A phase II study of FOLFOXIRI plus bevacizumab as initial chemotherapy for patients with untreated metastatic colorectal cancer: TRICC1414 (BeTRI).

PURPOSE: FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes. METHODS: Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR). RESULTS: Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8-77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively. CONCLUSIONS: FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.

Aberrant expression of selenoproteins in the progression of colorectal cancer.

Since damage to DNA and other cellular molecules by reactive oxygen species ranks high as a major culprit in the onset and development of colorectal cancer, the aim of the present study is to clarify the role of antioxidant seleonoproteins including glutathione peroxidase (GPx), thioredoxin reductase (TXR) and selenoprotein P (SePP), and the effect of oxidative stress on the progression of colorectal cancer. Expression of 14 oxidative stress-related molecules in both tumorous and non-tumorous tissues in 41 patients was examined by immunohistochemistry and Western blot analysis. Expression levels of proteins modified by 4-hydroxy-2-nonenal (4-HNE), malonyldialdehyde (MDA) and 4-hydroxy-2-hexenal (4-HHE), and the positive rate of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in tumorous tissues were much higher than those in non-tumorous tissues. Glutathione (GSH) content in tumor tissues was much lower than that in non-tumorous tissues. Expression level of selenoproteins such as GPx-1, GPx-3, and SePP, which are rapidly degraded during selenium deprivation, was significantly decreased in tumorous tissues, whereas that of GPx-2, which is resistant to selenium deprivation, was increased. Expression of SePP was decreased at stage III and IV, compared to that of stage II. These data suggest that contrasting expression pattern of the antioxidant selenoproteins plays an important role in the progression of colorectal cancer.

[Successful combination therapy with 5'-DFUR and MPA for breast cancer with spinal and vertebral metastases].

We report a case of breast cancer with spinal and vertebral lesions. A 49-year-old premenopausal woman with a left breast tumor was admitted to our hospital for acute weakness of the lower limbs and dysuria. She could neither stand nor walk. The tumor in the left breast was 5.0 cm in diameter with skin ulcer, and it was diagnosed as breast cancer. Magnetic resonance (MR) image showed multiple vertebral and spinal metastases from breast cancer. Chemotherapy, consisting of cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) was initiated. Her symptoms dramatically changed for the better. She became able to walk and urinate. We performed palliative mastectomy after 3 cycles of CAF therapy. Histopathological findings of breast tumor showed scirrhous carcinoma. Although the estrogen and progesterone receptor status of primary tumor was negative, chemo-endocrine therapy, consisting of medroxyprogesterone acetate (MPA) and doxifluridine (5'-DFUR) was given as daily therapy, and vertebral and spinal lesions were reduced. Her condition has remained stable for 4 years. For patients with metastatic breast cancer, complete remission is uncommon, and disease stabilization is a reasonable goal of successful therapy. In this respect, therapy with CAF, followed by MPA and 5'-DFUR, was successful in the patient.