Gasparini G, Caffo O, Barni S, Frontini L, Testolin A, Guglielmi R B, Ambrosini G
Department of Radiotherapy and Oncology, St Bortolo Medical Center, Vicenza, Italy.
J Clin Oncol. 1994 Oct;12(10):2094-101. doi: 10.1200/JCO.1994.12.10.2094.
To evaluate the efficacy and toxicity of single-agent vinorelbine (VNB), a semisynthetic vinca alkaloid, in patients with breast cancer previously treated with other chemotherapeutic regimens for metastatic disease.
Sixty-seven of 70 patients with assessable disease entered onto the study were assessable. The main characteristics were as follows: median age, 60 years (range, 41 to 77); median performance status (PS; Karnofsky score), 90 (range, 60 to 100); and number of previous chemotherapeutic regimens given--one in 17, two in 27, three in eight, four in two, and five in one patient. The dominant sites of metastasis were viscera in 40, bone in 16, and soft tissues in 11 patients. VNB was administered beginning with the dose of 20 mg/m2 by 60-minute intravenous (iv) infusion weekly, with a dose escalation up to 25 mg/m2 if the first four courses were well tolerated. The treatment was continued until disease progression.
Overall, 845 courses of VNB were given (median, 10; range, eight to 33). Objective responses were as follows: complete response (CR) in three (4.5%), partial response (PR) in 21 (31.2%), stable disease (SD) in 20 (30%), and progressive disease (PD) in 23 patients (34.3%). Twenty-four of 67 assessable patients obtained a major objective response (CR or PR, 36%; 95% confidence interval [Cl], 24% to 47%). Thirty-three percent of patients had a > or = 33% reduction of dose-intensity (DI). The median time to progression was 18 weeks. The drug was active in patients pretreated with either cyclophosphamide, methotrexate, and fluorouracil (CMF) or anthracyclines. The most relevant toxicity observed was myelosuppression: 17 (25%) and 19 patients (28%) had World Health Organization grade III, and six (9%) and six patients (9%) had grade IV leukopenia and granulocytopenia, respectively; two (3%) and two patients (3%) had grade III and IV anemia, respectively. Nonhematologic toxicities were phlebitis (grade II or III in 15 patients), alopecia (grade I or II in 16), nausea and vomiting (grade II or III in 15), diarrhea (grade II in two), constipation (grade II or III in 16), stomatitis (grade II or III in 13), peripheral neuropathy (grade II in seven), and asthenia (grade II in five).
This study shows that VNB is an effective and well-tolerated agent in pretreated patients with advanced breast cancer. This drug does not seem to present cross-resistance with previous CMF or anthracycline regimens. Future clinical trials should be designed to prove whether the inclusion of VNB in combination chemotherapy regimens, or whether an enhancement of its dose-intensity using bone marrow growth factors, is able to improve further the efficacy of this drug in breast carcinoma.
评估半合成长春花生物碱单药长春瑞滨(VNB)对先前接受过其他化疗方案治疗转移性疾病的乳腺癌患者的疗效和毒性。
70例可评估疾病的患者中有67例进入本研究并可进行评估。主要特征如下:年龄中位数为60岁(范围41至77岁);中位体能状态(PS;卡诺夫斯基评分)为90分(范围60至100分);既往接受化疗方案的次数——17例患者接受过1次,27例患者接受过2次,8例患者接受过3次,2例患者接受过4次,1例患者接受过5次。转移的主要部位为:40例患者为内脏,16例患者为骨,11例患者为软组织。VNB以20mg/m²的剂量开始,通过静脉输注60分钟,每周1次给药,如果前4个疗程耐受性良好,则剂量可增至25mg/m²。治疗持续至疾病进展。
总体上,共给予845个疗程的VNB(中位数为10个疗程;范围8至33个疗程)。客观缓解情况如下:3例(4.5%)完全缓解(CR),21例(31.2%)部分缓解(PR),20例(30%)疾病稳定(SD),23例患者(34.3%)疾病进展(PD)。67例可评估患者中有24例获得主要客观缓解(CR或PR,占36%;95%置信区间[CI],24%至47%)。33%的患者剂量强度(DI)降低≥33%。疾病进展的中位时间为18周。该药物对先前接受过环磷酰胺、甲氨蝶呤和氟尿嘧啶(CMF)或蒽环类药物治疗的患者有效。观察到的最相关毒性为骨髓抑制:17例(25%)和19例患者(28%)出现世界卫生组织III级毒性,6例(9%)和6例患者(9%)分别出现IV级白细胞减少和粒细胞减少;2例(3%)和2例患者(3%)分别出现III级和IV级贫血。非血液学毒性包括静脉炎(15例患者为II级或III级)、脱发(16例患者为I级或II级)、恶心和呕吐(15例患者为II级或III级)、腹泻(2例患者为II级)、便秘(16例患者为II级或III级)、口腔炎(13例患者为II级或III级)、周围神经病变(7例患者为II级)和乏力(5例患者为II级)。
本研究表明,VNB对先前接受过治疗的晚期乳腺癌患者是一种有效且耐受性良好的药物。该药物似乎与先前的CMF或蒽环类方案不存在交叉耐药性。未来的临床试验应设计以证明将VNB纳入联合化疗方案中,或使用骨髓生长因子提高其剂量强度是否能够进一步提高该药物在乳腺癌中的疗效。