Ito Y, Aiba K, Horikoshi N, Saotome T, Irie T, Sugiyama K, Nakane M, Hashimoto D, Yoshida N, Mizunuma N, Takahashi S, Tanigawara Y
Department of Medical Oncology, Cancer Institute Hospital, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
Int J Clin Oncol. 2001 Oct;6(5):242-7. doi: 10.1007/pl00012112.
Combination therapy with doxorubicin (DOX) and docetaxel (DOC), given 3 weeks apart, is one of the standard regimens used for treating metastatic breast cancer, but it frequently generates febrile neutropenia. To find a safer regimen with less myelotoxicity and the appropriate dose intensity, we conducted a phase I study of simultaneous weekly infusion with DOX and DOC.
Twenty-five patients with advanced breast cancer were treated with an intravenous push-injection of DOX that was immediately followed by a 1-h infusion of DOC. This was repeated every week for at least 6 weeks. The premedication employed was three 4-mg doses of dexamethasone every week. Patients were divided into four groups for which the doses of DOX and DOC were escalated in 5-mg/m2 increments.
In the 18 patients who were treated with DOX 15 or 20 mg/m2 and DOC 25 mg/m2, or lower, the regimen was found to be tolerable, without febrile episodes. The regimen with 20 mg/m2 of DOX and 30 mg/m2 of DOC was the maximum tolerated dose. Other indications of grade 3 toxicity included asthenia in 4% of patients, anorexia in 8%, and vomiting in 8%. Of the 25 patients, 14 had a partial response. The overall response rate was 56% (95% confidence interval [CI], 35% to 77%). The recommended dose for further trial was 20 mg/m2 of DOX and 25 mg/m2 of DOC.
Simultaneous weekly infusion with DOX and DOC was feasible, with modest neutropenia and preserved dose intensity. This regimen may be helpful in the management of patients with advanced breast cancer.
多柔比星（DOX）与多西他赛（DOC）间隔3周联合使用是治疗转移性乳腺癌的标准方案之一，但该方案常引发发热性中性粒细胞减少症。为找到一种骨髓毒性更低且剂量强度合适的更安全方案，我们开展了一项DOX与DOC每周同步输注的Ⅰ期研究。
25例晚期乳腺癌患者接受静脉推注DOX，随后立即进行1小时的DOC输注。每周重复此操作，至少持续6周。预处理采用每周3次、每次4毫克的地塞米松。患者分为四组，DOX和DOC的剂量以5毫克/平方米的增量递增。
在接受15或20毫克/平方米DOX和25毫克/平方米及以下DOC治疗的18例患者中，该方案耐受性良好，未出现发热情况。DOX 20毫克/平方米和DOC 30毫克/平方米的方案为最大耐受剂量。3级毒性的其他表现包括4%的患者出现乏力、8%的患者出现厌食、8%的患者出现呕吐。25例患者中，14例有部分缓解。总体缓解率为56%（95%置信区间[CI]，35%至77%）。进一步试验的推荐剂量为DOX 20毫克/平方米和DOC 25毫克/平方米。
DOX与DOC每周同步输注可行，中性粒细胞减少程度较轻且剂量强度得以维持。该方案可能有助于晚期乳腺癌患者的治疗。
