Prolonged administration of the granisetron transdermal delivery system reduces capecitabine plus oxaliplatin regimen induced nausea and vomiting.

OBJECTIVE: To evaluate the safety and efficacy of the granisetron transdermal delivery system (GTDS) combined with Dexamethasone for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving Capecitabine plus Oxaliplatin (CapeOX) therapy. DESIGN: Open-label, prospective, multi-center phase II trial. SETTING: Three institutions. PARTICIPANTS: Fifty-four patients scheduled to receive CapeOX chemotherapy. INTERVENTIONS: Participants received GTDS (3.1 mg applied to the upper arm 48 h before chemotherapy, replaced on day 5, and discarded on day 12) and Dexamethasone. MAIN OUTCOME MEASURES: The primary endpoint was the complete control rate of CINV. Secondary endpoints included the duration of delayed complete control, complete control rate in the acute phase, safety, and quality of life. RESULTS: The complete control rate for delayed CINV over the entire period (25-480 h) was 72.7% (95% CI 0.57-0.88). The duration of delayed complete control was 17.2 ± 4.5 days, with 51.5% of patients experiencing no nausea during the delayed phase. The complete control rate in the acute phase was 81.8% (95% CI 0.69-0.95). No serious adverse events related to the antiemetic regimen were reported. CONCLUSION: Prolonged administration of GTDS is safe and effective for preventing CINV in patients with gastrointestinal malignancies treated with CapeOX. TRIAL REGISTRATION: ClinicalTrials.gov registry (NCT05325190); registered on October 10, 2021.

Sintilimab plus bevacizumab and CapeOx (BBCAPX) on first-line treatment in patients with RAS mutant, microsatellite stable, metastatic colorectal cancer: study protocol of a randomized, open-label, multicentric study.

BACKGROUND: Rat sarcoma viral oncogene homolog (RAS) gene mutation is a common molecular event in colorectal cancer (CRC). The prognosis of mCRC (metastatic colorectal cancer) patients with RAS mutation is poor and capecitabine and oxaliplatin (CapeOx) plus bevacizumab has shown to be one of the standard therapeutic regimens as first line for these patients with objective response rate (ORR) of ~ 50% and median progression-free survival (mPFS) of 8-9 months. Immunotherapy, especially anti-programmed death 1 (PD-1) monoclonal antibody has demonstrated ground-breaking results in deficient mismatch repair (dMMR) / microsatellite instability-high (MSI-H) mCRC patients. However, the response rate of in microsatellite stable (MSS) patients is extremely low. In addition, preclinical studies have demonstrated that anti-Vascular endothelial growth factor (VEGF) agents, such as bevacizumab, can induce tumor vascular normalization and enhance antitumor immunity. Previous study indicated the combination of chemotherapy, anti-VEGF agents (bevacizumab) with immune checkpoint inhibitors may have promising clinical activity in RAS mutant, MSS refractory mCRC patients. Based on these evidences, we will explore the combination of CapeOx with bevacizumab and sintilimab (anti-PD-1 monoclonal antibody) in RAS mutant, MSS mCRC patients as first-line therapy. METHODS: This is a randomized, open-label, multicentric clinical trial. In the sintilimab arm, patients will receive sintilimab in combination with CapeOx and bevacizumab. In the control arm, patients will receive CapeOx and bevacizumab. This trial will recruit 494 patients from 20 centers and randomly (1:1) disseminated into two groups. The primary endpoint is the PFS. The secondary endpoints include overall survival, safety, ORR, and disease control rate. DISCUSSION: This study may provide new ideas for optimizing oncology treatment planning for RAS mutant, MSS mCRC patients in the first-line set. TRIAL REGISTRATION: This study is short for BBCAPX and has been registered at clinicaltrials.gov registry with identifier NCT05171660.

Hepatectomy Followed by Adjuvant Chemotherapy with 3-Month Capecitabine Plus Oxaliplatin for Colorectal Cancer Liver Metastases.

