Zielinski Christoph C
Clinical Division of Oncology, Department of Medicine I, University Hospital, Central European Cooperative Oncology Group (CECOG), Vienna, Austria.
Oncology (Williston Park). 2003 Dec;17(12 Suppl 14):36-40.
In patients with advanced breast cancer, treatment with paclitaxel and doxorubicin has been shown to produce impressive overall response rates (up to 94%) and to prolong overall survival significantly over a combination of fluorouracil (5-FU), doxorubicin, and cyclophosphamide (Cytoxan, Neosar) in one prospective phase III clinical study. These results have been challenged, however, by other data demonstrating no survival advantage for taxane-based therapies. In addition, the combination of paclitaxel and doxorubicin has repeatedly been shown to be complicated by the development of treatment-related congestive heart failure, when cumulative doxorubicin doses exceed 300-360 mg/m2. Consequently, attempts have been made to increase the complete remission rate and overall survival resulting from first-line treatment of metastatic breast cancer without compromising patient safety. Gemcitabine (Gemzar)--a relatively effective, well-tolerated and partially non-cross-resistant antitumor compound with limited toxicity--represents an attractive alternative to paclitaxel/anthracycline combinations. Initial studies of combination therapy with gemcitabine and paclitaxel have produced an average response rate of 52%, with time to progression ranging between 7.0 and 14.5 months. Three-drug regimens containing gemcitabine, an anthracycline, and paclitaxel have been tested in phase II studies and have produced impressive response rates of 82.9% with gemcitabine, doxorubicin, and paclitaxel and 92% with gemcitabine, epirubicin (Ellence), and paclitaxel (GET). The Central European Cooperative Oncology Group has evaluated the GET regimen vs a regimen containing 5-FU, epirubicin, and cyclophosphamide (FEC) in a randomized, prospective phase III study. Interim toxicity analysis showed that the GET regimen was well tolerated but produced more grade 4 neutropenia (64% vs 42%, P = .084) and significantly more grade 4 thrombocytopenia (12% vs 0%; P < .001) than FEC. Anaphylactic/allergic reactions, peripheral polyneuropathy, nausea, and cardiotoxicity constituted rare events and did not exceed grade 1 or 2 in severity. Although final data from this phase III trial are not yet available, preliminary analysis suggests the GET regimen represents an attractive option for patients with advanced breast cancer.
在晚期乳腺癌患者中，一项前瞻性III期临床研究表明，与氟尿嘧啶（5-FU）、阿霉素和环磷酰胺（环磷酰胺、异环磷酰胺）联合使用相比，紫杉醇和阿霉素治疗可产生令人印象深刻的总体缓解率（高达94%），并显著延长总生存期。然而，其他数据对这些结果提出了质疑，这些数据表明基于紫杉烷的疗法没有生存优势。此外，当阿霉素累积剂量超过300-360mg/m²时，紫杉醇和阿霉素联合使用反复被证明会因治疗相关的充血性心力衰竭的发生而变得复杂。因此，人们试图在不影响患者安全的情况下提高转移性乳腺癌一线治疗的完全缓解率和总生存期。吉西他滨（健择）——一种相对有效、耐受性良好且部分无交叉耐药性的抗肿瘤化合物，毒性有限——是紫杉醇/蒽环类药物联合使用的一种有吸引力的替代方案。吉西他滨和紫杉醇联合治疗的初步研究产生了52%的平均缓解率，进展时间在7.0至14.5个月之间。含有吉西他滨、一种蒽环类药物和紫杉醇的三药方案已在II期研究中进行了测试，吉西他滨、阿霉素和紫杉醇的缓解率为82.9%，吉西他滨、表柔比星（表阿霉素）和紫杉醇（GET）的缓解率为92%。中欧合作肿瘤学组在一项随机、前瞻性III期研究中评估了GET方案与含有5-FU、表柔比星和环磷酰胺（FEC）的方案。中期毒性分析表明，GET方案耐受性良好，但与FEC相比产生了更多的4级中性粒细胞减少（64%对42%，P = 0.084）和显著更多的4级血小板减少（12%对0%；P < 0.001）。过敏/过敏反应、周围神经病变、恶心和心脏毒性构成罕见事件，严重程度不超过1级或2级。尽管这项III期试验的最终数据尚未获得，但初步分析表明，GET方案是晚期乳腺癌患者的一个有吸引力的选择。
