Therapeutic response to a novel enzyme-targeting radiosensitization treatment (Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas) in patients with recurrent breast cancer

Abstract

Linear accelerator-based radiotherapy has little effect on the majority of locally advanced neoplasms. Thus, the novel radiosensitizer Kochi Oxydol Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), which contains hydrogen peroxide and sodium hyaluronate, was developed. The effectiveness of KORTUC II for the treatment of chemotherapy-resistant supraclavicular lymph node metastases has been previously demonstrated. The present study evaluated the safety and effectiveness of KORTUC II in patients with recurrent breast cancer. A total of 20 patients (age range, 39–84 years) were enrolled in the study. The majority of patients underwent positron emission tomography (PET)-computed tomography (CT) examinations prior to and 1–7 months following KORTUC II treatment, and every 6 months thereafter when possible. The radiotherapy regimen was 2.75 Gy/fraction, 5 fractions/week, for 16–18 fractions, with a total radiation dose of 44.00–49.50 Gy (X-ray irradiation), or 4.00 Gy/fraction, 3 fractions/week, for 10–12 fractions, with a total radiation dose of 40.00–48.00 Gy (electron beam irradiation). The injection of 3–6 ml of the KORTUC II agent was initiated at the fifth radiotherapy fraction, and was performed twice/week under ultrasonographic guidance. The therapeutic effects were evaluated by PET-CT examinations prior and subsequent to KORTUC II treatment, which was observed to be well tolerated with minimal adverse effects. Of the 24 lesions presented by the 20 patients, 18 exhibited complete response, 5 partial response, 0 stable disease and 1 progressive disease. The overall survival rate was 100% at 1 year and 95% at 2 years. The mean duration of follow-up at the end of June 2014 was 51 months. Based on the results of the PET-CT studies conducted, KORTUC II treatment demonstrated marked therapeutic effects, with satisfactory treatment outcomes and acceptable adverse events.

Therapeutic response to a novel enzyme-targeting radiosensitization treatment (KORTUC II) for residual lesions in patients with stage IV primary breast cancer, following induction chemotherapy with epirubicin and cyclophosphamide or taxane

“…The final solution of the radiosensitizer had a sodium hyaluronate concentration of ~0.83% and a hydrogen peroxide concentration of ~0.5%. The radiosensitizer solution was the same as the solution administered for the treatment of chemotherapy-resistant supraclavicular lymph node metastates and recurrent breast cancers in our previous studies (9,10). …”

“…Through the application of these treatments, certain types of cancer may be cured; however, various specific types of cancer contain numerous hypoxic cancer cells and antioxidant enzymes that may confer resistance to radiotherapy (1–3). In addition to increasing tissue oxygen concentrations, it is important to inactivate antioxidant enzymes, including peroxidase and catalase, which protect cancer cells from oxidative stress (1–10). Hydrogen peroxide is able to inactivate antioxidant enzymes and produce oxygen when applied topically to cancer tissues (1–3).…”

“…By adding hyaluronic acid to hydrogen peroxide the decomposition of hydrogen peroxide is delayed, and a high oxygen concentration is maintained in the cancer tissues for over 24 h (1–3). As reported in our previous studies (5,9,10), a novel radiosensitizer, Kochi Oxydol Radiation Therapy for Unresectable Carcinomas II (KORTUC II), was developed for the treatment of cancers that contain numerous hypoxic cancer cells and antioxidant enzymes. The components of KORTUC II are sodium hyaluronate 0.83% w/v and hydrogen peroxide 0.5% w/v.…”

“…The components of KORTUC II are sodium hyaluronate 0.83% w/v and hydrogen peroxide 0.5% w/v. The concept of KORTUC II is to transform radioresistant cancer into radiosensitive cancer (9,10). Following KORTUC II therapy, hypoxic and radioresistant cancer cells become hyperoxic and radiosensitive (Figure 1).…”

“…Following KORTUC II therapy, hypoxic and radioresistant cancer cells become hyperoxic and radiosensitive (Figure 1). In our previous studies, the efficacy of KORTUC II in the treatment of supraclavicular lymph node metastates and recurrent breast cancers was demonstrated in humans (9,10). The aim of the current study is to evaluate the safety and effectiveness of KORTUC II in patients with stage IV primary breast cancer, following induction chemotherapy with epirubicin combined with cyclophosphamide and paclitaxel or docetaxel.…”