LESSONS LEARNED: Three-month adjuvant capecitabine plus oxaliplatin in combination (CAPOX) appeared to reduce recurrence, with mild toxicity in postcurative resection of colorectal cancer liver metastases (CLM). Recurrence in patients who underwent the 3-month adjuvant CAPOX after resection of CLM was most commonly at extrahepatic sites. BACKGROUND: The role of neoadjuvant and adjuvant chemotherapy in the management of initially resectable colorectal cancer liver metastases (CLM) is still unclear. We evaluated the feasibility of 3-month adjuvant treatment with capecitabine plus oxaliplatin in combination (CAPOX) for postcurative resection of CLM. METHODS: Patients received one cycle of capecitabine followed by four cycles of CAPOX as adjuvant chemotherapy after curative resection of CLM. Oral capecitabine was given as 1,000 mg/m2 twice daily for 2 weeks in a 3-week cycle, and CAPOX consisted of oral capecitabine plus oxaliplatin 130 mg/m2 on day 1 in a 3-week cycle. Primary endpoint was the completion rate of adjuvant chemotherapy. Secondary endpoints included recurrence-free survival (RFS), overall survival (OS), dose intensity, and safety. RESULTS: Twenty-eight patients were enrolled. Median age was 69.5 years, 54% of patients had synchronous metastases, and 29% were bilobar. Mean number of lesions resected was two, and mean size of the largest lesion was 31 mm. Among patients, 20 (71.4%; 95% confidence interval, 53.6%-89.3%) completed the protocol treatment and met its primary endpoint. The most common grade 3 or higher toxicity was neutropenia (29%). Five-year recurrence-free survival and overall survival were 65.2% and 87.2%, respectively. CONCLUSION: Three-month adjuvant treatment with CAPOX is tolerable and might be a promising strategy for postcurative resection of CLM.

A case of idiosyncratic liver injury after oxaliplatin-induced thrombocytopenia.

WHAT IS KNOWN AND OBJECTIVE: Oxaliplatin is a platinum drug used for treating digestive cancers that can lead to drug-induced thrombocytopenia (DITP). We report a case of oxaliplatin-induced anaphylaxis and DITP, complicated by idiosyncratic drug-induced liver injury (IDILI). CASE SUMMARY: A 46-year-old woman with rectal cancer developed anaphylaxis shortly after oxaliplatin administration (post-operative CapeOX), presenting with low platelet count (0.2 × 104 /µL) and elevated aspartate aminotransferase (1091 IU/L) and alanine aminotransferase (1010 IU/L) by day 10. Following 50 mg/d prednisolone administration from day 9, she left the hospital on day 36 after recovering. WHAT IS NEW AND CONCLUSION: This is the first case report of oxaliplatin-induced IDILI and its effective treatment with steroids.

Intermittent Withdrawal of Oxaliplatin for Alleviating Neurotoxicity during Oxaliplatin-Based Chemotherapy for Japanese Patients with Inoperable or Metastatic Colorectal Cancer: A Phase 2 Multicenter Study.

Oxaliplatin-based chemotherapy is a well-established regimen for patients with inoperable and metastatic colorectal cancer. However, one of the major limitations of oxaliplatin-based chemotherapy is sensory neuropathy. It was previously reported that introduction of intermittent oxaliplatin treatment to an oxaliplatin-based regimen has a significant benefit on efficacy or safety. Here, we prospectively assessed whether efficacy and safety of first-line chemotherapy for advanced colorectal cancer are achieved by introduction of withdrawal of oxaliplatin treatment for a certain period (intermittent oxaliplatin treatment). The primary endpoint of the present study is to assess the progression free survival time on patients treated with chemotherapy (mFOLFOX6 (levofolinate, 5-fluorouracil and oxaliplatin combination therapy) plus bevacizumab or CapeOX (oxaliplatin and capecitabine combination therapy) plus bevacizumab) with intermittent oxaliplatin treatment. Bevacizumab is a humanized anti-vascular endothelial growth factor antibody. Median progression-free survival by the mFOLFOX6 plus bevacizumab with intermittent oxaliplatin treatment or the CapeOX plus bevacizumab with intermittent oxaliplatin treatment were 10.6 months (95% confidential interval [CI], 8.3-13.4 months) or 8.0 months (95% CI, 4.2-16.8 months), respectively. Overall response rate by the mFOLFOX6 plus bevacizumab with intermittent oxaliplatin treatment or CapeOX plus bevacizumab with intermittent oxaliplatin treatment was 55.1% or 42.1%, respectively. Grade 3 or 4 neuropathy was observed in 4.1% or 10.5% of patients treated with mFOLFOX6 plus bevacizumab with intermittent oxaliplatin treatment or CapeOX plus bevacizumab with intermittent oxaliplatin treatment, respectively. Introduction of intermittent oxaliplatin treatment has improved severe neuropathy in mFOLFOX6 plus bevacizumab regimen without reducing treatment efficacy.

