Ibrahim N K, Sahin A A, Dubrow R A, Lynch P M, Boehnke-Michaud L, Valero V, Buzdar A U, Hortobagyi G N
Department of Breast Medical Oncology, University of Texas M D Anderson Cancer Center, Houston 77030, USA.
Lancet. 2000 Jan 22;355(9200):281-3. doi: 10.1016/S0140-6736(99)06195-4.
Docetaxel and vinorelbine as combined treatment for metastatic breast cancer can have the dose-limiting toxic effects of mucositis and neutropenic fever. We report unexpected ischaemic colitis in six patients associated with docetaxel-based therapy, three of whom were treated in a phase I study designed to establish the maximum tolerated dose of this combination with the prophylactic use of granulocyte-colony-stimulating factor.
Between August, 1997, and December, 1998, 14 patients with metastatic breast cancer were treated with vinorelbine, docetaxel, and granulocyte-colony-stimulating factor in a phase I study. Three patients developed colitis similar to that seen in typhlitis. Three additional patients were identified during scheduled review of toxic effects in patients participating in clinical trials involving docetaxel.
Three patients on combined vinorelbine and docetaxel developed colitis-like symptoms. Two patients died, one from necrotic bowel and the other from neutropenic fever and colitis. Two of the patients presented on day 7 and day 8 of chemotherapy, respectively, with neutropenic fever and abdominal pain; the third patient developed neutropenia without fever and abdominal pain on day 8. The other three patients were treated with docetaxel, docetaxel and pamidronate disodium, or docetaxel and cyclophosphamide. All three patients presented with abdominal pain on days 10, 5, and 4, respectively. One had non-neutropenic fever, another had neutropenic fever, and the third was afebrile and non-neutropenic at the time of presentation with abdominal pain. Three patients had blood in their diarrhoea, abdominal tenderness, or both. Computed tomography of the abdomen and pelvis showed features of colitis in three patients.
This serious complication may result from the use of docetaxel and may be exacerbated by its combination with vinorelbine. Study of hospital-based patients treated with taxane-based chemotherapy is underway to find out the frequency of such complications.
多西他赛和长春瑞滨联合用于治疗转移性乳腺癌时,可能会产生黏膜炎和中性粒细胞减少性发热等剂量限制性毒性作用。我们报告了6例与多西他赛为基础的治疗相关的意外缺血性结肠炎病例,其中3例患者是在一项旨在确定该联合用药最大耐受剂量并预防性使用粒细胞集落刺激因子的I期研究中接受治疗的。
在1997年8月至1998年12月期间,14例转移性乳腺癌患者在一项I期研究中接受了长春瑞滨、多西他赛和粒细胞集落刺激因子治疗。3例患者发生了类似于盲肠炎的结肠炎。在对参与多西他赛相关临床试验患者的毒性反应进行定期复查时,又发现了另外3例患者。
3例接受长春瑞滨和多西他赛联合治疗的患者出现了结肠炎样症状。2例患者死亡,1例死于坏死性肠病,另1例死于中性粒细胞减少性发热和结肠炎。其中2例患者分别在化疗第7天和第8天出现中性粒细胞减少性发热和腹痛;第3例患者在第8天出现无发热和腹痛的中性粒细胞减少。另外3例患者分别接受了多西他赛、多西他赛与帕米膦酸二钠联合治疗或多西他赛与环磷酰胺联合治疗。这3例患者分别在第10天(1例)、第5天(1例)和第4天(1例)出现腹痛。1例有非中性粒细胞减少性发热,另1例有中性粒细胞减少性发热,第3例在出现腹痛时无发热且非中性粒细胞减少。3例患者腹泻带血、腹部压痛或两者皆有。腹部和盆腔计算机断层扫描显示3例患者有结肠炎特征。
这种严重并发症可能是使用多西他赛所致,并且其与长春瑞滨联合使用可能会使其加重。正在对接受紫杉烷类化疗的住院患者进行研究,以查明此类并发症的发生率。