Barrera J L, Verastegui E, Meneses A, Zinser J, de la Garza J, Hadden J W
Department of Surgery, National Institute of Cancerology, Mexico City, Mexico.
Arch Otolaryngol Head Neck Surg. 2000 Mar;126(3):345-51. doi: 10.1001/archotol.126.3.345.
To test the efficacy of a natural cytokine mixture (IRX-2), cyclophosphamide, indomethacin, and zinc to induce immune regression of squamous cell carcinoma (SCC) of the head and neck (H&N) prior to conventional therapy and to characterize the responses.
A phase 2 trial was performed in 15 adults with recently diagnosed, biopsy-confirmed H&N SCC (3 with stage II disease, 6 with stage III disease, and 6 with stage IV disease). The patients were treated with 20 days of perilymphatic injections of IRX-2 (administered subcutaneously at the base of the skull) in combination with contrasuppression consisting of a low-dose infusion of cyclophosphamide (300 mg/m2), and daily oral indomethacin and zinc (StressTabs) in a 21-day cycle before surgery and/or radiotherapy. Tumor dimensions, toxic effects, and disease-free survival were monitored. The tumor sections were histologically examined after surgery, and tumor reduction, fragmentation, and lymphoid infiltration were assessed.
All 15 patients responded clinically to the 21-day IRX-2 protocol: 1 with a complete response, 7 with a partial response, and 7 with a minor response. All 15 patients responded pathologically with tumor reduction (mean, 42%) and fragmentation (mean, 50%) in the histological section and increased lymphoid infiltration. The adverse effects of the IRX-2 protocol were negligible except for an allergic skin rash (n = 1) and parotiditis (n = 1). Indomethacin caused gastritis in 1 patient. Reduction of pain and ulceration and bleeding were observed in 8 and 4 patients, respectively. Four of 5 patients with lymphopenia showed increased CD3, CD4, and CD8 cell counts. After surgery (n = 13) and/or radiotherapy (n = 10) and with a mean follow-up of 17 months, 3 patients have had recurrences, 1 patient has died of disease, 1 patient has been re-treated with immunotherapy and has no evidence of disease, and 1 patient is alive with disease. Two patients died of other causes with no evidence of disease.
The IRX-2 immunotherapy induced lymphocyte mobilization and infiltration in H&N SCC associated with clinical and histological tumor responses indicative of immune regression in all 15 patients. Minimal toxic effects were observed, and overall survival may have been improved. A phase 3 trial seems warranted.
测试一种天然细胞因子混合物（IRX-2）、环磷酰胺、吲哚美辛和锌在常规治疗前诱导头颈部鳞状细胞癌（H&N SCC）免疫消退的疗效，并对反应进行特征描述。
对15名近期诊断、经活检确诊为H&N SCC的成年人进行了一项2期试验（3例为II期疾病，6例为III期疾病，6例为IV期疾病）。患者在手术和/或放疗前，接受为期20天的经淋巴注射IRX-2（在颅底皮下注射），并联合由低剂量环磷酰胺输注（300 mg/m²）、每日口服吲哚美辛和锌（应激片）组成的抗抑制治疗，治疗周期为21天。监测肿瘤大小、毒性作用和无病生存期。术后对肿瘤切片进行组织学检查，评估肿瘤缩小、破碎和淋巴细胞浸润情况。
所有15例患者对为期21天的IRX-2方案均有临床反应：1例完全缓解，7例部分缓解，7例轻微缓解。所有15例患者在组织学切片上均有病理反应，表现为肿瘤缩小（平均42%）和破碎（平均50%），淋巴细胞浸润增加。IRX-2方案的不良反应可忽略不计，仅1例出现过敏性皮疹，1例出现腮腺炎。吲哚美辛导致1例患者出现胃炎。分别有8例和4例患者疼痛、溃疡和出血减轻。5例淋巴细胞减少的患者中有4例CD3、CD4和CD8细胞计数增加。术后（n = 13）和/或放疗后（n = 10），平均随访17个月，3例患者复发，1例患者死于疾病，1例患者接受免疫治疗后再次治疗且无疾病证据，1例患者带瘤生存。2例患者死于其他原因，无疾病证据。
IRX-2免疫疗法在15例患者中均诱导了淋巴细胞动员和浸润，与临床和组织学肿瘤反应相关，表明免疫消退。观察到的毒性作用极小，总体生存期可能有所改善。似乎有必要进行3期试验。