Oxaliplatin plus S-1 or capecitabine as neoadjuvant or adjuvant chemotherapy for locally advanced gastric cancer with D2 lymphadenectomy: 5-year follow-up results of a phase II-III randomized trial.

OBJECTIVE: To compare the effect of neoadjuvant chemotherapy (NACT) with adjuvant chemotherapy (ACT) using oxaliplatin plus S-1 (SOX) or capecitabine (CapeOX) on gastric cancer patients with D2 lymphadenectomy. METHODS: This was a two-by-two factorial randomized phase II-III trial, and registered on ISRCTN registry (No. ISRCTN12206108). Locally advanced gastric cancer patients were randomized to neoadjuvant SOX, neoadjuvant CapeOX, adjuvant SOX, or adjuvant CapeOX arms. Primary analysis was performed on an intention-to-treat (ITT) basis using overall survival (OS) as primary endpoint. RESULTS: This trial started in September 2011 and closed in December 2012 with 100 patients enrolled. Treatment completion rate was 56%, 52%, 38% and 30% in the four arms, respectively. NACT group had fewer dropouts due to unacceptable toxicity (P=0.042). Surgical complication rate did not differ by the four groups (P=0.986). No survival significant difference was found comparing NACT with ACT (P=0.664; 5-year-OS: 70% vs. 74% respectively), nor between the SOX and CapeOX groups (P=0.252; 5-year-OS: 78% vs. 66% respectively). Subgroup analysis showed SOX significantly improved survival in patients with diffuse type (P=0.048). CONCLUSIONS: No significant survival difference was found between NACT and ACT. SOX and CapeOX had good safety and efficacy as neoadjuvant regimens. Diffuse type patients may survive longer due to SOX.

Neoadjuvant CapeOx therapy followed by sphincter-preserving surgery for lower rectal cancer.

PURPOSE: This retrospective study investigates the safety of neoadjuvant chemotherapy with oxaliplatin capecitabine (CapeOx), followed by laparoscopic surgery, for lower rectal cancer, and its efficacy in preserving the sphincter. METHODS: Ten patients with diagnosed lower rectal cancer received three or four cycles of neoadjuvant CapeOx chemotherapy, prior to undergoing low anterior resection or intersphincteric resection, with total mesorectal excision. The primary outcomes were R0 resection and the rate of sphincter preservation. RESULTS: Nine patients completed CapeOx as scheduled and a partial response was achieved in four; thus, the overall response rate was 40% (n = 4/10). After surgical intervention, 80% of tumors displayed downstaging. Postoperative anastomosis leakage developed in one patient. The distance from the anal verge to the tumor increased by 60% (median 1.5 cm) after CapeOx treatment. The anal sphincter was preserved in all patients and all pathological distal and radial margins were negative (R0 resections). A pathological complete response was achieved in one patient. CONCLUSIONS: Neoadjuvant CapeOx chemotherapy is a promising approach, because it extended the distance from the anus to the tumor. Subsequent laparoscopic intervention for advanced lower rectal cancer could allow for safe preservation of the sphincter.

Risk Factors Exacerbating Hand-Foot Skin Reaction Induced by Capecitabine plus Oxaliplatin with or without Bevacizumab Therapy.

