Hodi F Stephen, Soiffer Robert J, Clark Jeffrey, Finkelstein Dianne M, Haluska Frank G
Adult Oncology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Am J Clin Oncol. 2002 Jun;25(3):283-6. doi: 10.1097/00000421-200206000-00016.
Conventional chemotherapy in the treatment of malignant melanoma has been disappointingly ineffective. Although the most active single agent is dacarbazine, numerous trials support the activity of platinum analogs against melanoma. Several recent trials also demonstrate the single-agent activity of paclitaxel, and support the administration of these agents together in the treatment of a number of solid tumors. We conducted a phase II study treating patients with metastatic melanoma with paclitaxel as a 3-hour infusion of 175 mg/m2, and carboplatin dosed to yield an area under the curve of 7.5 administered during 30 minutes. Patients were previously untreated or treated once with a regimen not including a platinum or taxane agent and had a performance status of 0 or 1. Seventeen patients (8 males; 9 females; average age 51) were enrolled. Thirty-three percent of patients had disease involving the skin, 40% lungs, 33% lymph nodes, 26% liver, and 13% other visceral organs. Anaphylactic reactions developed in two patients associated with paclitaxel infusion, and the patients were subsequently taken off the study. Of the 15 remaining patients, 3 (20%) had partial responses, 7 (47%) had stable disease, and 5 (33%) showed evidence of progressive disease. Eleven patients experienced grade III or IV hematologic toxicity. All treatment-related toxicities were reversible. There were no treatment-related deaths. The combination of paclitaxel and carboplatin has moderate activity against malignant melanoma, with expected reversible hematologic toxicities. Although not prospectively compared with single agents, the combination of paclitaxel and carboplatin may be a treatment option for some patients. Comparisons with other treatment regimens and the search for additional active compounds against melanoma are needed.
传统化疗在恶性黑色素瘤的治疗中效果令人失望。虽然最有效的单一药物是达卡巴嗪,但大量试验证实铂类类似物对黑色素瘤也有活性。最近的一些试验还证明了紫杉醇的单药活性,并支持将这些药物联合用于多种实体瘤的治疗。我们进行了一项II期研究,用紫杉醇以175mg/m²的剂量静脉输注3小时,并给予卡铂,剂量为在30分钟内使曲线下面积达到7.5。患者之前未接受过治疗或仅接受过一次不包括铂类或紫杉烷类药物的治疗方案,且其体力状况评分为0或1。共纳入17例患者(8例男性;9例女性;平均年龄51岁)。33%的患者疾病累及皮肤,40%累及肺部,33%累及淋巴结,26%累及肝脏,13%累及其他内脏器官。两名患者在紫杉醇输注过程中出现过敏反应,随后退出研究。在其余15例患者中,3例(20%)有部分缓解,7例(47%)病情稳定,5例(33%)有疾病进展的证据。11例患者出现III级或IV级血液学毒性。所有与治疗相关的毒性均为可逆性。无治疗相关死亡。紫杉醇和卡铂联合方案对恶性黑色素瘤有中度活性,伴有预期的可逆性血液学毒性。虽然未与单一药物进行前瞻性比较,但紫杉醇和卡铂联合方案可能是一些患者的治疗选择。需要与其他治疗方案进行比较,并寻找更多对黑色素瘤有活性的化合物。