Background/Objectives: Functional p53 is critical for anti-tumor activity of mitomycin-C. In wild-typeTP53human papillomavirus (HPV)-positive squamous cell carcinoma (SCC) cell lines, mitomycin-C repressed E6 oncoprotein expression and induced p53, p21, and Bax, resulting in apoptosis. In mutantTP53HPV-negative SCC cell lines, mitomycin-C was inactive. The primary aim of this trial was to determine the objective response rate (ORR) with mitomycin-C among patients with HPV-positive (cohort A) and HPV-negative (cohort B) platinum-refractory, recurrent or metastatic head and neck SCC (RM-HNSCC). Methods: Patients with platinum-refractory RM-HNSCC received mitomycin-C (10 mg/m2on day one every five weeks) until discontinuation criteria were met. Tumor response was assessed by RECIST1.1. We hypothesized an ORR of ≥30% (H1) with mitomycin-C (vs. H0ORR of ≤10%). Using a two-stage Simon phase 2 design for each cohort, 2 or more responses among 12 evaluable patients were required to enroll 23 additional patients. H1was accepted if 6 or more responses occurred among 35 evaluable patients (power 0.90; one-sided α = 0.10). Results: Forty-seven patients were treated with mitomycin-C: 34 in cohort A and 13 in cohort B. Tumor response occurred in 3 of 33 evaluable patients in cohort A (ORR 9.1%, 95%CI: 0–19.4) and in 0 of 12 evaluable patients in cohort B. The duration of tumor responses in cohort A was 2.3, 2.5, and 4.5 months. The most common treatment-related AEs of any grade were anemia (96%), fatigue (62%), and thrombocytopenia (40%). No treatment-related deaths occurred. Conclusions: Mitomycin-C had limited activity in HPV-positive, and no activity in HPV-negative, platinum-refractory RM-HNSCC.
背景/目的：功能性p53对丝裂霉素C的抗肿瘤活性至关重要。在野生型TP53人乳头瘤病毒（HPV）阳性鳞状细胞癌（SCC）细胞系中，丝裂霉素C抑制E6癌蛋白表达并诱导p53、p21和Bax，从而导致细胞凋亡。而在突变型TP53 HPV阴性SCC细胞系中，丝裂霉素C无活性。本试验的主要目的是确定丝裂霉素C在HPV阳性（队列A）和HPV阴性（队列B）铂类耐药、复发或转移性头颈部鳞状细胞癌（RM-HNSCC）患者中的客观缓解率（ORR）。方法：铂类耐药的RM-HNSCC患者接受丝裂霉素C治疗（每五周第一天给药10 mg/m²），直至达到停药标准。肿瘤反应通过RECIST1.1标准评估。我们假设丝裂霉素C的ORR≥30%（H1），而零假设（H0）为ORR≤10%。采用两阶段Simon二期设计，每个队列需在12例可评估患者中出现2例或以上缓解，方可继续入组23例患者。若35例可评估患者中出现6例或以上缓解，则接受H1假设（检验效能0.90；单侧α=0.10）。结果：47例患者接受了丝裂霉素C治疗：队列A34例，队列B13例。队列A中33例可评估患者中有3例出现肿瘤缓解（ORR 9.1%，95%CI：0–19.4），队列B中12例可评估患者均未缓解。队列A中肿瘤缓解持续时间分别为2.3、2.5和4.5个月。最常见的各级治疗相关不良事件为贫血（96%）、疲劳（62%）和血小板减少（40%）。无治疗相关死亡发生。结论：丝裂霉素C在HPV阳性铂类耐药RM-HNSCC中疗效有限，在HPV阴性患者中无活性。
肿瘤(癌症)患者之家