BACKGROUND: Capecitabine plus oxaliplatin (CapeOx) ± bevacizumab therapy is associated with a high incidence of hand-foot skin reaction (HFSR), hindering treatment. However, timing of onset and risk factors remain unclear. OBJECTIVE: This study examined the development of HFSR and risk factors for its exacerbation to a serious condition in CapeOx ± bevacizumab therapy. METHODS: We retrospectively examined patients with colorectal cancer receiving CapeOx ± bevacizumab therapy between October 1, 2009, and March 31, 2012. The observation period was defined as lasting until completion of 8 cycles. The relationship between cumulative dose of capecitabine and cumulative proportion of patients developing HFSR was evaluated by Kaplan-Meier methods. Risk factors for exacerbation of HFSR to a serious condition were assessed by multiple logistic regression. RESULTS: Data for 203 patients were analyzed. For patients treated at cumulative capecitabine doses of 100 000 mg/m(2) and 200 000 mg/m(2), Grade 1 HFSR occurred in ≥80% and ≥90%, respectively, and moderate-to-severe HFSR (Grade 2+) occurred in ≥10% and ≥20%, respectively. Multivariate analysis showed significant associations with diabetes (odds ratio [OR] = 4.79; 95% confidence interval [CI] = 1.86-12.34; P = 0.001), concomitant use of bevacizumab (OR = 6.01; 95% CI = 2.20-16.41; P = 0.001), history of fluorinated pyrimidine administration (OR = 2.42; 95% CI = 1.10-5.33; P = 0.027), and early onset (within 21 days) of Grade 1 HFSR (OR = 3.78; 95% CI = 1.64-8.70; P = 0.001). CONCLUSIONS: HFSR in CapeOx therapy is a cumulative toxicity and risk of exacerbation to a serious condition increases with diabetes, concomitant use of bevacizumab, history of fluorinated pyrimidine administration, and onset of Grade 1 HFSR within 21 days.

Effect of electroacupuncture of "Zusanli" (ST36) combined with capeOX on apoptosis and ferroptosis in nude mice with colorectal cancer. / 电针"足三里"联合capeOXæ–¹æ¡ˆå¯¹ç»“ç›´è‚ ç™Œè£¸é¼ è‚¿ç˜¤ç»†èƒžå‡‹äº¡å’Œé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To investigate the impact of combined treatment of colorectal cancer (CRC) with electroacupuncture (EA) and capeOX (combined administration of fluorouracil, oxaliplatin and capecitabine) on the tumor volume, weight, spleen coefficient, apoptosis and ferroptosis of tumor tissue, and liver and kidney functions in nude mice with CRC, so as to explore its mechanisms underlying inhibiting CRC and alleviating toxic reactions of capeOX. METHODS: Female Balb/c nude mice were randomly assigned to 3 groups：model, capeOX, and EA+capeOX, with 8 nude mice in each group. The CRC model was established by subcutaneous injection of colon cancer cells at the right inguinal region. Nude mice of the capeOX group received intraperitoneal injection of oxaliplatin for 1 day and gavage of capecitabine from day 2 to day 7. EA (1 mA, 2 Hz/100 Hz) was applied to bilateral "Zusanli" (ST36) for 20 min, once daily for 7 days. During the interven-tion, the tumor volume and weight were measured every day, and at the end of intervention, the weight of the tumor tissue and spleen were measured, with tumor volume difference and spleen coefficient calculated. The proportion of apoptotic cells was measured by flow cytometry, and the contents of serum malondialdehyde (MDA), alanine aninotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were detected using ELISA. The expression level of glutathione peroxidase 4 (GPX4, a key regulator for ferroptosis) protein of the tumor tissue was determined using Western blot. RESULTS: Compared to the model group, both the capeOX group and EA+capeOX group showed a decrease in the tumor volume (on day 3 and 4 in the capeOX group, and from day 2 to 7 in the EA+capeOX group) and body weight (P<0.05, on day 3 to 7 in the EA+capeOX group and on day 2 to 7 in the capeOX group), being evidently lower in the tumor volume on day 7 in the EA+capeOX than in the capeOX group (P<0.05), and evidently higher in the body weight on day 6 and 7 in the EA+capeOX group than in the capeOX group (P<0.05). In comparison with the model group, the tumor volume difference, tumor weight and spleen coefficient in both capeOX and EA+capeOX groups were significantly decreased (P<0.05), and MDA content in EA+capeOX group was significantly decreased (P<0.05), while the contents of ALT, BUN and Cr in the capeOX group, the proportion of apoptotic cells in both capeOX and EA+capeOX groups, and the GPX4 expression level in the EA+capeOX group were all significantly increased (P<0.05). The tumor volume difference, tumor weight, and contents of MDA, ALT, AST, BUN and Cr in the EA+capeOX group were markedly lower than in the capeOX group (P<0.05), while the spleen coefficient, proportion of apoptotic cells and GPX4 expression level in the EA+capeOX group were markedly higher than those in the capeOX group (P<0.05). CONCLUSIONS: EA of ST36 can enhance the effect of capeOX in inhibiting colorectal cancer growth in nude mice with CRC, which may be related with its functions in promoting tumor cell apoptosis, inhibiting ferroptosis, and modulating immune tolerance. In addition, EA can lower the side effects of capeOX in hematopoietic and immune, liver, and kidney functions.

