Long-term Survival, Tolerability, and Safety of First-Line Bevacizumab and FOLFIRI in Combination With Ginsenoside-Modified Nanostructured Lipid Carrier Containing Curcumin in Patients With Unresectable Metastatic Colorectal Cancer.

BACKGROUND: Colorectal cancer is the third most common malignant disease and the second leading cause of death worldwide. Previous studies showed improved bioavailability and cytotoxicity of ginsenoside-modified nanostructured lipid carrier containing curcumin (G-NLC) in human colon cancer cell lines. This study aimed to evaluate the safety and tolerability with long-term survival rates in patients with colorectal cancer with unresectable metastases after treatment with first-line bevacizumab/FOLFIRI (folinic acid, bolus/continuous fluorouracil, and irinotecan) in combination with a dietary supplement of G-NLC. METHODS: This study was a prospective, observational, single-group analysis. The enrolled patients had colorectal cancer with unresectable metastases and were administered bevacizumab and FOLFIRI in combination with daily oral G-NLC as first-line treatment. Overall survival, progression-free survival, tumor response, and adverse events were evaluated. RESULTS: A total of 44 patients were enrolled between 2015 and 2019. The median age was 65 (range 45-81) years and the sex ratio was 31:13 (male:female). The primary tumor locations were the colon (31 patients) and rectum (13 patients). The metastatic sites included, liver only (n = 20), lung only (n = 6), both liver and lung (n = 12), and others (n = 6). The median duration of curcumin supply was 7.9 (range 0.9-16.6) months. The most common grade 3 or higher adverse events were neutropenia (n = 15, 34.1%), followed by nausea (n = 4, 9.1%) and vomiting (n = 4, 9.1%). Within the median follow-up period of 22.8 months, the median overall survival was 30.7 months, and the median progression-free survival was 12.8 months. None of the patients achieved complete response (CR); however, 9 patients showed partial response (PR), and 3 patients underwent conversion surgery. CONCLUSIONS: Bevacizumab/FOLFIRI with G-NLC as first-line chemotherapy in patients with colorectal cancer with unresectable metastases presented comparable long-term survival outcomes with acceptable toxicity outcomes. Additional randomized controlled studies are needed to establish definitive conclusions regarding this new regimen for metastatic colorectal cancer.

Impact of Mitomycin-C-Induced Neutropenia after Hyperthermic Intraperitoneal Chemotherapy with Cytoreductive Surgery in Colorectal Cancer Patients with Peritoneal Carcinomatosis.

BACKGROUND: Mitomycin-C (MMC) is the most commonly used chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS). However, MMC has a side effect of myelosuppression. This study aimed to evaluate the clinical manifestations and impact of MMC-induced neutropenia after CRS and HIPEC in colorectal cancer patients. METHODS: A total of 124 colorectal cancer patients who underwent CRS with HIPEC between March 2015 and January 2019 were evaluated. Patients with malignancies of non-colorectal origin, hospital stay longer than 60 days, peritoneal cancer index > 30, and complete cytoreduction score > 2 were excluded. MMC 35 mg/m2 was administered for 90 min at 41-43 °C. The patients were divided into three groups: no neutropenia, mild neutropenia (grade 1-2), and severe neutropenia (grade 3-4). RESULTS: In total, mild and severe neutropenia occurred in 30 (24.2%) and 48 (38.7%) patients, respectively. Age and body surface area were significantly different among the neutropenia groups. Severe neutropenia developed significantly earlier than mild neutropenia (6.9 days vs. 10.4 days, p < 0.001) and also lasted significantly longer (4.6 days vs. 2.5 days, p = 0.005). The rate of major postoperative complications was significantly higher in the severe neutropenia group than in the no and mild neutropenia groups (8.3% vs. 6.7% vs. 6.5%, p = 0.015) CONCLUSIONS: Severe neutropenia starts earlier and lasts longer than mild neutropenia after CRS and HIPEC using an MMC triple method. The higher rate of major postoperative complications in patients with severe neutropenia highlights the importance of postoperative management during the neutropenia period.

Effect of mistletoe extract on tumor response in neoadjuvant chemoradiotherapy for rectal cancer: a cohort study.

BACKGROUND: Mistletoe extract, used as a complementary chemotherapeutic agent for cancer patients, has anticancer effects against various malignancies. The aim of the present study was to evaluate the effect of mistletoe extract (Abnoba Viscum Q®) on tumor responses to neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer. METHODS: This study included patients with rectal cancer who underwent NCRT between January 2018 and July 2020. In the mistletoe group (MG), the patients were administered Abnoba Viscum Q® subcutaneously during chemoradiotherapy-maintained just before surgery. Patient demographics, clinical outcomes, histopathological outcomes, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) assay results were compared between the MG and non-mistletoe group (NMG). Two rectal cancer cell lines (SNU-503 and SNU-503R80Gy) were treated with Abnoba Viscum Q® to assess its mechanistic effects in vivo. RESULTS: Overall, the study included 52 patients (MG: n = 15; NMG: n = 37). Baseline demographics between the two groups were similar, except carbohydrate antigen 19-9 levels and tumor location from the anal verge. There was no difference in the clinical stage between the two groups. A better tumor response in the MG, relative to the NMG, was observed with respect to tumor regression grade (TRG), T stage, and overall tumor-node-metastasis stage. Tumor response was significantly better in the MG than in the NMG in terms of pathologic complete response rate (53.3% vs. 21.6%, P = 0.044), good TRG response (66.7% vs. 32.4%, P = 0.024), T downstaging (86.7% vs. 43.2%, P = 0.004), and overall downstaging (86.7% vs. 56.8%, P = 0.040). The toxicities during NCRT were minimal in both groups. More apoptotic cells were noted in MG samples than in the NMG samples on TUNEL staining. Cleaved caspase-3 level following treatment with Abnoba Viscum Q® was higher in SNU-503R80Gy cells than in SNU-503 cells. CONCLUSION: Patients treated with chemoradiation combined with mistletoe extract showed better outcomes than patients not treated with mistletoe extract in terms of tumor responses. This diversity in treatment may improve the efficacy of NCRT, leading to better oncologic outcomes. Prospective and randomized studies with long-term follow-up are warranted to confirm and extend these results.

Clinical outcomes of complete cytoreduction with concurrent liver resection followed by hyperthermic intraperitoneal chemotherapy for synchronous peritoneal and liver metastatic colorectal cancer.

BACKGROUND: This study aimed to evaluate the clinical outcomes of concurrent liver resection with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in colorectal cancer patients with synchronous liver and peritoneal metastases. METHODS: Patients with colorectal liver and peritoneal metastasis who underwent complete cytoreduction and hyperthermic intraperitoneal chemotherapy with concurrent liver surgery between September 2014 and July 2018 were included. Perioperative outcomes, overall survival, and progression-free survival were analyzed retrospectively. RESULTS: In total, 22 patients were included. The median peritoneal cancer index was 13 (range, 0-26), and the median number of liver metastases was 3 (range, 1-13). The mean total operative time was 11.4 ± 2.6 h. Minor postoperative complications (Clavien-Dindo grade I-II) were reported in 10 patients (45.5%), and major postoperative complications (grade III-V) were reported in five patients (22.7%), including one mortality patient. The median overall survival since diagnosis with metastasis was 27.4 months. The median overall survival since surgical intervention and the progression-free survival were 16.7 months and 7.1 months, respectively. CONCLUSIONS: This short-term follow-up study showed that, in an experienced center, combined resection with hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases was feasible and safe with acceptable oncologic outcomes.