Petry V, Gagliato D M, Leal A I C, Arai R J, Longo E, Andrade F, Ricci M D, Piato J R, Barroso-Sousa R, Hoff P M, Mano M S
Divisão de Oncologia Médica, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Núcleo de Mastologia, Hospital Sírio Libanês, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2015 May;48(5):479-85. doi: 10.1590/1414-431X20144354. Epub 2015 Mar 6.
Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2- (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m(2) during 8 weeks followed by weekly doxorubicin at 24 mg/m(2) for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.
在乳腺癌（BC）治疗中，新辅助化疗相较于辅助化疗策略具有实际和理论上的优势。此外，节拍式给药具有更良好的毒性特征。本研究考察了新辅助节拍式化疗在局部晚期BC的两个队列[HER2阳性（TraQme）和HER2阴性（TAME）]中的可行性。前瞻性纳入了20例患者（TraQme组，n = 9；TAME组，n = 11）。两个队列均在8周内每周接受100 mg/m²的紫杉醇治疗，随后在9周内每周接受24 mg/m²的阿霉素治疗，并联合每日100 mg（固定剂量）的口服环磷酰胺。HER2阳性队列每周接受曲妥珠单抗治疗。该研究因安全问题中断。TAME队列中36%的患者以及TraQme队列的所有患者患有III期BC。值得注意的是，TraQme队列中33%的患者和TAME队列中66%的患者肿瘤组织显示激素受体阳性。TraQme和TAME队列中患者的病理完全缓解率分别为55%和18%。与TAME队列相比，TraQme队列中的患者在诊断时BC分期更晚、病理分级更高，且更多肿瘤缺乏激素受体表达。毒性特征也有所不同。TraQme队列中有2例患者发生肺炎，而在TAME队列中我们观察到更多血液学毒性和手足综合征。本试验评估的新辅助节拍式化疗方案在实现肿瘤反应方面非常有效，尤其是在HER2阳性队列中。肺炎是该组中观察到的一种严重且意外的不良事件。有必要进行进一步更大规模的随机试验，以评估节拍式化疗与曲妥珠单抗治疗之间的关联。