Study on prediction of early adverse events by CapeOX therapy in patients with colorectal cancer.

CapeOX is a regimen used as postoperative adjuvant chemotherapy for the treatment of advanced recurrent colorectal cancer. If early adverse events occur, treatment may not progress as planned and further dose reduction may be necessary. In this study, we investigated whether pre-treatment medical records could be used to predict adverse events in order to prevent adverse events caused by CapeOX treatment. The 178 patients were classified into two groups (97 in the adverse event positive group and 81 in the adverse event-negative group) based on withdrawal or postponement of four or fewer courses. In univariate analysis, age, height, weight, body surface area (BSA), creatinine clearance, muscle mass, and lean body mass were associated with early adverse events (P<0.05). The area under the receiver operating characteristic curve obtained by Stepwise logistic regression analysis using the Akaike information criterion method was 0.832. For nested k-fold cross validation, the accuracy rates of the support vector machine, random forest, and logistic regression algorithms were 0.71, 0.70, and 0.75, respectively. The results of the present study suggest that a logistic regression prediction model may be useful in predicting early adverse events caused by CapeOX therapy in patients with colorectal cancer. J. Med. Invest. 71 : 141-147, February, 2024.

Cancer concepts and principles: primer for the interventional oncologist-part II.

This is the second of a two-part overview of the fundamentals of oncology for interventional radiologists. The first part focused on clinical trials, basic statistics, assessment of response, and overall concepts in oncology. This second part aims to review the methods of tumor characterization; principles of the oncology specialties, including medical, surgical, radiation, and interventional oncology; and current treatment paradigms for the most common cancers encountered in interventional oncology, along with the levels of evidence that guide these treatments.

Hepatoid adenocarcinoma of the stomach effectively treated with capecitabine with oxaliplatin as adjuvant chemotherapy: A case report and literature review.

INTRODUCTION: Hepatoid adenocarcinoma of the stomach (HAS) is an alpha-fetoprotein (AFP)-producing gastric carcinoma (GC) with a hepatocellular carcinoma-like histology. HAS is a relatively rare type of GC, with liver metastases being more common than peritoneal dissemination in the recurrent form, and the poor prognosis. PRESENTATION OF CASE: We present the case of a 70-year-old patient who underwent distal gastrectomy for GC and immunohistologically diagnosed as HAS. The patient had an intravenous tumor thrombus at the proximal margin of the resected stomach. Owing to the low possibility of radical resection and high probability of liver metastatic recurrence, capecitabine with oxaliplatin (CapeOX) was started as adjuvant chemotherapy (AC). After three courses of CapeOX, oxaliplatin was discontinued due to adverse events (peripheral neuropathy, grade3) and capecitabine alone was continued for 3 years postoperatively. Six years after surgery, no local recurrence or distant metastasis was detected on imaging studies. DISCUSSION: There is no established standard treatment for HAS. Recently, some studies have reported the efficacy of antimetabolites or platinum-based drugs as AC regimens. We thus decided to start a regimen consisting of a combination of antimetabolites and a platinum, i.e., CapeOX, which proved efficacious. CONCLUSION: CapeOX or capecitabine may be effective as AC for treating HAS.

