Phase II clinical trial of local use of GM-CSF for prevention and treatment of chemotherapy- and concomitant chemoradiotherapy-induced severe oral mucositis in advanced head and neck cancer patients: an evaluation of effectiveness, safety and costs.
Phase II clinical trial of local use of GM-CSF for prevention and treatment of chemotherapy- and concomitant chemoradiotherapy-induced severe oral mucositis in advanced head and neck cancer patients: an evaluation of effectiveness, safety and costs.
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局部使用GM-CSF预防和治疗晚期头颈癌患者化疗和同步放化疗引起的严重口腔粘膜炎的II期临床试验：有效性、安全性和成本评估。
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发表时间：
2003
期刊：
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通讯作者：
A. Macciò
中科院分区：
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作者：
G. Mantovani;E. Massa;G. Astara;V. Murgia;G. Gramignano;M. Lusso;Paolo Camboni;L. Ferreli;M. Mocci;S. Perboni;L. Mura;C. Madeddu;A. Macciò
在目前的开放非随机II期研究中，我们研究了局部应用GM-CSF预防或治疗头颈癌化疗或放化疗患者粘膜炎的有效性、安全性、耐受性和成本。除了临床粘膜炎评分系统外，GM-CSF治疗的效果还通过其对患者生活质量的影响以及血清促炎细胞因子、IL-2和瘦素等实验室免疫学分析来评估。该试验旨在评估两种不同情况下GM-CSF局部治疗的有效性：1)预防粘膜炎；Ii)治疗粘膜炎。对高黏膜毒性的放化疗选择预防治疗，而对诱导黏膜炎的可能性较小的化疗或放化疗保留根治性治疗。从1998年1月到2001年12月，68名患者进入研究。两组患者绝大多数患有头颈癌，为IV期，PS ECOG 0-1，习惯性吸烟者，接受化疗和合并（或序贯）放化疗。46名患者被纳入“预防性”组，22名患者被纳入“治疗性”组。我们研究的主要发现是：在“预防性”治疗组中，只有50%的患者发生了黏膜炎；口腔黏膜炎从出现到完全缓解的持续时间在“预防”组明显短于“治疗”组；在基线、治疗第3天和治疗第6天，“预防”组口腔黏膜炎的平均等级显著低于“治疗”组；“预防”组24例（55.82%）患者基线时为3/4级口腔黏膜炎，而“治疗”组25例（80.60%）患者基线时为3/4级（p=0.048）。预防组13例（30.23%）患者在治疗第3天出现3/4级口腔黏膜炎，治疗组19例（61.29%）患者出现3/4级口腔黏膜炎（p=0.015）；在治疗第6天，“预防性”组比“治疗性”组能更有效地将3/4级口腔黏膜炎缩短至0/1级（p=0.05）。目前的临床试验是迄今为止评估外用GM-CSF有效性的最大规模的研究，也是第一个比较外用GM-CSF在“预防性”环境下（即旨在预防放化疗引起的口腔黏膜炎）与“治愈性”治疗（即治疗已建立的口腔黏膜炎）疗效的研究。GM-CSF外用对化疗和放化疗引起的口腔黏膜炎有效。此外，“预防性”的设置被证明比“治疗性”的设置更有效。
In the present open non-randomized phase II study we looked for effectiveness, safety, tolerability and costs of locally applied GM-CSF in preventing or treating mucositis in patients receiving chemotherapy or chemoradiotherapy for head and neck cancer. In addition to clinical mucositis scoring system, the effects of treatment with GM-CSF were evaluated by its impact on patient quality of life and by laboratory immunological assays such as serum proinflammatory cytokines, IL-2 and leptin. The trial was designed to assess the effectiveness of local GM-CSF treatment in two different settings: i) prophylaxis of mucositis; ii) treatment of mucositis. Prophylaxis was chosen for chemoradiotherapy treatments of high mucosatoxic potential, while curative treatment was reserved for chemotherapy or chemoradiotherapy treatments of lesser potential of inducing mucositis. From January 1998 to December 2001, 68 patients entered the study. The great majority of patients of both groups had head and neck cancer, were stage IV, PS ECOG 0-1, were habitual smokers and were treated with chemotherapy and concomitant (or sequential) chemoradiotherapy. Forty-six patients were included in the 'prophylactic' setting and 22 patients in the 'curative' setting. The main findings of our study are: only 50% of patients included in the 'prophylactic' setting developed mucositis; the duration of oral mucositis from appearance until complete remission was significantly shorter in the 'prophylactic' than in the 'curative' setting; the mean grade of oral mucositis at baseline, on day 3 of therapy and on day 6 of therapy was significantly lower in the 'prophylactic' than in the 'curative' setting; 24 (55.82%) patients in the 'prophylactic' setting had grade 3/4 oral mucositis at baseline compared to 25 (80.60%) patients in the 'curative' setting (p=0.048). Thirteen (30.23%) patients in the 'prophylactic' setting had grade 3/4 oral mucositis on day 3 of therapy compared to 19 (61.29%) patients in the 'curative' setting (p=0.015); 'prophylactic' setting was able to shorten grade 3/4 oral mucositis to grade 0/1 more effectively than the 'curative' one on day 6 of therapy (p=0.05). The present clinical trial is to date by far the largest study assessing the effectiveness of topical GM-CSF and it is the first study comparing the efficacy of topical GM-CSF in the 'prophylactic' setting, i.e., with the aim to prevent the chemoradiotherapy-induced oral mucositis, with that in the 'curative' treatment, i.e., the therapy for established oral mucositis. The topical application of GM-CSF was demonstrated to be effective for oral mucositis induced by chemotherapy and chemoradiotherapy regimens. Moreover, the 'prophylactic' setting was demonstrated to be more effective than the 'curative' one.