Foppoli M, Citterio G, Polastri D, Guerrieri R
Divisione di Medicina II, IRCCS H S. Raffaele, Milan, Italy.
Tumori. 1995 Mar-Apr;81(2):102-6. doi: 10.1177/030089169508100206.
A Phase I study of repetitive courses of chemotherapy (carmustine, cis-platinum, dacarbazine) and immunotherapy (continuous intravenous infusion recombinant interleukin-2 (rIL-2) and subcutaneous (sc) alpha-interferon 2b) plus tamoxifen was performed in order to establish a more efficacious way to sequence this kind of treatment for advanced malignant melanoma.
Patients who had measurable metastatic melanoma, a Karnofsky performance status > or = 80, and no clinically significant hematologic or cardiac disfunction were considered eligible. Treatment consisted of BCNU, 150 mg/m2 i.v. day 1 in alternating cycles; DTIC, 220 mg/m2 i.v. days 1, 2 and 3; CDDP, 25 mg/m2 i.v. days 1, 2 and 3; tamoxifen 10 mg twice/day per os continuously; rIL-2, 18 x 10(6) IU/m2/day continuous i.v. infusion days 5-8 (96 h) and days 19-22 (96 h); alpha-interferon (IFN) s.c. 3 x 10(6) U day 12, 6 x 10(6) U day 14, 9 x 10(6) U days 16, 19, 21, 23, 26, and 28 (from cycle 2, 9 x 10(6) U days 2, 5, 7, 9, 12, 14, 16, 19, 21, 23, 26, and 28). Two consecutive cycles were planned until response evaluation.
Three patients were treated according with the protocol; none of them was able to respect the planned dose-intensity schedule. The given dose intensity/planned dose intensity ratios were as follows: DTIC, 0.74 (range, 0.70-0.80); CDDP, 0.77 (0.72-0.80); BCNU, 0.77 (0.72-0.80); rIL-2, 0.65 (0.36-0.80); alpha-IFN, 0.01 (0-0.03); tamoxifen, 1.0. Systemic side effects of rIL-2 and myelotoxicity were the main reasons for treatment delay and/or dose-reduction, and for the long period of hospital care.
We conclude that the treatment schedule is not feasible. However, since we believe that combined chemo-immunotherapy is a potentially active treatment in metastatic malignant melanoma, we have modified it in order to make it more feasible and consequently efficacious.
开展了一项关于重复化疗疗程（卡莫司汀、顺铂、达卡巴嗪）和免疫疗法（持续静脉输注重组白细胞介素-2（rIL-2）及皮下注射α-干扰素2b）加他莫昔芬的I期研究，以确立一种对晚期恶性黑色素瘤进行此类治疗的更有效序贯方法。
有可测量转移性黑色素瘤、卡氏评分≥80且无临床显著血液学或心脏功能障碍的患者被视为合格。治疗方案包括：卡莫司汀，150mg/m²静脉注射，第1天，交替周期使用；达卡巴嗪，220mg/m²静脉注射，第1、2和3天；顺铂，25mg/m²静脉注射，第1、2和3天；他莫昔芬，10mg，每日口服两次，持续服用；rIL-2，18×10⁶IU/m²/天，第5 - 8天（96小时）和第19 - 22天（96小时）持续静脉输注；α-干扰素皮下注射，第12天3×10⁶U，第14天6×10⁶U，第16、19、21、23、26和28天9×10⁶U（从第2周期起，第2、5、7、9、12、14、16、19、21、23、26和28天9×10⁶U）。计划进行两个连续周期直至疗效评估。
3例患者按方案接受治疗；但无一例能够遵循计划的剂量强度方案。实际给予剂量强度与计划剂量强度的比值如下：达卡巴嗪，0.74（范围0.70 - 0.80）；顺铂，0.77（0.72 - 0.80）；卡莫司汀，0.77（0.72 - 0.80）；rIL-2，0.65（0.36 - 0.80）；α-干扰素，0.01（0 - 0.03）；他莫昔芬，1.0。rIL-2的全身副作用和骨髓毒性是治疗延迟和/或剂量减少以及住院时间延长的主要原因。
我们得出结论，该治疗方案不可行。然而，由于我们认为联合化疗免疫疗法对转移性恶性黑色素瘤可能是一种有效的治疗方法，我们已对其进行修改，使其更可行且有效。