Association between the Co-administration of Histamine H2 Receptor Antagonists and the Effectiveness of Capecitabine in Patients with Colorectal Cancer: Propensity Score Analysis.

Background: The association between the effectiveness of capecitabine and the concomitant administration of gastric acid suppressants remains controversial. We aimed to clarify whether the effectiveness of capecitabine is affected by the co-administration of histamine H2 receptor antagonists (H2RAs) in early-stage colorectal cancer (CRC) patients using real-world data. Methods: This multicenter, retrospective, observational study included consecutive patients with stage II-III CRC who received either capecitabine monotherapy or the CapeOX regimen (capecitabine and oxaliplatin) as adjuvant therapy between January 2009 and December 2014 in Japan. Relapse-free survival (RFS) and overall survival were estimated using the Kaplan-Meier method. Additionally, multivariable Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting analyses were performed. Results: In total, 552 patients were included in this study, of which 30 were co-administered H2RAs. RFS at five years was 76.7% (95% confidence interval [CI]: 57.2-88.1%) and 79.8% (95% CI: 76.0-83.0%) in the H2RA and non-H2RA groups, respectively. Multivariable Cox proportional hazards model and propensity score-adjusted analyses showed that the co-administration of H2RAs was associated with a poor RFS among those receiving capecitabine monotherapy (hazard ratio [HR], 2.01; 95% CI: 0.86-4.70 and HR, 1.81; 95% CI: 0.77-4.22, respectively). In contrast, these results were inconsistent with the group receiving the CapeOX regimen. Conclusions: The study findings suggest that the co-administration of H2RAs may not reduce the effectiveness of capecitabine therapy in patients with early-stage CRC. To confirm this relationship, a prospective study with a pharmacokinetic approach is needed.

Preoperative Nutritional Status Contributes to the Development of Neutropenia Event in Patients With Gastric Cancer Receiving CAPEOX Adjuvant Chemotherapy.

Purpose: The aim of this study is to evaluate the risk factors for ≥ grade 3 neutropenia in gastric cancer patients receiving postoperative adjuvant chemotherapy. Methods: This is a retrospective study from a single tertiary referral hospital. Patients diagnosed with gastric cancer who met the inclusion criteria were included in this study. Baseline and clinicopathological characteristics of the patients were collected. Patients were followed-up for 12 months and the incidence of neutropenia were recorded. Factors associated with neutropenia of chemotherapy in cycle 1 were investigated. Results: A total of 202 patients with gastric cancer were included. All patients received oxaliplatin plus oral capecitabine (CAPEOX) as the adjuvant chemotherapy. The incidence of ≥ grade 3 neutropenia is 11.9% (24/202) in cycle 1 among all patients. In multivariate analysis, independent risk factors for ≥ grade 3 neutropenia were serum prealbumin level (p = 0.041), prognostic nutritional index (PNI) (p = 0.049) and pre-cycle neutrophil count (p = 0.007). Conclusions: Our findings for the first time showed that nutritional parameter as prealbumin level and PNI are independent risk factors for neutropenia in gastric cancer patients receiving adjuvant chemotherapy. This may provide evidence for further investigation on prophylaxis use of granulocyte colony-stimulating factor in selected high-risk patients to prevent sever neutropenia in cycle 1 of adjuvant chemotherapy.

Feasibility Study of a Modified XELOX Adjuvant Chemotherapy for High-Recurrence Risk Patients With Operated Stage III Colon Cancer.

