Altern Ther Health Med. 2023 May;29(4):6-17.
Bladder cancer is the fourth-most-common cancer in males in the U.S., who develop about 90% of the high-grade, carcinoma in situ (CIS) of non-muscle involved disease (NMIBC). Smoking and occupational carcinogens are well-known causes. For females without known risk factors, bladder cancer can be regarded as a sentinel environmental cancer. It's also one of the costliest to treat due to its high rate of recurrence. No treatment innovations have occurred in nearly two decades; intravesical instillation of Bacillus Calmette-Guerin (BCG), an agent in short supply globally, or Mitomycin-C (MIT-C) is effective in about 60% of cases. Cases refractory to BCG and MIT-C often undergo cystectomy, a procedure with numerous impacts on life styles and potential complications. The recent completion of a small Phase I trial of mistletoe in cancer patients that have exhausted known treatments at Johns Hopkins provides corroboration of its safety, with 25 % showing no disease progression.
The study examined the benefits of pharmacologic ascorbate (PA) and mistletoe for a nonsmoking female patient with an environmental history of NMIBC refractory to BCG, in a non-smoking female with exposures in childhood and early adult life to several known carcinogens, including ultrafine particulate air pollution, benzene, toluene, and other organic solvents, aromatic amines and engine exhausts, and possibly arsenic in water.
The research team performed an integrative oncology case study on pharmacologic ascorbate (PA) and mistletoe, both agents shown to activate NK cells, enhance growth and maturation of T-cells, and induce dose-dependent pro-apoptotic cell death, suggesting shared and potentially synergistic mechanisms.
The study began at the University of Ottawa Medical Center in Canada with treatment continuing over six years at St. Johns Hospital Center in Jackson, Wyoming, and George Washington University Medical Center for Integrative Medicine, with surgical, cytological, and pathological evaluations at University of California San Francisco Medical Center.
The patient in the case study was a 76-year-old, well-nourished, athletic, nonsmoking female with high-grade CIS of the bladder. Her cancer was considered to be a sentinel environmental cancer.
Intravenous pharmacologic ascorbate (PA) and subcutaneous mistletoe (three times weekly) and intravenous and intravesical mistletoe (once weekly) were employed for an 8-week induction treatment, using a dose-escalation protocol as detailed below. Maintenance therapy was carried out with the same protocol for three weeks every three months for two years.
The patient has experienced a cancer-free outcome following 78 months of treatments that incorporated intravesical, intravenous, and subcutaneous mistletoe; intravenous PA; a program of selected nutraceuticals; exercise; and other supplementary treatments.
This study is the first reported instance of combined treatments to achieve complete remission for high-grade NMIBC refractory to BCG and MIT-C, using intravesical, subcutaneous, and intravenous mistletoe and intravenous PA. It includes pharmacological information on possible mechanisms. In light of the global shortage of BCG, the high proportion of cases refractory to BCG and MIT-C, the unproven use of costly off-label pharmaceuticals, such as gemcitabine, and the relative cost-effectiveness of mistletoe and PA, clinicians should give serious consideration to employing these combined functional medicine treatments for BCG- and MIT-C-refractory NMIBC. Further research is needed with additional patients that can advance our understanding, including standardization of methods for systematically evaluating combined therapies-blinded and non-blinded, nomenclature regarding mistletoe preparation, doses, concentrations, regimes of administration, lengths of treatment, targeted cancer types, and other aspects.
膀胱癌是美国男性中第四大常见癌症，约 90%的非肌肉浸润性疾病（NMIBC）高级别原位癌（CIS）发生在男性中。吸烟和职业性致癌物是已知的原因。对于没有已知风险因素的女性，膀胱癌可以被视为一种环境哨兵癌。由于其高复发率，它也是治疗费用最高的癌症之一。近 20 年来，没有治疗创新；膀胱内灌注卡介苗（BCG）或丝裂霉素-C（MIT-C）在约 60%的病例中有效。对 BCG 和 MIT-C 耐药的病例常行膀胱切除术，该手术对生活方式和潜在并发症有许多影响。最近，约翰霍普金斯大学完成了一项小型 I 期临床试验，对已用尽已知治疗方法的癌症患者使用槲寄生，证实了其安全性，其中 25%的患者没有疾病进展。
该研究检查了药理抗坏血酸（PA）和槲寄生对一名非吸烟女性患者的益处，该患者患有非肌层浸润性膀胱癌（NMIBC），对 BCG 耐药，且有环境暴露史，在儿童和成年早期接触到几种已知的致癌物，包括超细颗粒空气污染、苯、甲苯和其他有机溶剂、芳香胺和发动机废气，以及可能接触水中的砷。
研究小组对药理抗坏血酸（PA）和槲寄生进行了综合肿瘤学病例研究，这两种药物都能激活自然杀伤细胞，增强 T 细胞的生长和成熟，并诱导剂量依赖性的促凋亡细胞死亡，这表明它们具有共同的潜在协同作用机制。
该研究始于加拿大渥太华大学医学中心，治疗在怀俄明州杰克逊的圣约翰斯医院中心持续了六年，在乔治华盛顿大学医学中心的综合医学中心进行，在加利福尼亚大学旧金山医学中心进行手术、细胞学和病理学评估。
病例研究中的患者是一名 76 岁、营养良好、运动型、不吸烟的女性，患有高级别膀胱癌 CIS。她的癌症被认为是一种环境哨兵癌。
静脉内给予药理抗坏血酸（PA）和皮下槲寄生（每周三次）和静脉内和膀胱内槲寄生（每周一次）进行 8 周诱导治疗，使用如下详述的剂量递增方案。维持治疗采用相同的方案，每三个月进行三周，持续两年。
患者在接受了 78 个月的治疗后，癌症得到了完全缓解，这些治疗包括膀胱内、静脉内和皮下槲寄生；静脉内 PA；选择的营养补充剂方案；运动；和其他补充治疗。
这是首例报道的联合治疗方法，使用膀胱内、皮下和静脉内槲寄生和静脉内 PA 治疗对 BCG 和 MIT-C 耐药的高级别 NMIBC 达到完全缓解。该研究包括了可能的机制的药理学信息。鉴于卡介苗全球短缺、BCG 和 MIT-C 耐药比例高、昂贵的非标签药物（如吉西他滨）的使用未经证实，以及槲寄生和 PA 的相对成本效益，临床医生应认真考虑使用这些联合功能医学治疗方法治疗 BCG 和 MIT-C 耐药的 NMIBC。需要更多的患者进行进一步的研究，以提高我们的认识，包括系统评估联合治疗的方法标准化——盲法和非盲法、槲寄生制剂的命名、剂量、浓度、给药方案、治疗时间、靶向癌症类型和其他方面。
