Actual practice of Kochi oxydol radiation therapy for unresectable carcinomas by intra‑tumoral administration of hydrogen peroxide as a radiosensitizer

Abstract

Kochi oxydol radiation therapy for unresectable carcinomas (KORTUC) is a novel cancer treatment method developed in Japan. KORTUC targets resistance factors in cancer therapy, such as low-oxygen environments and excessive antioxidant enzymes. This may enhance the effects of conventional treatments. The present study reports the experience of the Nagasaki Prefecture Shimabara Hospital in using KORTUC treatment for a series of 210 patients between January 2010 and June 2019. When this radiosensitizer, a mixture of a dilute hydrogen peroxide solution (0.5 ml, 3%/unit) and sodium hyaluronate (2.5 ml, 0.83%/unit), is administered and applied directly to the cancer lesion, antioxidant enzymes are neutralized and degraded causing reoxygenation as a secondary by-product, thereby enhancing the cytotoxic effect of radiation. The radiosensitizer was administered twice per week before irradiation. Up to June 2019, KORTUC was administered to 210 patients. The most common disease stage was stage IV in 137 patients (65%), followed by stage III in 25 patients, stage I in 17 patients and stage II in 7 patients (unknown disease stage in 24 patients). Of the 186 patients who could be followed up after the treatment, 28 (15%) patients had a complete response (Response Evaluation Criteria in Solid Tumors version 1.1), 59 (32%) had a partial response, 73 (39%) had stable disease and 26 (14%) had progressive disease. No significant treatment-related adverse events were observed. The present study highlights the reports of 4 cases (3 cases from among the 28 patients with complete responses): i) A case of advanced, inoperable breast cancer; ii) a refractory patient with recurrence a decade after postoperative irradiation; iii) a patient with advanced, inoperable rectal cancer; and iv) a patient with lymph node metastases. Overall, KORTUC showed good efficacy and tolerable safety for various types of radioresistant tumors, and it has the potential for immediate worldwide use.

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)(10)(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.…”

“…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). They also treated 2 Stage II patients with axillary lymph node metastases: one developed a local recurrence at 12 months, and another developed brain metastasis at 35 months and died at 56 months (personal communication, December 2022).…”

“…They also treated 2 Stage II patients with axillary lymph node metastases: one developed a local recurrence at 12 months, and another developed brain metastasis at 35 months and died at 56 months (personal communication, December 2022). In addition, Obata et al [ 24 ] treated 32 patients with Stage III or IV breast cancer, and a complete or partial response was obtained in 50%. So, the treatment efficacy depends on the disease stage.…”