BACKGROUND: Our previous study reported the favorable efficacy and good tolerance associated with a modified XELOX adjuvant chemotherapy with eight cycles of capecitabine and six cycles of oxaliplatin for operated stage III colon cancer. The current study aimed to confirm the feasibility of modified XELOX chemotherapy for treating specific high-risk (T4, N2, or both) stage III colon cancer. METHODS: We selected 142 consecutive patients with high-risk stage III colon cancer who received colon tumor resection followed by modified XELOX or standard full-cycle XELOX chemotherapy from November 2007 to June 2016 at Sun Yat-sen University Cancer Center. Disease-free survival (DFS), overall survival (OS), and adverse events of patients treated with the two chemotherapy regimens were compared. RESULTS: Seventy-four (52.1%) patients received standard XELOX chemotherapy, and 68 (47.8%) received modified XELOX chemotherapy. Neurotoxicity was the most common adverse event in 99 (69.7%) patients. Grade 2-3 neurotoxicity, grade 2-4 thrombocytopenia and grade 3-4 leucopenia were the major severe adverse events related to the decision to treat patients with modified XELOX chemotherapy. After a median follow-up of 69 months, the modified XELOX group presented a comparable 5-year DFS rate (79.0 vs. 80.3%, P = 0.891) and 5-year OS rate (93.8 vs. 87.8%, P = 0.446) as those in the standard XELOX group. Univariate survival analysis indicated that poor tumor differentiation (HR: 2.381, 95% CI: 1.141-4.968, P = 0.021) was the only significant risk factor for DFS, but no significant prognostic factor was identified for OS. CONCLUSIONS: The modified XELOX adjuvant chemotherapy presented a comparable oncologic efficacy as standard XELOX chemotherapy for high-risk stage III colon cancer. The modified XELOX adjuvant chemotherapy could be an alternative treatment for patients suffering severe adverse events, especially severe neurotoxicity.

Adjuvant Chemotherapy after Neoadjuvant Chemotherapy and Long-term Outcomes of CAPOX Plus Bevacizumab Followed by TME for High-risk Localized Rectal Cancer.

OBJECTIVES: We previously reported the feasibility of neoadjuvant capecitabine and oxaliplatin plus bevacizumab as a treatment for locally advanced rectal cancer (UMIN000003219). The aim of this study is to investigate the prognostic relevance of neoadjuvant chemotherapy followed by total mesorectal resection (TME). METHODS: Twenty-five patients of our prior multicenter prospective study of neoadjuvant chemotherapy followed by TME enrolled to this study. We analyzed the adjuvant chemotherapy regimen, and the duration between surgery and initial chemotherapy treatment. Five-year progression-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS: Among survivors, the median follow-up time was 66 months. Recurrence occurred in six patients, all of whom had suboptimal tumor regression after neoadjuvant chemotherapy. Five patients died from other causes. The rate of local recurrence and distant metastasis was 17.4% and 8.7%, respectively. Five-year progression-free survival was 70.0%, and 5 year overall survival was 84.0%. CONCLUSIONS: We report the long-term survival of patients who received neoadjuvant chemotherapy without radiation followed by TME, revealing a generally favorable prognosis.

An Observational Study of Team Management Approach for CapeOX Therapy in Patients with Advanced and Recurrent Colorectal Cancer: SMILE Study (The Study of Metastatic colorectal cancer to investigate the Impact of Learning Effect).

OBJECTIVES: In recent years, CapeOX therapy for patients with colorectal cancer is widely used. We previously reported that a multidisciplinary approach decreases the worsening of adverse events and increases patient satisfaction. In this study, we conducted a multicenter, prospective, observational study to evaluate the incidence of adverse events, health-related quality of life (HRQOL) of the patient, and efficacy of a management (intervention) according to the support system (SMILE study). METHODS: As the interventional method, the following more than one method was carried out in each institute, 1: support with telephone, 2: dosing instruction by a pharmacist, 3: skin care instruction by a nurse, and 4: patient instruction by a doctor. The primary endpoint was the incidence of hand-foot syndrome (HFS) of more than grade 2. The secondary endpoint was the HRQOL evaluation and efficacy. The questionnaire (HADS) was administered before the start of the chemotherapy and in 1, 2, 4, 5, and 8 courses to evaluate quality of life (QOL). RESULTS: From April 2011 to September 2012, 80 patients were enrolled from 14 sites, and all patients were the subjects of analysis. The demographic background was as follows: man/woman: 46/34, age median: 63 (36-75), and management interventional method 1/2/3/4: 36/68/73/78. The overall percentage of HFS that exceeded grade 2 within 6 months was 16.3%. It was 11.1% with the telephone support group and 20.5% without the telephone support group (p = 0.26). CONCLUSIONS: A multi-professional telephone support may reduce the deterioration of HFS. Further study which includes larger cohort is needed in the future.

