Grunberg S M, Valentine J, Zackon I, Unger P
Vermont Cancer Center, University of Vermont, Burlington, USA.
Invest New Drugs. 1996;13(4):333-5. doi: 10.1007/BF00873140.
The combination of oral etoposide and oral cyclophosphamide is an active and easily administered outpatient regimen for non-small cell lung cancer with leukopenia as the most common severe toxicity. To maintain ease of outpatient administration and to take advantage of a differing dose-limiting toxicity, we attempted to add escalating doses of intravenous carboplatin to full-dose oral etoposide and oral cyclophosphamide for chemotherapy-naive patients with Stage IV non-small cell lung cancer. The first 4 patients received etoposide and cyclophosphamide (each at 50 mg PO BID Days 1-12 every 28 days) with intravenous carboplatin on Day 1 at a dose calculated by the Calvert formula to achieve AUC 4. With this regimen dose-limiting toxicity (2 patients with Grade 4 leukopenia/granulocytopenia) was noted. An additional 3 patients therefore received etoposide and cyclophosphamide at a 25% reduced dose (each at 50 mg PO BID Days 1-9 every 28 days) with intravenous carboplatin on Day 1 at a dose calculated to achieve AUC 4. Dose-limiting toxicity (2 patients with Grade 4 leukopenia/granulocytopenia) was again noted. One patient achieved a partial response maintained for 6 months. However potentiation of leukopenia/granulocytopenia by carboplatin prevents full-dose use of either cyclophosphamide and etoposide or of carboplatin in this regimen.
口服依托泊苷与口服环磷酰胺联合使用，是一种用于非小细胞肺癌的有效且易于管理的门诊治疗方案，其中白细胞减少是最常见的严重毒性反应。为了保持门诊给药的便利性，并利用不同的剂量限制性毒性，我们尝试将递增剂量的静脉注射卡铂添加到全剂量口服依托泊苷和口服环磷酰胺中，用于初治的IV期非小细胞肺癌患者。前4例患者接受依托泊苷和环磷酰胺（均为50mg口服，每日2次，第1 - 12天，每28天重复），第1天静脉注射卡铂，剂量根据卡尔弗特公式计算以达到AUC 4。采用该方案时，观察到剂量限制性毒性（2例4级白细胞减少/粒细胞减少）。因此，另外3例患者接受剂量降低25%的依托泊苷和环磷酰胺（均为50mg口服，每日2次，第1 - 9天，每28天重复），第1天静脉注射卡铂，剂量计算为达到AUC 4。再次观察到剂量限制性毒性（2例4级白细胞减少/粒细胞减少）。1例患者达到部分缓解并维持6个月。然而，在该方案中，卡铂增强白细胞减少/粒细胞减少的作用使得环磷酰胺、依托泊苷或卡铂均无法使用全剂量。
