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

Abstract

Linac-based radiotherapy has a negligible effect on the majority of advanced neoplasms. Therefore, a novel radiosensitization treatment Kochi Oxydol Radiation Therapy for Unresectable Carcinomas II (KORTUC II), which utilizes hydrogen peroxide and sodium hyaluronate was developed. The effectiveness of KORTUC II for the treatment of chemotherapy-resistant supraclavicular lymph node metastases and recurrent breast cancers has previously been demonstrated. The present study evaluated the safety and efficacy of KORTUC II in patients with stage IV primary breast cancer. Seven patients (age range, 36–65 years) were enrolled. All patients received induction chemotherapy prior to KORTUC II treatment and underwent positron emission tomography-computed tomography (PET-CT) examinations prior to and 2–7 months following KORTUC II treatment, and every six months thereafter where possible. The radiotherapy regimen (x-ray irradiation) was 2.75 gray (Gy)/fraction, 5 fractions/week for 16–18 fractions with a total radiation dose of 44–49.5 Gy. Administration of the KORTUC II agent (3–6 ml: 3 ml for a lesion <3 cm in diameter and 6 ml for a lesion ≥3 cm) was initiated from the sixth radiotherapy fraction, and was conducted twice a week under ultrasonographic guidance. The therapeutic effects were evaluated by PET-CT examinations prior to and following KORTUC II treatment. Of the seven lesions from the seven patients, five exhibited complete responses, two exhibited partial responses and none exhibited stable disease or progressive disease. The overall survival rate was determined to be 100% at 1 and 86% at 2 years post-treatment. The mean duration of follow-up by December 2014 was 51 months. The results of the PET-CT studies indicated that KORTUC II treatment demonstrated marked therapeutic effects with satisfactory treatment outcomes and acceptable adverse effects.

Intratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial

“…A tumor bed boost dose increased the EQD 2 to that comparable with 36 Gy in 6 fractions and with dose intensities previously reported in earlier patient cohorts treated with the same drug preparation. 16,17…”

Therapeutic results of a novel enzyme-targeting radiosensitization treatment, Kochi oxydol-radiation therapy for unresectable carcinomas II, in patients with stage I primary breast cancer

“…The solution was mixed well to prepare the radiosensitizer, with a final sodium hyaluronate concentration of 0.83% and a hydrogen peroxide concentration of ~0.5%. The constituents of the radiosensitizer were the same as those used in previous studies for the treatment of chemotherapy-resistant supraclavicular lymph node metastases, recurrent breast cancer and stage IV primary breast cancer (18–20). …”

“…With KORTUC II treatment, radioresistant tumors become radiosensitive. Adapted from (18–20). KORTUC II, Kochi oxydol-radiation therapy for unresectable carcinomas.…”

“…For these types of cancer, the novel radiosensitizer Kochi oxydol-radiation therapy for unresectable carcinomas (KORTUC) II has been developed, the concept of which is presented in Fig. 1 (18–20). Through the use of KORTUC II, hypoxic and radioresistant cancer cells become hyperoxic and radiosensitive, with demonstrable therapeutic effects (16–26).…”

“…Through the use of KORTUC II, hypoxic and radioresistant cancer cells become hyperoxic and radiosensitive, with demonstrable therapeutic effects ( 16 – 26 ). In our previous studies, the effectiveness of KORTUC II for the treatment of supraclavicular lymph node metastases, recurrent breast cancer and stage IV primary breast cancer was demonstrated ( 18 – 20 ). According to the aforementioned strategy, the purpose of this study was to evaluate the safety and efficacy of KORTUC II in patients with stage I primary breast cancer that was not treated with surgery.…”