Edmonson J H, McCormack G M, Wieand H S, Kugler J W, Krook J E, Stanhope C R, Everson L K, Laurie J A, Ebbert L P, Malkasian G D
Mayo Clinic, Rochester, MN 55905.
J Natl Cancer Inst. 1989 Oct 4;81(19):1500-4. doi: 10.1093/jnci/81.19.1500.
Between March 1985 and January 1987, 103 women with histologically proven stage III-IV ovarian carcinoma were randomly allocated to groups receiving monthly intravenous regimens of 1 g of cyclophosphamide/m2 plus either 60 mg of cisplatin (CDDP)/m2 or 150 mg of carboplatin (CBDCA)/m2 for 1 year unless disease progressed earlier. The groups were well balanced according to the stratification factors (age, histologic differentiation, extent of residual disease, and performance score), and both treatments were well tolerated and produced similar median first-course leukopenia (2,200 and 2,000 cells/microL) and thrombocytopenia (220,000 and 202,500 cells/microL). The CBDCA regimen was less emetogenic. After an interim analysis in January 1987 revealed superior progression-free survival for the group of 53 patients receiving CDDP (P = .005), the study was closed to further accrual. Those 24 patients still receiving CBDCA were encouraged to cross over to the CDDP-based regimen and 21 of them did. Following treatment crossover, the relative risk of death associated with original allocation to CBDCA receded from 1.79 to 0.97, indicating success of the salvage treatment using the CDDP-based regimen. This aborted study demonstrated the superiority of CDDP over CBDCA when the two platinum compounds were compared at equally myelosuppressive low doses in combination with 1 g of cyclophosphamide/m2. If CDDP is to be supplanted by CBDCA, larger, more myelosuppressive doses of CBDCA will be required. The platinum drug antitumor effect is a critically important therapeutic feature of this combination.
1985年3月至1987年1月期间，103名经组织学证实为III-IV期卵巢癌的女性被随机分配至接受每月静脉注射方案的组中，方案为每平方米体表面积1克环磷酰胺加60毫克顺铂（CDDP）/平方米或150毫克卡铂（CBDCA）/平方米，持续1年，除非疾病提前进展。根据分层因素（年龄、组织学分化、残留疾病范围和体能评分），两组情况良好平衡，两种治疗耐受性均良好，且产生相似的中位首次疗程白细胞减少症（每微升2200和2000个细胞）和血小板减少症（每微升220000和202500个细胞）。CBDCA方案的致吐性较小。1987年1月的中期分析显示，接受CDDP的53名患者组的无进展生存期更优（P = 0.005），该研究停止进一步入组。鼓励仍在接受CBDCA治疗的24名患者转用基于CDDP的方案，其中21名患者照做。治疗方案转换后，与最初分配接受CBDCA相关的死亡相对风险从1.79降至0.97，表明使用基于CDDP的方案进行挽救治疗取得成功。这项中止的研究表明，当两种铂类化合物在同等骨髓抑制低剂量下与每平方米体表面积1克环磷酰胺联合使用时，CDDP优于CBDCA。如果要用CBDCA取代CDDP，则需要更大剂量、骨髓抑制作用更强的CBDCA。铂类药物的抗肿瘤作用是这种联合治疗的一个极其重要的治疗特性。
