A phase II clinical trial of interleukin-2 and lymphokine-activated killer cells in advanced colorectal carcinoma.
A phase II clinical trial of interleukin-2 and lymphokine-activated killer cells in advanced colorectal carcinoma.
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白细胞介素-2 和淋巴因子激活杀伤细胞治疗晚期结直肠癌的 II 期临床试验。
DOI：
10.1097/00002371-199401000-00010
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
Paietta,E
中科院分区：
文献类型：
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作者：
Hawkins,MJ;Atkins,MB;Dutcher,JP;Fisher,RI;Weiss,GR;Margolin,KA;Rayner,AA;Sznol,M;Parkinson,DR;Paietta,E
在IL-2/LAK工作组(ILWG)进行的II期研究中，22例转移性或无法切除的结直肠癌患者接受了IL-2和淋巴因子激活的杀伤(LAK)细胞的治疗。这项研究的资格标准包括可二维测量的疾病、功能状态为0或1，以及所有重要器官的正常功能。患者的中位年龄为49岁(范围28-61岁)。8名患者(36%)除了最初的手术外从未接受过其他治疗；8名患者(36%)接受过放射治疗，12名患者(55%)接受过化疗。没有患者之前接受过免疫治疗。治疗包括IL-2，60万IU/kg，在第1-5天和12-16天静脉滴注15min，每8h一次。患者在第8~12天进行4h的白细胞分离，将细胞置于含有IL-2的体外培养3~4天，并在第12、13和15天输注活化的LAK细胞超过1h。第1~5天给药平均+/-SD为13.4+/-1.2，回输LAK细胞平均为6.8+/-2.2×10‘[度]，末次给药平均为9.8+/-2.5次。19例患者完成了IL-2预备期，并接受了至少一次LAK细胞输注。1例患者完全缓解，自治疗开始后8个月内无进展，总体客观有效率为5%(95%可信区间：0-13%)。低血压、体重增加、贫血以及血清肌酐和肝酶升高是常见的，但没有与治疗相关的死亡。所提供的治疗和毒性与同时对其他恶性肿瘤进行的研究中报告的结果相当。我们的结论是，高剂量的IL-2在转移性结直肠癌中的活性很低；然而，低水平的活性不应排除未来将IL-2与其他免疫治疗方法相结合的研究。
Patients (n='22) with metastatic or unresectable colorectal carcinoma were treated with interleukin (IL)-2 and lymphokine-activated killer (LAK) cells in a phase II study conducted by the IL-2/LAK Working Group (ILWG). Eligibility criteria for the study included bidimensionally measurable disease, performance status 0 or 1, and normal function of all vital organs. The median age of patients was 49 (range, 28-61) years. Eight (36%) patients had never received prior treatment other than their initial surgery; eight (36%) had received prior radiotherapy, and 12 (55%) chemotherapy. No patients had received prior immunotherapy. Treatment consisted of IL-2, 600,000 IU/kg administered by 15-min intravenous infusion every 8 h on days 1-5 and 12-16. Patients underwent 4-h leukapheresis on days 8-12, and cells were placed in in vitro culture with IL-2 for 3-4 days and the activated LAK cells were infused over 1 h on days 12, 13, and 15. AH doses of IL-2 and LAK cells were administered to patients in intensive care unit (ICU) settings. The mean+/-SD number of IL-2 doses administered during days 1-5 was 13.4+/-1.2, the mean number of LAK cells reinfused was 6.8+/-2.2 x 10'[degrees], and the mean number of IL-2 doses administered during the last phase was 9.8+/-2.5. Nineteen patients completed the IL-2 priming phase and received at least one LAK cell infusion. One patient achieved a complete response and was progression free for 8 months from the beginning of treatment, for an overall objective response rate of 5%(95% confidence interval: 0-13%). Hypotension, weight gain, anemia, and elevations of serum creatinine and liver enzymes were common, but there were no treatment-related deaths. Treatment delivered and toxicity were comparable to those reported in studies conducted concurrently for other malignancies. We conclude that high-dose IL-2 has minimal activity in metastatic colorectal cancer; however, the low level of activity should not preclude future studies combining IL-2 with other immunotherapeutic approaches.