Rose P G, Blessing J A, Van Le L, Waggoner S
Department of Obstetrics and Gynecology, University Hospitals of Cleveland, Cleveland, Ohio, 44106, USA.
Gynecol Oncol. 1998 Aug;70(2):263-6. doi: 10.1006/gyno.1998.5097.
Previous studies by the Gynecologic Oncology Group have demonstrated no activity with bolus etoposide in squamous cell carcinoma of the cervix. Prolonged oral etoposide, which exploits the schedule dependency of this agent, has demonstrated activity in non-small cell carcinoma of the lung and has been studied in combination therapy with cisplatin. To evaluate prolonged oral etoposide in previously treated squamous cell carcinoma of the cervix, the current Phase II trial was conducted.
Eligibility included squamous cell cancer of the cervix, measurable disease, allowed no more than one prior chemotherapy regimen which did not include etoposide, WBC >/=3000/microliter, platelet count >/=100, 000/microliter, serum creatinine </=2 mg%, and adequate hepatic function. The starting dose was 50 mg/m2/day (40 mg/m2/day for prior radiotherapy) as a single daily dose for 21 days, every 28 days. Based on toxicity, a dose escalation to a maximum dose of 60 mg/m2/day was prescribed.
Twenty-five patients were entered on this study; 24 were evaluable for toxicity. A median of 2 courses was given (range 1-8). All but one had received radiation therapy and 20 had received prior chemotherapy. Oral etoposide was not well tolerated with grade 4 neutropenia occurring in 33.3% and grade 4 thrombocytopenia occurring in 15%. Seven patients were unable to complete their first cycle due to toxicity and 8 patients received only one course of therapy. Of the remaining patients, 6 required dose reductions to 30 mg/m2/day. Only 3 patients were able to be dose-escalated to 50 mg/m2/day. Seventeen patients completed one course of therapy and were evaluable for response, of whom 16 had received prior radiotherapy and 15 prior chemotherapy. Two responses (11.8%) were observed, one complete response and one partial response. Both of these patients had disease in nonirradiated sites and one was chemotherapy-naive. Based on an intent-to-treat analysis, the response rate was 8.3%.
Prior radiation therapy limited the ability to deliver prolonged oral etoposide. At the maximum tolerated dose, this regimen is not significantly active as second-line chemotherapy in squamous cell carcinoma of the cervix.
妇科肿瘤学组先前的研究表明，大剂量静脉注射依托泊苷对子宫颈鳞状细胞癌无活性。延长口服依托泊苷可利用该药物的时间依赖性，已证明其对非小细胞肺癌有活性，并已在与顺铂的联合治疗中进行了研究。为了评估延长口服依托泊苷在先前治疗的子宫颈鳞状细胞癌中的疗效，开展了当前的II期试验。
入选标准包括子宫颈鳞状细胞癌、可测量的疾病、允许不超过一种不包括依托泊苷的先前化疗方案、白细胞计数≥3000/微升、血小板计数≥100,000/微升、血清肌酐≤2mg%以及肝功能正常。起始剂量为50mg/m²/天（先前接受过放疗的患者为40mg/m²/天），每日单次给药，共21天，每28天为一个周期。根据毒性情况，可将剂量增至最大60mg/m²/天。
25例患者进入本研究；24例可评估毒性。中位给药疗程为2个疗程（范围1 - 8个疗程）。除1例患者外，所有患者均接受过放疗，20例接受过先前的化疗。口服依托泊苷耐受性不佳，4级中性粒细胞减少症发生率为33.3%，4级血小板减少症发生率为15%。7例患者因毒性无法完成第一个周期，8例患者仅接受了一个疗程的治疗。其余患者中，6例需要将剂量减至30mg/m²/天。只有3例患者能够将剂量增至50mg/m²/天。17例患者完成了一个疗程的治疗并可评估疗效，其中16例接受过先前的放疗，15例接受过先前的化疗。观察到2例缓解（11.8%），1例完全缓解和1例部分缓解。这2例患者的疾病均位于未接受放疗的部位，其中1例未接受过化疗。基于意向性分析，缓解率为8.3%。
先前的放疗限制了延长口服依托泊苷的给药能力。在最大耐受剂量下该方案作为子宫颈鳞状细胞癌的二线化疗方案活性不显著。
