Kellokumpu-Lehtinen Pirkko-Liisa, Sunela Kaisa, Lehtinen Ilari, Joensuu Heikki, Sjöström-Mattson Johanna
Department of Oncology, Tampere University Hospital, Finland.
Clin Breast Cancer. 2006 Dec;7(5):401-5. doi: 10.3816/cbc.2006.n.057.
Few overlapping toxicities and oral formulations make capecitabine plus oral vinorelbine an attractive new combination for treating patients with breast cancer. An all-oral regimen minimizes inconvenience for the patient and saves medical resources.
To determine the recommended dose for this all-oral combination, we conducted a phase I study in 21 patients with metastatic breast cancer after failure of previous chemotherapy with anthracylines and/or taxanes for advanced disease. Capecitabine 1000 mg/m2 twice daily was given on days 2-7 and 9-14. Vinorelbine was administered at escalating doses of 40-80 mg/m2 on days 1 and 8 every 3 weeks. Dose escalation of vinorelbine was performed in cohorts of 3 patients, but the dose of vinorelbine could also be increased to the next level in the same patient after 3 cycles if there were no dose-limiting toxicities. In total, 173 cycles were administered (median, 8 cycles; range 1-21+ cycles).
Treatment was well tolerated: there were no grade 4 toxicities, and the only grade 3 toxicities in > 1 cycle were hand-foot syndrome and neutropenia (2% of cycles each). The maximum tolerated dose could not be determined using predefined criteria. However, in this heavily pretreated patient population, intrapatient vinorelbine dose escalation > 60 mg/m2 was rarely achieved. Thus, we considered vinorelbine 60 mg/m2 to offer the best dose level-toxicity ratio. At this dose, grade 3 toxicities occurred in only 7% of the 58 cycles administered. Among 19 evaluable patients, 7 exhibited response or stable disease lasting > 6 months, giving a clinical benefit rate of 37%. Duration of response in the 2 responding patients was 5 months and > 16 months.
The all-oral combination of capecitabine/vinorelbine is well tolerated and active in heavily pretreated patients. Oral vinorelbine 60 mg/m2 is recommended in combination with capecitabine 1000 mg/m2 twice daily for further evaluation.
卡培他滨联合口服长春瑞滨的毒性重叠较少且有口服制剂，使其成为治疗乳腺癌患者的一种有吸引力的新联合方案。全口服方案可将患者的不便降至最低并节省医疗资源。
为确定这种全口服联合方案的推荐剂量，我们对21例转移性乳腺癌患者进行了一项I期研究，这些患者之前使用蒽环类药物和/或紫杉烷类药物治疗晚期疾病失败。卡培他滨1000mg/m²，每日两次，于第2 - 7天和第9 - 14天给药。长春瑞滨每3周在第1天和第8天以40 - 80mg/m²的递增剂量给药。长春瑞滨的剂量递增以3例患者为一组进行，但如果没有剂量限制性毒性，同一患者在3个周期后长春瑞滨剂量也可升至下一级别。总共进行了173个周期（中位数为8个周期；范围1 - 21 +个周期）。
治疗耐受性良好：无4级毒性，且在超过1个周期中仅有的3级毒性为手足综合征和中性粒细胞减少（各占周期数的2%）。无法使用预定义标准确定最大耐受剂量。然而，在这个经过大量预处理的患者群体中，很少能实现患者内长春瑞滨剂量递增超过60mg/m²。因此，我们认为长春瑞滨60mg/m²提供了最佳的剂量水平 - 毒性比。在此剂量下，在给药的58个周期中仅有7%出现3级毒性。在19例可评估患者中，7例表现出缓解或疾病稳定持续超过6个月，临床获益率为37%。2例缓解患者的缓解持续时间分别为5个月和超过16个月。
卡培他滨/长春瑞滨全口服联合方案耐受性良好，在经过大量预处理的患者中具有活性。建议口服长春瑞滨60mg/m²与卡培他滨1000mg/m²每日两次联合用于进一步评估。
