Nolè Franco, Catania Chiara, Munzone Elisabetta, Rocca Andrea, Verri Elena, Sanna Giuseppina, Ascione Gilda, Adamoli Laura, Zampino Maria G, Minchella Ida, Goldhirsch Aron
Department of Medicine, European Institute of Oncology, Milan, Italy.
Clin Breast Cancer. 2006 Feb;6(6):518-24. doi: 10.3816/CBC.2006.n.005.
The combination of capecitabine and vinorelbine is a potentially valuable treatment regimen for patients with advanced-stage breast cancer. The drugs are easy to administer and do not cause significant alopecia. In order to identify the spectrum of toxicity of a regimen containing 2 drugs, we conducted an extended phase I study aimed at defining maximum tolerated doses, recommended doses, safety, and efficacy in patients with pretreated advanced-stage breast cancer.
Forty-nine patients with advanced-stage breast cancer were treated with escalating doses of oral capecitabine from 500 mg/m2 to 1375 mg/m2 twice daily on days 1-14 and escalating doses of vinorelbine from 12.5 mg/m2 to 25 mg/m2 intravenously (I.V.) on days 1 and 3 every 3 weeks. Almost all patients (90%) had received >or= 3 previous treatments for metastatic disease (anthracyclines, 76%; 5-flourouracil, 76%; taxanes, 29%).
Dose level 9 (capecitabine 1250 mg/m2 twice daily on days 1-14 and vinorelbine 22.5 mg/m2 I.V. on days 1 and 3) was identified as the maximum tolerated dose. The most frequent clinical adverse events were nausea (78%), asthenia (59%), constipation (51%), mucositis (47%), and hand-foot syndrome (41%). The majority of events were mild to moderate; the only grade 4 clinical adverse events were diarrhea, fever, and thromboembolism, each of which occurred in 1 patient (2%) at dose level 8. Objective confirmed responses were observed in 18 patients (37%), including 1 complete response (2%) and 17 partial responses (35%). Disease was stable in an additional 10 patients (20%), with a median duration of 6.3 months (range, 4-24 months).
The combination of the 2 drugs is very well tolerated and effective, especially considering the previous exposure to chemotherapy. The recommended dose for further phase II studies should be capecitabine 1250 mg/m2 twice daily on days 1-14 and vinorelbine 22.5 mg/m2 I.V. on days 1 and 3.
卡培他滨与长春瑞滨联合用药对于晚期乳腺癌患者而言是一种具有潜在价值的治疗方案。这两种药物易于给药，且不会导致明显的脱发。为了明确含两种药物方案的毒性范围，我们开展了一项扩展的I期研究，旨在确定预处理晚期乳腺癌患者的最大耐受剂量、推荐剂量、安全性及疗效。
49例晚期乳腺癌患者接受治疗，口服卡培他滨剂量从500mg/m²逐步增至1375mg/m²，每日2次，于第1 - 14天给药；长春瑞滨剂量从12.5mg/m²逐步增至25mg/m²，静脉注射，于每3周的第1天和第3天给药。几乎所有患者（90%）既往针对转移性疾病接受过≥3次治疗（蒽环类药物，76%；5-氟尿嘧啶，76%；紫杉烷类，29%）。
第9剂量水平（卡培他滨于第1 - 14天每日2次，剂量为1250mg/m²；长春瑞滨于第1天和第3天静脉注射，剂量为22.5mg/m²）被确定为最大耐受剂量。最常见的临床不良事件为恶心（78%）、乏力（59%）、便秘（51%）、黏膜炎（47%）及手足综合征（41%）。多数事件为轻至中度；仅有的4级临床不良事件为腹泻、发热及血栓栓塞，各有1例患者（2%）在第8剂量水平出现。18例患者（37%）观察到客观确认缓解，包括1例完全缓解（2%）和17例部分缓解（35%）。另有10例患者（20%）疾病稳定，中位持续时间为6.3个月（范围4 - 24个月）。
这两种药物联合使用耐受性良好且有效，尤其考虑到患者既往接受过化疗。进一步II期研究的推荐剂量应为卡培他滨于第1 - 14天每日2次，剂量为1250mg/m²；长春瑞滨于第1天和第3天静脉注射，剂量为22.5mg/m²。