Gut microbiome associated with chemotherapy-induced diarrhea from the CapeOX regimen as adjuvant chemotherapy in resected stage III colorectal cancer.

BACKGROUND: Chemotherapy induced diarrhea (CID) is a common side effect in patients receiving chemotherapy for cancer. The aim of our study was to explore the association between gut microorganisms and CID from the CapeOX regimen in resected stage III colorectal cancer (CRC) patients. RESULTS: After screening and identification, 17 stool samples were collected from resected stage III CRC patients undergoing the CapeOX regimen. Bacterial 16S ribosomal RNA genes was sequenced, and a bioinformatics analysis was executed to screen for the distinctive gut microbiome and the functional metabolism associated with CID due to the CapeOX regimen. The gut microbial community richness and community diversity were lower in CID (p < 0.05 vs control group). Klebsiella pneumoniae was the most predominant species (31.22%) among the gut microbiome in CRC patients with CID. There were 75 microorganisms with statistically significant differences at the species level between the CRC patients with and without CID (LDA, linear discriminant analysis score > 2), and there were 23 pathways that the differential microorganisms might be involved in. CONCLUSIONS: The gut microbial community structure and diversity have changed in CRC patients with CID. It may provide novel insights into the prevention and treatment of CID.

Randomized phase II trial of the prophylactic use of celecoxib for the prevention of oxaliplatin-related peripheral vascular pain in Capeox (YCOG1205).

PURPOSE: Capeox is widely used as an adjuvant chemotherapy regimen of colorectal cancer that does not require central vein catheter insertion. However, oxaliplatin-related vascular pain with peripheral administration is a major adverse event. We assessed the preventive effect of Celecoxib on oxaliplatin-related vascular pain. METHODS: A multicenter study of the Yokohama Clinical Oncology Group (YCOG) in Japan. This study was an open label, randomized non-comparative phase II study between Capeox without Celecoxib (C+ Group) and with it (C- group). The primary endpoint was the appearance frequency of grade ≥ 2 vascular pain according to the Verbal Rating Scale (VRS). RESULTS: Between October 2012 and February 2014, 81 patients were recruited to this study and randomly divided into 2 groups: 38 patients in the C- group and 39 patients in the C+ group. Four cases were excluded at the analysis stage because they had not received the allocated intervention. The rate of grade ≥ 2 vascular pain was 55.3% in the C- group and 53.8% in the C+ group (p = 1.000). CONCLUSIONS: Celecoxib was unable to prevent oxaliplatin-related vascular pain in this study. However, it may be able to decrease the vascular pain that patients already have.

Treatment of Gastric and Gastroesophageal Cancer Patients with Hemodialysis by CapeOX.

Two patients underwent hemodialysis. Case 1 with stage IV gastric cancer was treated with reduced doses of capecitabine (1,000 mg/m2/day, days 1 to 14) and oxaliplatin (65 mg/m2, day 1). Although grade 1 thrombocytopenia occurred in the first cycle, grade 3 thrombocytopenia developed in the second cycle because of increasing dosage. After the dosage was reduced, chemotherapy was continued safely. Case 2 with stage IA gastroesophageal cancer was treated with radiotherapy followed by chemotherapy. Treatment with the same dose of CapeOX therapy as in case 1 resulted in no severe toxicity. We conclude that a half-dose of the CapeOX regimen is safe for gastric cancer patients undergoing hemodialysis.