Crown J, Hakes T, Reichman B, Lebwohl D, Gilewski T, Surbone A, Currie V, Yao T J, Hudis C, Seidman A
Breast/Gynecologic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cancer. 1993 Feb 15;71(4):1254-7. doi: 10.1002/1097-0142(19930215)71:4<1254::aid-cncr2820710414>3.0.co;2-x.
High-dose chemotherapy with hematopoietic support produces high rates of response in metastatic breast cancer. To facilitate new high-dose regimens there is a need to identify active agents with toxicity limited to hematopoietic suppression. Cisplatin/etoposide is a highly active regimen in metastatic breast cancer, but cisplatin dose-escalation is limited by nonhematologic toxicity. Carboplatin is active in breast cancer and has marrow-dominant toxicity. Demonstration of activity for the combination of carboplatin and etoposide would facilitate their inclusion in high-dose programs.
A single treatment arm prospective Phase II study in patients with measurable or evaluable breast cancer was done.
Forty-six patients with metastatic breast cancer were treated with the combination of carboplatin and etoposide. Among 19 patients without prior chemotherapy, one complete and seven partial responses were observed, for an objective response rate of 42% (95% exact confidence intervals [CI], 20-67%). One partial response was seen among 12 patients with prior chemotherapy limited to the adjuvant setting. No responses were seen among 14 patients who had received prior chemotherapy for metastatic cancer. Two treatment-related deaths occurred, both attributable to sepsis. One patient returned to her community for treatment after receiving one course of protocol therapy before response assessment and could not be studied for response.
The activity observed with this regimen in patients with no prior chemotherapy coupled with its potential for dose escalation suggests a possible role in high-dose programs with hematopoietic support. The inactivity of the combination in patients with prior therapy for metastatic breast cancer indicates that there is no advantage to its use in the salvage setting.
高剂量化疗联合造血支持在转移性乳腺癌中产生较高的缓解率。为了推动新的高剂量方案，需要识别毒性仅限于造血抑制的活性药物。顺铂/依托泊苷是转移性乳腺癌中一种高度有效的方案，但顺铂剂量递增受到非血液学毒性的限制。卡铂在乳腺癌中具有活性，且毒性以骨髓为主。证明卡铂与依托泊苷联合用药的活性将有助于将其纳入高剂量方案。
对患有可测量或可评估乳腺癌的患者进行了单治疗组前瞻性II期研究。
46例转移性乳腺癌患者接受了卡铂与依托泊苷联合治疗。在19例未接受过化疗的患者中，观察到1例完全缓解和7例部分缓解，客观缓解率为42%（95%精确置信区间[CI]，20 - 67%）。在12例仅接受过辅助化疗的患者中观察到1例部分缓解。在14例接受过转移性癌化疗的患者中未观察到缓解。发生了2例与治疗相关的死亡，均归因于败血症。1例患者在接受一个疗程的方案治疗后，在缓解评估前返回社区治疗，无法对其缓解情况进行研究。
该方案在未接受过化疗的患者中观察到的活性及其剂量递增的潜力表明，在联合造血支持的高剂量方案中可能发挥作用。该联合方案在接受过转移性乳腺癌治疗的患者中无活性，表明在挽救治疗中使用该方案没有优势。
