Gori S, Colozza M, Mosconi A M, Franceschi E, Basurto C, Cherubini R, Sidoni A, Rulli A, Bisacci C, De Angelis V, Crinò L, Tonato M
Medical Oncology Division, Policlinico Hospital, via Brunamonti 51, Perugia 06122, Italy.
Br J Cancer. 2004 Jan 12;90(1):36-40. doi: 10.1038/sj.bjc.6601485.
Synergism between anti-HER2 monoclonal antibody (trastuzumab) and paclitaxel has been shown in vitro and in vivo. In previous experiences, weekly administration of trastuzumab and paclitaxel has shown significant activity in metastatic breast cancer. In this phase II study, we evaluated the activity and the toxicity of this weekly regimen in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer. Between November 1999 and July 2001, 25 patients were treated with trastuzumab (4 mg kg(-1) i.v. loading dose followed by 2 mg kg(-1) i.v. week(-1)) and paclitaxel (60-90 mg m(-2) h(-1) i.v. infusion week(-1)). The treatment was planned to continue until disease progression or prohibitive toxicity; in patients with responsive or stable disease, after 6 months of therapy, the decision to stop paclitaxel while continuing weekly trastuzumab was left to the physicians' judgement. At the median follow-up of 19.6 months (range 9.2-38.1), all patients are evaluable for response and toxicity. We obtained four (16%) complete responses (CR), 10 (40%) partial responses (PR), four (16%) stable diseases and seven (28%) disease progressions. The response rate (CR+PR) was 56% (95% CI, 36.5-75.5%). The median duration of response was 10.4 months (range 4.1-24.2+). Median time to progression was 8.6 months (range 2.5-24.2+). The toxicity was mild; five patients experienced fever and chills during the first infusion of trastuzumab (20%); leukopenia grade 2 was recorded in one patient (4%). Two patients (8%) came off study for grade 3 cardiotoxicity (after 9 and 17 weeks of treatment, respectively): both had already received anthracyclines and taxanes. Onycholysis grade 2 was observed in five patients (20%). These results confirm that weekly administration of trastuzumab and paclitaxel is active in anthracycline- and taxane-pretreated metastatic breast cancer patients HER2-overexpressing. Since cardiac disfunctions grade 3 were observed (8%), we recommend that cardiac function should be monitored in these patients.
抗HER2单克隆抗体（曲妥珠单抗）与紫杉醇之间的协同作用已在体外和体内得到证实。在以往的经验中，每周给予曲妥珠单抗和紫杉醇在转移性乳腺癌中显示出显著活性。在这项II期研究中，我们评估了这种每周方案在接受过蒽环类和紫杉类治疗的HER2过表达转移性乳腺癌患者中的活性和毒性。1999年11月至2001年7月期间，25例患者接受了曲妥珠单抗（静脉注射负荷剂量4mg/kg，随后每周静脉注射2mg/kg）和紫杉醇（静脉输注60 - 90mg/m²/h，每周一次）治疗。治疗计划持续至疾病进展或出现难以耐受的毒性；对于病情缓解或稳定的患者，治疗6个月后，停止紫杉醇治疗而继续每周使用曲妥珠单抗的决定由医生判断。在中位随访19.6个月（范围9.2 - 38.1个月）时，所有患者均可评估疗效和毒性。我们获得了4例（16%）完全缓解（CR）、10例（40%）部分缓解（PR）、4例（16%）病情稳定和7例（28%）疾病进展。缓解率（CR + PR）为56%（95%CI，36.5 - 75.5%）。中位缓解持续时间为10.4个月（范围4.1 - 24.2 + 个月）。中位疾病进展时间为8.6个月（范围2.5 - 24.2 + 个月）。毒性较轻；5例患者在首次输注曲妥珠单抗时出现发热和寒战（20%）；1例患者记录到2级白细胞减少（4%）。2例患者（8%）因3级心脏毒性退出研究（分别在治疗9周和17周后）：两者均已接受过蒽环类和紫杉类治疗。5例患者（20%）观察到2级甲床分离。这些结果证实，每周给予曲妥珠单抗和紫杉醇对接受过蒽环类和紫杉类治疗的HER2过表达转移性乳腺癌患者有活性。由于观察到3级心脏功能障碍（8%），我们建议对这些患者监测心脏功能。
