Lamar R E, Greco F A, Johnson D H, Murphy P B, Hainsworth J D
Division of Medical Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Cancer. 1994 Apr 1;73(7):1842-8. doi: 10.1002/1097-0142(19940401)73:7<1842::aid-cncr2820730711>3.0.co;2-f.
The authors evaluated a high-intensity inpatient regimen using augmented but subtransplantation doses of multiple agents in patients with metastatic breast cancer. Two high-dose courses were given in an attempt to improve the efficacy of high-dose regimens using a single course.
Forty women received treatment between October 1988 and October 1991. The median age was 38 years (range, 24-56 years). Twenty-five patients were receiving their first chemotherapy for metastatic disease; 15 patients had received one or more prior regimens. The patients received two courses of chemotherapy, which consisted of the following: cyclophosphamide 1500 mg/m2 intravenously (i.v.) on days 1 and 2; doxorubicin 45 mg/m2 i.v. on days 1 and 2; cisplatin 20 mg/m2 i.v. on days 1, 2, 3, 8, 9, and 10; 5-fluorouracil 1000 mg/m2 on days 8, 9, and 10 (continuous infusion); methotrexate 100 mg/m2 i.v. on days 15 and 22; leucovorin 15 mg/m2 i.v. or by mouth for four doses beginning 24 hours after methotrexate. Etoposide 400 mg/m2 i.v. on days 1, 2, and 3 was substituted for doxorubicin in 14 patients who had received prior doxorubicin.
Twenty-nine of 40 patients (73%) had objective response to therapy, with 10 (25%) complete responses. Four patients who obtained a complete response remain disease-free at 14, 21, 28, and 32 months, respectively; all of these patients received this regimen as first-line therapy for metastatic disease. Myelosuppression was severe, with median durations of leukocytes less than 1000/microliters and platelets less than 50,000/microliters of 15 days (range, 7-48 days) and 13 days (range, 3-49 days), respectively. Moderate or severe mucositis occurred in 56 of 68 courses. Four patients (10%) had treatment-related deaths.
This regimen produced high overall response and complete response rates compared with standard regimens. However, only 15% of patients who received this therapy as first-line treatment for metastatic breast cancer remain disease-free, and median response duration was shorter than that reported using high-dose therapy with bone marrow support. Toxicity with this regimen was greater than anticipated, although myelosuppression and stomatitis would be reduced by the use of cytokines. This regimen does not improve results achieved with standard therapy sufficiently to justify its toxicity and expense.
作者评估了一种高强度住院治疗方案，该方案在转移性乳腺癌患者中使用增加剂量但低于移植剂量的多种药物。给予两个高剂量疗程，试图通过单疗程高剂量方案提高疗效。
1988年10月至1991年10月期间，40名女性接受了治疗。中位年龄为38岁（范围24 - 56岁）。25例患者因转移性疾病首次接受化疗；15例患者曾接受过一种或多种先前的治疗方案。患者接受两个疗程的化疗，具体如下：第1天和第2天静脉注射环磷酰胺1500mg/m²；第1天和第2天静脉注射阿霉素45mg/m²；第1、2、3、8、9和10天静脉注射顺铂20mg/m²；第8、9和10天持续静脉输注5-氟尿嘧啶1000mg/m²；第15天和第22天静脉注射甲氨蝶呤100mg/m²；在甲氨蝶呤后24小时开始，静脉注射或口服亚叶酸钙15mg/m²，共四剂。14例曾接受过阿霉素治疗的患者用第1、2和3天静脉注射依托泊苷400mg/m²替代阿霉素。
40例患者中有29例（73%）对治疗有客观反应，其中10例（25%）完全缓解。4例获得完全缓解的患者分别在14、21、28和32个月时仍无疾病；所有这些患者均接受该方案作为转移性疾病的一线治疗。骨髓抑制严重，白细胞中位数低于1000/微升和血小板低于50,000/微升的持续时间分别为15天（范围7 - 48天）和13天（范围3 - 49天）。68个疗程中有56个出现中度或重度粘膜炎。4例患者（10%）死于治疗相关原因。
与标准方案相比，该方案产生了较高的总体反应率和完全缓解率。然而，作为转移性乳腺癌一线治疗接受该疗法的患者中，只有15%仍无疾病，中位反应持续时间短于使用骨髓支持的高剂量疗法报告的时间。该方案的毒性大于预期，尽管使用细胞因子可减轻骨髓抑制和口腔炎。该方案未能充分改善标准治疗的结果，不足以证明其毒性和费用的合理性。
