Morabito Alessandro, Gattuso Domenico, Stani Simonetta Chiara, Fanelli Massimo, Ferraù Francesco, De Sio Livia, Castellana Maria Angela, Lorusso Vito, Priolo Domenico, Vitale Stefano, Sarmiento Roberta, Lo Vullo Salvatore, Mariani Luigi, Gasparini Giampietro
Division of Medical Oncology, San Filippo Neri Hospital, Rome, Italy.
Breast Cancer Res Treat. 2004 Aug;86(3):249-57. doi: 10.1023/B:BREA.0000036898.45123.e9.
The present study was designed with the aim of evaluating the tolerability and activity of pegylated liposomial doxorubicin (PLD) in combination with weekly docetaxel as first line treatment of advanced breast cancer.
Fifty-seven patients entered the study. PLD was administered at escalating doses starting from 30 mg/m2, on day 1; docetaxel was administered at the fixed dose of 35 mg/m2 on days 2 and 9. A cycle of therapy consisted of 21 days.
The MTD was achieved at the dose of 40 mg/m2 of PLD, being febrile neutropenia and palmar-plantar-erythrodisesthesia (PPE) the dose-limiting toxicities (DLTs), so that the fixed dose of PLD for the Phase II study was 35 mg/m2. Forty-two consecutive patients received treatment at the established dose for a total of 194 cycles: among these, three patients were withdrawn for severe allergic reaction at the first administration of PLD. Hematological toxicity was moderate, the most common grade 1-3 non-hematological toxicities were stomatitis and PPE, occurring in 20 (47.5%) and 16 (38%) patients, respectively. No cardiac toxicity was recorded. According to the intent to treat analysis a major objective response was observed in 59.5% of patients (95% CI, 43.3-74.4%), with a median time to progression of 9 months and an estimated overall survival at 18 months of 62%.
The combination of PLD and weekly docetaxel is an effective first-line therapy for patients with advanced breast cancer. PPE and mucositis are the most relevant side effects of such a combination.
本研究旨在评估聚乙二醇化脂质体阿霉素（PLD）联合多西他赛每周给药作为晚期乳腺癌一线治疗的耐受性和活性。
57例患者进入本研究。PLD于第1天开始以30mg/m²的剂量递增给药；多西他赛于第2天和第9天以35mg/m²的固定剂量给药。一个治疗周期为21天。
PLD剂量为40mg/m²时达到最大耐受剂量（MTD），发热性中性粒细胞减少和手足红斑感觉异常（PPE）为剂量限制性毒性（DLT），因此II期研究中PLD的固定剂量为35mg/m²。42例连续患者按既定剂量接受治疗，共194个周期：其中3例患者在首次给予PLD时因严重过敏反应退出。血液学毒性为中度，最常见的1-3级非血液学毒性为口腔炎和PPE，分别发生在20例（47.5%）和16例（38%）患者中。未记录到心脏毒性。根据意向性分析，59.5%的患者观察到主要客观缓解（95%CI，43.3-74.4%），中位疾病进展时间为9个月，18个月时的估计总生存率为62%。
PLD联合多西他赛每周给药是晚期乳腺癌患者有效的一线治疗方案。PPE和粘膜炎是该联合方案最相关的副作用。
