Planting A S, de Mulder P H, de Graeff A, Verweij J
Department of Medical Oncology, Rotterdam Cancer Institute/Daniel den Hoed Kliniek, The Netherlands.
Eur J Cancer. 1997 Jan;33(1):61-5. doi: 10.1016/s0959-8049(96)00311-5.
In a phase I study of weekly administered cisplatin, we observed a major response in 8 of 9 patients with locally far advanced head and neck cancer. Therefore, a phase II study was initiated to explore the activity and tolerance of this weekly cisplatin regimen. 59 patients with locally advanced head and neck cancer were entered into this phase II study. Cisplatin was administered at a dose of 80 mg/m2 weekly for 6 cycles. Cisplatin was administered in hypertonic saline (3% NaCl) as a 3-h infusion with standard pre- and posthydration. 51 patients were evaluable for response and 55 for toxicity. Only 9 patients were able to complete the treatment with the planned dose intensity of 80 mg/m2/week. Complete disappearance of the tumour was observed in 8 patients and a partial response in 22 (response rate 59%; 51% of all eligible patients 95% CI limits 37-63%). Stable disease was observed in 12 patients, and the tumour progressed in 9 patients. 47 patients subsequently received high-dose radiotherapy, 1 radiotherapy and surgery and 4 patients second-line chemotherapy. The median progression-free survival and median overall survival for all patients were 32 weeks and 56 weeks, respectively. Haematological toxicity consisted of anaemia, leucocytopenia (grade 3 + 4 in 17 patients) and thrombocytopenia (grade 3 + 4 in 17 patients). Because of leuco- and/or thrombocytopenia, treatment was delayed in 30 patients while 13 were taken off the study because of delayed bone marrow recovery. Non-haematological toxicities were: ototoxicity grade 1 in 3 patients, grade 2 in 7 and grade 3 in 3 patients; nephrotoxicity grade 1 in 13 patients, grade 2 in 2 and grade 3 in 1 patient. Neurotoxicity grade 1 was observed in only 8 patients. Cisplatin, as a single agent, administered at high-dose intensity, has an antitumour activity comparable with that of combination regimens in locally advanced head and neck cancer. The pattern of toxicity is different: leuco- and thrombocytopenia jeopardize the dose intensity concept; for patients ototoxicity is the more relevant toxicity. Further studies with weekly cisplatin are of interest particularly with newer measures to reduce toxicity.
在一项关于每周给药顺铂的I期研究中，我们观察到9例局部晚期头颈癌患者中有8例出现主要缓解。因此，启动了一项II期研究，以探索这种每周顺铂方案的活性和耐受性。59例局部晚期头颈癌患者进入了这项II期研究。顺铂以80mg/m²的剂量每周给药，共6个周期。顺铂在高渗盐水中（3%氯化钠）以3小时输注的方式给药，并进行标准的水化预处理和后处理。51例患者可评估疗效，55例可评估毒性。只有9例患者能够按照计划的剂量强度80mg/m²/周完成治疗。8例患者肿瘤完全消失，22例部分缓解（缓解率59%；所有符合条件患者的51%，95%置信区间为37 - 63%）。12例患者疾病稳定，9例患者肿瘤进展。47例患者随后接受了高剂量放疗，1例接受了放疗和手术，4例接受了二线化疗。所有患者的无进展生存期和总生存期的中位数分别为32周和56周。血液学毒性包括贫血、白细胞减少（17例3/4级）和血小板减少（17例3/4级）。由于白细胞和/或血小板减少，30例患者治疗延迟，13例因骨髓恢复延迟而退出研究。非血液学毒性为：3例患者出现1级耳毒性，7例2级，3例3级；13例患者出现1级肾毒性，2例2级，1例3级。仅8例患者观察到1级神经毒性。顺铂作为单一药物，以高剂量强度给药，在局部晚期头颈癌中的抗肿瘤活性与联合方案相当。毒性模式不同：白细胞和血小板减少危及剂量强度概念；对患者来说，耳毒性是更相关的毒性。每周使用顺铂进行进一步研究很有意义，特别是采用新的措施来降低毒性。
