O'Day S J, Gammon G, Boasberg P D, Martin M A, Kristedja T S, Guo M, Stern S, Edwards S, Fournier P, Weisberg M, Cannon M, Fawzy N W, Johnson T D, Essner R, Foshag L J, Morton D L
Division of Medical and Surgical Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA. o'
J Clin Oncol. 1999 Sep;17(9):2752-61. doi: 10.1200/JCO.1999.17.9.2752.
Concurrent biochemotherapy results in high response rates but also significant toxicity in patients with metastatic melanoma. We attempted to improve its efficacy and decrease its toxicity by using decrescendo dosing of interleukin-2 (IL-2), posttreatment granulocyte colony-stimulating factor (G-CSF), and low-dose tamoxifen.
Forty-five patients with poor prognosis metastatic melanoma were treated at a community hospital inpatient oncology unit affiliated with the John Wayne Cancer Institute (Santa Monica, CA) between July 1995 and September 1997. A 5-day modified concurrent biochemotherapy regimen of dacarbazine, vinblastine, cisplatin, decrescendo IL-2, interferon alfa-2b, and tamoxifen was repeated at 21-day intervals. G-CSF was administered beginning on day 6 for 7 to 10 days.
The overall response rate was 57% (95% confidence interval, 42% to 72%), the complete response rate was 23%, and the partial response rate was 34%. Complete remissions were achieved in an additional 11% of patients by surgical resection of residual disease after biochemotherapy. The median time to progression was 6.3 months and the median duration of survival was 11.4 months. At a maximum follow-up of 36 months (range, 10 to 36 months), 32% of patients are alive and 14% remain free of disease. Decrescendo IL-2 dosing and administration of G-CSF seemed to reduce toxicity, length of hospital stay, and readmission rates. No patient required intensive care unit monitoring, and there were no treatment-related deaths.
The data from this study indicate that the modified concurrent biochemotherapy regimen reduces the toxicity of concurrent biochemotherapy with no apparent decrease in response rate in patients with poor prognosis metastatic melanoma.
同步生物化疗可使转移性黑色素瘤患者获得较高的缓解率,但也会产生显著的毒性。我们尝试通过采用递减剂量的白细胞介素-2(IL-2)、治疗后使用粒细胞集落刺激因子(G-CSF)以及低剂量他莫昔芬来提高其疗效并降低毒性。
1995年7月至1997年9月期间,在加利福尼亚州圣莫尼卡市约翰·韦恩癌症研究所附属的一家社区医院住院肿瘤科,对45例预后不良的转移性黑色素瘤患者进行了治疗。采用达卡巴嗪、长春碱、顺铂、递减剂量的IL-2、干扰素α-2b和他莫昔芬的5天改良同步生物化疗方案,每21天重复一次。从第6天开始给予G-CSF,持续7至10天。
总缓解率为57%(95%置信区间,42%至72%),完全缓解率为23%,部分缓解率为34%。通过生物化疗后对残留病灶进行手术切除,另外11%的患者实现了完全缓解。疾病进展的中位时间为6.3个月,中位生存期为11.4个月。在最长36个月(范围为10至36个月)的随访中,32%的患者存活,14%的患者无疾病复发。递减剂量的IL-2给药和G-CSF的使用似乎降低了毒性、缩短了住院时间并降低了再入院率。没有患者需要重症监护病房监测,也没有与治疗相关的死亡病例。
本研究数据表明,改良同步生物化疗方案降低了同步生物化疗的毒性,且在预后不良的转移性黑色素瘤患者中缓解率没有明显下降。