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

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.

[A case of brain metastasis from advanced ovarian clear-cell carcinoma during maintenance chemotherapy with irinotecan+cisplatin].

Clear-cell carcinoma of the ovary is a highly malignant neoplasm. Survival of patients in the advanced stage is poor, and the best treatment is not clear. We report here a case of a 57-year-old woman who had Stage IIIb advanced clearcell carcinoma of the ovary. We performed abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lympho adenectomy and partial omentectomy. After the operation she was placed on induction and maintenance chemotherapy with a combination of irinotecan(CPT-11)(60 mg/m2, day 1, 15)plus cisplatin(CDDP)(60 mg/m2, day 1). Four years after surgery, a metastatic tumor was found in the brain. Considering the poor prognosis of clear-cell carcinoma, this regimen is thought to be effective for advanced clear-cell carcinoma of the ovary. It is important to check brain metastases under maintenance chemotherapy.

[A case of advanced clear cell carcinoma of the endometrium that responded remarkably to neoadjuvant chemotherapy of combination carboplatin plus weekly paclitaxel].

Clear cell carcinoma of the endometrium is a very rare and highly malignant neoplasm that accounts for less than 5% of endometrial carcinoma. Survival of patients in the advanced stage is poor, and the treatment of choice is not clear. We report the case of a 62-year-old woman who had Stage IVb advanced clear cell carcinoma of the endometrium with multiple lung metastases. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy of combination carboplatin (CBDCA) (AUC 5, day 1) plus weekly paclitaxel (PTX) (70 mg/m(2), day 1, 8, 15). After 3 courses of chemotherapy, the uterine tumor was obviously reduced, and lung metastases had disappeared. Therefore, she underwent the operation. The current case suggests that combination CBDCA plus weekly PTX is effective against advanced clear cell carcinoma of the endometrium.

Granulocyte colony-stimulating factor suppresses autologous tumor killing activity of the peripheral blood lymphocytes in the patients with ovarian carcinoma.

PROBLEM: Granulocyte colony-stimulating factor (G-CSF) is often administered to patients with chemotherapy-induced leukocytopenia. However, adequate attention has not been paid to its effects on cancer immunology. Reported by us and others, G-CSF often induces immunosuppression and down-regulation of response T helper (Th)2 directed immune reaction both in vivo and in vitro. In this study, we analyzed the effects of G-CSF on interferon (IFN)-gamma production and autologous tumor killing (ATK) activities of peripheral blood mononuclear cells (PBMCs). METHODS OF STUDY: In order to evaluate the cytokine-induced activation of peripheral T and natural killer (NK) cells, we analyzed IFN-gamma production by interleukin (IL)-2- and IL-12-stimulated PBMCs, using the ELISPOT assay. Specific killing of autologous tumor cells was evaluated by lactate dehydrogenase (LDH) release assay. RESULTS: The PBMC collected from both cancer-bearing patients and healthy subjects showed IL-2- and/or IL-12-induced IFN-gamma production. The frequency of IFN-gamma producing cells was significantly higher in the normal subjects compared with the patients with advanced ovarian carcinoma. The ATK activity was also enhanced in IL-2- and/or IL-12-stimulated PBMCs of patients with ovarian carcinoma. G-CSF almost completely abolished IFN-gamma production and ATK activity of PBMC stimulated with IL-2 and/or IL-12. CONCLUSIONS: The G-CSF appears to be a suppressor of antitumor immunity. Routine administration of G-CSF to cancer patients may not be recommended, except for febrile neutropenia.