dose 5-FU/LV, repeated every 50 days. Patients were treated as outpatients using Port-a-Cath systems (SIMS Deltec Inc, St Paul, MN) and portable pumps. Neutropenia was common but mild to moderate and of short duration in most patients. No hospitalizations were required because of febrile neutropenia, and no granulocyte colony-stimulating factor support was used. Aside from common total alopecia, nonhematologic toxicities consisted mainly of moderate myalgia, diarrhea, mucositis, and nausea and vomiting. Hand-foot syndrome and peripheral neuropathy were cumulative and occurred most commonly during the third treatment cycle with mild to moderate expression. In 28 patients with bidimensionally measurable disease, 25% (seven of 28) attained a complete response, 57% (16 of 28) achieved a partial response, 11% (three of 28) had stable disease, and 7% (two of 28) had disease progression. Overall response was 82% (95% confidence interval, 66% to 100%). We conclude that the combination of paclitaxel/cisplatin with weekly high-dose infusional 5-FU/LV appears to be effective in the first-line treatment of metastatic breast cancer. Preliminary results must be confirmed by the final analysis of response duration, time to progression, and survival.
我们的II期研究结果表明，对于转移性乳腺癌的强化预处理患者，每周一次高剂量、24小时输注5-氟尿嘧啶（5-FU）/亚叶酸钙（LV）的方案具有高效和低毒的特点，这促使我们在该方案中加入紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿），用于转移性乳腺癌门诊二线治疗的I/II期研究。该研究进一步促使在方案中加入顺铂用于一线治疗。对28例转移性乳腺癌患者进行了评估。28例患者中有24例在预处理时接受过辅助化疗，但此前未接受过转移性疾病的化疗。患者接受高剂量5-FU 2 g/m2（24小时输注）加LV 500 mg/m2（在5-FU前2小时输注），每周一次，共6周（第1、8、15、22、29和36天）；此外，在第0天和第21天给予紫杉醇175 mg/m2（3小时输注），在高剂量5-FU/LV前的第1天和第22天给予顺铂mg/m2（1小时输注），每50天重复一次。患者使用植入式静脉输液港系统（SIMS Deltec公司，明尼苏达州圣保罗）和便携式泵作为门诊患者进行治疗。中性粒细胞减少很常见，但大多数患者为轻度至中度且持续时间短。因发热性中性粒细胞减少无需住院，也未使用粒细胞集落刺激因子支持。除了常见的完全脱发外，非血液学毒性主要包括中度肌痛、腹泻、粘膜炎以及恶心和呕吐。手足综合征和周围神经病变具有累积性，最常见于第三个治疗周期，表现为轻度至中度。在28例具有可二维测量疾病的患者中，25%（28例中的7例）达到完全缓解，57%（28例中的16例）获得部分缓解，11%（28例中的3例）病情稳定，7%（28例中的2例）病情进展。总体缓解率为82%（95%置信区间，66%至100%）。我们得出结论，紫杉醇/顺铂联合每周一次高剂量输注5-FU/LV似乎对转移性乳腺癌的一线治疗有效。初步结果必须通过对缓解持续时间、疾病进展时间和生存情况的最终分析来证实。
