Kouloulias Vassilios E, Dardoufas Costas E, Kouvaris John R, Gennatas Costas S, Polyzos Aris K, Gogas Helen J, Sandilos Panagiotis H, Uzunoglu Nikolaos K, Malas Elias G, Vlahos Lambros J
Radiotherapy Department, Areteion University Hospital, Athens.
Clin Cancer Res. 2002 Feb;8(2):374-82.
This is the first study to evaluate the tolerability and activity of liposomal doxorubicin (Caelyx; Schering-Plough Pharmaceuticals) < or =60 mg/km(2) in patients with locally recurrent breast cancer, when administered in conjunction with reirradiation and local hyperthermia treatment.
Fifteen female patients, who had undergone a radical mastectomy and conventional radiotherapy (60 Gy) in the front chest wall, were entered on a multimodal protocol consisting of initial treatment with radiotherapy and a monthly infusion of liposomal doxorubicin < or =60 mg/m(2) in conjunction with local hyperthermia treatment. All patients received reirradiation up to a total dose of 30.6 Gy (1.8 Gy/fraction, 5 days a week). To evaluate the drug's safety, the first 5 patients initially received a dose of 40 mg/m(2) liposomal doxorubicin, which was then escalated to 60 mg/m(2). The other 10 patients received 60 mg/m(2) for all six cycles of chemotherapy. Hyperthermia (HT) was produced in the region of interest (ROI) using waveguides at a frequency of 433 MHz. The RSS was obtained from the curves representing the change in the ROI's surface with time for each patient, as fitted by linear regression. Linear regression analysis was used to study the relationship between the time interval from liposomal doxorubicin infusion to HT and the RSS.
At doses of < or =60 mg/m(2), liposomal doxorubicin was well tolerated, with only mild hematological and nonhematological toxicity. All patients showed an objective measurable response, with 3 patients (20%) demonstrating a clinically complete response. There was a significant correlation between the duration of response and Avg Min T(90) > 44 degrees C (r(s) = 0.917, P < 0.0001) and the Mean[Tmin] (r(s) = 0.909, P < 0.0001). The RSS was significantly correlated with the interval between liposomal doxorubicin infusion and HT, as the smaller the time interval, the greater the clinical benefit (r = 0.76, P = 0.001).
The multimodal treatment was effective and well tolerated, producing an objective measurable response in all patients. Local HT had a significant effect on patients' response to the drug. The relationship between thermal dose and liposomal action requires further investigation.
本研究首次评估脂质体阿霉素（凯素；先灵葆雅制药公司）剂量≤60mg/km²，联合再程放疗及局部热疗治疗局部复发乳腺癌患者的耐受性和活性。
15例女性患者，曾在前胸壁行根治性乳房切除术及常规放疗（60Gy），进入一个多模式方案，包括初始放疗及每月输注脂质体阿霉素≤60mg/m²联合局部热疗。所有患者接受再程放疗，总剂量达30.6Gy（1.8Gy/分次，每周5天）。为评估药物安全性，前5例患者初始接受40mg/m²脂质体阿霉素剂量，随后增至60mg/m²。其他10例患者在所有6个化疗周期中均接受60mg/m²。使用频率为433MHz的波导在感兴趣区域（ROI）产生热疗。从代表每位患者ROI表面随时间变化的曲线中获得RSS，通过线性回归拟合。采用线性回归分析研究从脂质体阿霉素输注至热疗的时间间隔与RSS之间的关系。
在剂量≤60mg/m²时，脂质体阿霉素耐受性良好，仅出现轻度血液学和非血液学毒性。所有患者均表现出可客观测量的反应，3例患者（20%）出现临床完全缓解。反应持续时间与平均最低温度>44℃（rs = 0.917，P < 0.0001）及平均最低温度（rs = 0.909，P < 0.0001）之间存在显著相关性。RSS与脂质体阿霉素输注和热疗之间的时间间隔显著相关，时间间隔越短，临床获益越大（r = 0.76，P = 0.001）。
多模式治疗有效且耐受性良好，所有患者均产生可客观测量的反应。局部热疗对患者对药物的反应有显著影响。热剂量与脂质体作用之间的关系需要进一步研究。
