Farker K, Merkel U, Wedding U, Hippius M, Höffken K, Hoffmann A
Institute of Clinical Pharmacology, Friedrich Schiller University Jena, Dornburger Strasse 159, 07740 Jena, Germany.
Int J Clin Pharmacol Ther. 2006 Jan;44(1):31-7. doi: 10.5414/cpp44031.
Several clinical trials have demonstrated that oxaliplatin is a useful agent in combination with 5-fluorouracil (5-FU) and folinic acid (FA) for the treatment of patients with colorectal carcinoma. The aims of this pilot study were to evaluate non-hematological toxicity and patient characteristics in gastrointestinal cancer patients treated with chronomodulated chemotherapy consisting of oxaliplatin, 5-FU and sodium folinate.
Patients with metastatic gastrointestinal cancer received a chronomodulated regimen with oxaliplatin (25 mg/m2), 5-FU (750 mg/m2) and sodium folinate (150 mg/m2). Non-hematological toxicities were evaluated and analyzed in relation to patient characteristics, i.e. age, sex, body weight, body mass index (BMI), body surface area and smoking status. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria.
The severity of non-hematological toxicity was generally moderate. Grade 4 toxicity was only found in 2 patients with diarrhea (12.5%). The most frequent common adverse events were nausea, Grades 1 - 2 in 13 patients (81.3%), followed by motor neuropathy, Grades 1 - 3 in 11 patients (68.9%). The analyses showed that patient characteristics such as BMI and smoking status were associated with mucositis/stomatitis, vomiting or mood alteration. Furthermore, there was a relationship between smoking status and the overall non-hematological toxicity. Smokers had significantly higher overall toxicity than non-smokers and body mass index correlated significant with overall toxicity.
The results of this pilot investigation suggest that a chronomodulated regimen with oxaliplatin, 5-FU and sodium folinate has a manageable non-hematological toxicity profile and that toxicity of the chronomodulated schedule studied depends on the patient characteristics. In further investigations, risk factors determining chemotherapeutic toxicity should be considered. Because of the small number of patients in this pilot investigation, the findings need to be confirmed in a larger clinical study.
多项临床试验已证明，奥沙利铂与5-氟尿嘧啶（5-FU）和亚叶酸（FA）联合使用是治疗结直肠癌患者的有效药物。本初步研究的目的是评估接受由奥沙利铂、5-FU和亚叶酸钙组成的时辰化疗的胃肠道癌患者的非血液学毒性和患者特征。
转移性胃肠道癌患者接受含奥沙利铂（25 mg/m²）、5-FU（750 mg/m²）和亚叶酸钙（150 mg/m²）的时辰化疗方案。根据患者特征，即年龄、性别、体重、体重指数（BMI）、体表面积和吸烟状况，对非血液学毒性进行评估和分析。毒性根据美国国立癌症研究所通用毒性标准分级。
非血液学毒性的严重程度一般为中度。仅在2例腹泻患者中发现4级毒性（12.5%）。最常见的不良事件是恶心，13例患者为1-2级（81.3%），其次是运动神经病变，11例患者为1-3级（68.9%）。分析表明，BMI和吸烟状况等患者特征与粘膜炎/口腔炎、呕吐或情绪改变有关。此外，吸烟状况与总体非血液学毒性之间存在关联。吸烟者的总体毒性明显高于非吸烟者，体重指数与总体毒性显著相关。
本初步研究结果表明，含奥沙利铂、5-FU和亚叶酸钙的时辰化疗方案具有可控的非血液学毒性特征，且所研究的时辰化疗方案的毒性取决于患者特征。在进一步的研究中，应考虑确定化疗毒性的危险因素。由于本初步研究中的患者数量较少，这些发现需要在更大规模的临床研究中得到证实。
