Planting A S, van der Burg M E, de Boer-Dennert M, Stoter G, Verweij J
Department of Medical Oncology, Rotterdam Cancer Institute/Daniel den Hoed Kliniek, The Netherlands.
Ann Oncol. 1995 Feb;6(2):190-2. doi: 10.1093/oxfordjournals.annonc.a059117.
In a previous phase I study we showed that single-agent cisplatin can be given weekly for six weeks at a dose of 80 mg/m2/wk. It has been suggested that etoposide has synergistic activity with cisplatin and the drug can be given orally continuously. We therefore performed a phase I study with weekly cisplatin combined with oral etoposide.
Nineteen patients with metastases of a solid tumor were entered in the study. Cisplatin was administered in hypertonic saline (NaCl 3%). Etoposide was administered as 50-mg capsules.
The starting dose was cisplatin weekly at a dose of 70 mg/m2 for six weeks combined with daily oral etoposide at a dose of 50 mg. At the maximum tolerable dose of cisplatin 75 mg/m2/wk and etoposide 50 mg/m2 daily, leukocytopenia and thrombocytopenia were dose-limiting toxic effects which resulted in frequent treatment delays. Other toxicities were mild. Finally, a dose of cisplatin 70 mg/m2/wk weeks 1-2-3 and weeks 5-6-7 in combination with etoposide 50 mg orally days 1-15 and days 29-43 combined a high median cisplatin dose intensity of 52.5 mg/m2/wk with a good patient tolerance.
It is feasible to administer frequently dosed cisplatin in combination with oral etoposide. Leukocytopenia and thrombocytopenia are dose-limiting toxicities. The schedule will be explored further in phase II studies.
在之前的一项I期研究中，我们发现单药顺铂可以每周给药一次，持续六周，剂量为80mg/m²/周。有研究表明依托泊苷与顺铂具有协同活性，且该药物可以连续口服给药。因此，我们开展了一项I期研究，将每周一次的顺铂与口服依托泊苷联合应用。
19例实体瘤转移患者纳入本研究。顺铂通过高渗盐水（3%氯化钠）给药。依托泊苷以50mg胶囊形式给药。
起始剂量为顺铂每周70mg/m²，共六周，联合每日口服依托泊苷50mg。在顺铂最大耐受剂量为75mg/m²/周、依托泊苷每日50mg/m²时，白细胞减少和血小板减少成为剂量限制性毒性反应，导致频繁的治疗延迟。其他毒性反应较轻。最终，顺铂剂量为第1 - 2 - 3周和第5 - 6 - 7周70mg/m²/周，联合依托泊苷在第1 - 15天和第29 - 43天口服50mg，该方案结合了52.5mg/m²/周的高中位顺铂剂量强度和良好的患者耐受性。
频繁给药的顺铂联合口服依托泊苷是可行的。白细胞减少和血小板减少是剂量限制性毒性反应。该方案将在II期研究中进一步探索。
