Susnjar S, Bosnjak S, Radulovic S, Stevanovic J, Gajic-Dobrosavljevic M, Kreacic M
Department of Medical Oncology, Radiology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia.
J BUON. 2007 Apr-Jun;12(2):189-96.
Capecitabine and paclitaxel show high efficacy, non-overlapping toxicity profiles and preclinical synergism, providing the rationale for their combination in metastatic breast cancer (MBC). This dose-escalation study aimed at determining the maximum tolerated dose (MTD) of capecitabine plus paclitaxel in anthracycline-pretreated MBC patients.
Patients with MBC received fl at-dose of oral capecitabine (1,000 mg/m(2) twice daily, days 1-14) plus weekly paclitaxel 60, 75, or 90 mg/m(2), i.v., days 1, 8 and 15, every 3 weeks.
All 11 patients enrolled onto study were evaluable for toxicity and response. Two patients receiving paclitaxel 75 mg/m(2) experienced grade 3 nail toxicity, with grade 3 hand-foot syndrome (HFS) in one patient and grade 2 dermatitis in the other. Although not life-threatening, these were considered unacceptable and the preceding dose level was selected. Eight of 11 patients achieved objective responses.
The recommended regimen is capecitabine 1,000 mg/m(2) twice daily, days 1-14, plus paclitaxel 60 mg/m(2)/week. Escalation of the paclitaxel dose above 60 mg/m(2)/week is not feasible due to severe skin toxicity.
卡培他滨和紫杉醇显示出高效、不重叠的毒性谱以及临床前协同作用，为它们联合用于转移性乳腺癌（MBC）提供了理论依据。本剂量递增研究旨在确定在接受过蒽环类药物预处理的MBC患者中卡培他滨加紫杉醇的最大耐受剂量（MTD）。
MBC患者接受固定剂量的口服卡培他滨（1000mg/m²，每日两次，第1 - 14天）加每周一次的紫杉醇60、75或90mg/m²，静脉注射，第1、8和15天，每3周重复一次。
入组研究的所有11例患者均可进行毒性和疗效评估。两名接受75mg/m²紫杉醇的患者出现3级指甲毒性，其中一名患者出现3级手足综合征（HFS），另一名患者出现2级皮炎。虽然这些情况不危及生命，但被认为不可接受，因此选择了之前的剂量水平。11例患者中有8例获得了客观缓解。
推荐方案为卡培他滨1000mg/m²，每日两次，第1 - 14天，加紫杉醇60mg/m²/周。由于严重的皮肤毒性，将紫杉醇剂量增至60mg/m²/周以上不可行。
