New enzyme‑targeting radiosensitizer (KORTUC II) treatment for locally advanced or recurrent breast cancer

Abstract

Kochi oxydol radiation therapy for unresectable carcinomas II (KORTUC II) is currently the most widely used radiosensitizer in Japan. This sensitizer is a solution consisting of 0.83% sodium hyaluronate and 0.5% hydrogen peroxide. The mixture is injected intratumorally just before radiation therapy (RT) several times. KORTUC II has the effect of neutralizing antioxidant enzymes, while increasing the oxygen tension into the tumor tissue, and achieves marked local effects without notable adverse events. The present report describes cases in which KORTUC II was used to treat patients with locally advanced breast cancer (LABC) or recurrent breast cancer (LRBC). The present study included 30 patients with LABC (n=9) or LRBC (n=21) aimed at local control of tumors, who were followed up for ≥3 months after treatment. The irradiation dose and extent fields were determined by the attending physicians considering various patient factors, such as a performance status, prognosis and presence or absence of adjuvant therapy. The median irradiation dose was 60.4 Gy3.5 (43.6-76.1 Gy3.5) based on the calculation of equivalents of 2 Gy fractions, and the median total number of sensitizer injections was 5 ( 2-7 ) times. The median maximum tumor shrinkage was 97.0% and 15 patients (50%) were assessed to have achieved a clinical complete response. The proportion with loco-regional control at 1, 2 and 3 years was 100, 94.7 and 75.4%, respectively, and progression free survival after RT at 1 and 2 years was 59.0 and 24.1%, respectively. KORTUC II exhibited high rates of local tumor control for LABC and LRBC. KORTUC II is expected to be an inexpensive and promising RT method because it is safe and has an excellent radio-sensitizing effect.

KORTUC, a novel hydrogen peroxide‑based radiosensitizer for the enhancement of brachytherapy in patients with unresectable recurrent uterine cervical cancer

“…In agreement with previous studies, KORTUC had almost no adverse events associated with intratumor injection ( 9 – 11 , 27 ).…”

“…A phase 2 clinical trial for locally advanced/recurrent breast cancer is ongoing in the UK and India (NCT03946202). In addition, several clinical studies on various solid tumors are ongoing in Japan (6)(7)(8)(9)(10)(11). Clinical research on KORTUC at our institution has been conducted since May 2010; as of April 2023, ~250 patients with various solid cancers received this treatment, including >40 patients with gynecological cancers treated with brachytherapy (BT) and KORTUC.…”

Non-Surgical Definitive Treatment for Operable Breast Cancer: Current Status and Future Prospects

“…Following the study of Ogawa et al [ 19 , 20 , 21 ], several groups used the intratumoral hydrogen peroxide radiosensitization method to treat breast cancer [ 6 , 7 , 8 , 23 , 24 ]. Table 1 summarizes the results reported so far.…”

“…Table 1 summarizes the results reported so far. Subsequent investigators treated more advanced cases, and the treatment outcomes were not as good as those of Ogawa et al Shimbo et al [ 23 ] treated 30 patients with locally advanced or recurrent breast cancer employing the KORTUC method, and the 3-year local control rate was 75%; the 2-year progression-free survival rate was only 24%. Obata et al [ 24 ] treated 5 patients with Stage I breast cancer with KORTUC, and no local recurrences or distant metastases have been observed during a median follow-up period of 65 months (range, 47–91 months).…”

Intratumoral pro-oxidants promote cancer immunotherapy by recruiting and reprogramming neutrophils to eliminate tumors

“…Thus, in recently reported Phase I clinical trials of locally advanced breast cancer, the use of ultrasound guided intratumoral injection of 0.5% H2O2 and 0.83% sodium hyaluronate in a gel (to slow H2O2 release and promote anticancer activity), 1 h prior to radiotherapy (36–49.5 Gy dose), was well tolerated and maintained partial or complete tumor responses relative to baseline in 11 out of 12 patients [ 136 ]. A second report followed in 2021 and the procedure is now known as Kochi Oxydol Radiation Therapy for Unresectable Carcinomas II (KORTUC II), purported to be the most widely used radiosensitizer in Japan today [ 137 ]. The second study described the results from 30 patients with locally advanced or recurrent breast cancers recording a median maximum tumor shrinkage of 97.0% and 15 patients (50%) were assessed to have achieved a clinical complete response.…”