CAPOX Regimen Research Articles

Adjuvant and perioperative neoadjuvant therapy for colorectal cancer

Colorectal cancer is one of the most common malignant tumors in the world, threatening human health. The treatment strategy of stage II and stage III colorectal cancer has changed from surgery alone to multidisciplinary mode emphasizing perioperative treatment. The indication of adjuvant chemotherapy for stage II colon cancer is still defined by high-risk factors, but only microsatellite status and BRAF gene mutation can help predict efficacy of chemotherapy. Combined chemotherapy is the main adjuvant therapy for stage III colon cancer. The recommended course of adjuvant chemotherapy is 6 months. Based on the results of the IDEA study, the three-month CapeOX regimen (oxaliplatin and capecitabine) is recommended for the treatment of patients with T1-3 and N1 tumors. Neoadjuvant chemotherapy for locally advanced colon cancer is still in the exploratory stage of clinical trials. The difference between the treatment of rectal cancer and colon cancer lies in the application of radiotherapy. Chemoradiotherapy combined with TME (total mesorectal excision) surgery and adjuvant chemotherapy has become the standard treatment for locally advanced rectal cancer. Nowadays, the research hotspots in neoadjuvant therapy of rectal cancer include neoadjuvant chemotherapy and total neoadjuvant therapy (TNT). This article will review the progress of perioperative treatment for colorectal cancer.

A retrospective study of a dexamethasone-sparing strategy of preventing acute and delayed emesis caused by CapeOx regimen with aprepitant for colorectal cancer.

632 Background: CapeOx therapy which is combination with oxaliplatin (L-OHP) and capecitabine is one of the standard treatments for first line chemotherapy for unresectable colorectal cancer, or for postoperative adjuvant chemotherapy for stage III colon cancer. L-OHP-based regimen is classified as moderately emetogenic chemotherapy. In the SENRI trial which we previously conducted as phase III trial, aprepitant, an NK-1 antagonist, showed the efficacy for prevention of emesis against L-OHP. On the other hand, even when in highly emetogenic chemotherapy, it is reported that dexamethasone after day 2 could be spared. Methods: We retrospectively reviewed chemo-naive 94 patients with colorectal cancer who underwent CapeOx therapy at our institution from April 2012 to March 2017. We assessed the relationship between emesis during the first cycle of CapeOx (day1-5) and the use of dexamethasone on day 2-3. Results: 10 patients underwent CapeOx plus bevacizumab, and 84 underwent CapeOx. All patients received 5-HT3 receptor antagonist (palonosetron: 87, granisetron: 7). 50 patients received aprepitant on days 1-3 and dexamethasone on day 1 (APR+D1 group). 22 patients received aprepitant on days 1-3 and dexamethasone on days 1-3 (APR+D3 group). 15 were dexamethasone on days 1-3 without aprepitant (D3 group), and 7 were dexamethasone only on day 1 without aprepitant (D1 group). Acute complete response (CR; no vomiting and no rescue anti-emetics) rates were 100% in any groups. Delayed CR rate was 56% in APR+D1 group, 86% in APR+D3 group, 53% in D3 group, and 29% in D1 group, respectively. In multivariate linear regression with aprepitant, there was a significant difference in presence of dexamethasone (p = 0.028). Conclusions: Acute emesis could be prevented by even only 1-day administration of dexamethasone when combined with the triplet prophylactics. However, in order to sufficiently prevent delayed emesis induced by L-OHP, it was suggested that addition of DEX on days 2 and 3 might be better.

CapeOX perioperative chemotherapy versus postoperative chemotherapy for locally advanced resectable colon cancer: protocol for a two-period randomised controlled phase III trial

IntroductionAdjuvant chemotherapy with the CapeOX regimen is now widely used for treating colorectal cancer. However, prior studies have demonstrated better efficacy of pre-operative/neoadjuvant chemotherapy without increase of safety risks.Methods and...

The Optimal Duration of Adjuvant Therapy for Stage III Colon Cancer: the European Perspective

The International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration was created to pool data from different studies worldwide in order to assess whether a shorter duration of adjuvant treatment in colon cancer could maintain the expected benefit while reducing toxicity. The results of the IDEA trials were clinically relevant. They confirmed a two- to sixfold reduction in neurotoxicity for the shorter duration across trials. Overall, the 3-year disease-free survival was very similar: only 0.9% lower for the 3months group. However, the results were partially unexpected, because they revealed a difference among chemotherapy regimens (CAPOX better than FOLFOX) and risk groups within stage III. The similar outcome between 3 and 6months of CAPOX coupled with the substantial reduction in toxicity makes us use the CAPOX regimen for 3months for most stage III patients. An exception to this general rule is the patient with very high risk, i.e., either T4N1b-T4anyN2 or anyTN2b where we use 6months of CAPOX. Our take from the trial results is also that FOLFOX should never be given for 3months and preferably not used at all in the adjuvant setting. The conduction of the IDEA enterprise was truly global. The European contribution was major with three fourths of patients enrolled in the four European trials. Herein, we review the results of the "3 versus 6" trials and the literature regarding the interpretation of the collected data in Europe and in the rest of the world.

SCOT: a comparison of cost-effectiveness from a large randomised phase III trial of two durations of adjuvant Oxaliplatin combination chemotherapy for colorectal cancer

BACKGROUNDThe Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer.METHODSIn total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3–8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan–Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken.RESULTSThe 3 M arm is less costly (-£4881; 95% CI: -£6269; -£3492) and entails (non-significant) QALY gains (0.08; 95% CI: −0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant).CONCLUSIONSOverall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care.

Noninferiority of three months versus six months of oxaliplatin-based adjuvant chemotherapy for resected colon cancer. How should IDEA findings affect clinical practice?

The eagerly awaited results of the multi-continental International Duration Evaluation of Adjuvant Chemotherapy (IDEA) project have recently been presented at major oncological meetings. The 3-year disease-free survival (DFS) was presented for 12,834 Stage III colon cancer patients in a pooled analysis of 6 individual noninferiority phase III randomized trials, all investigating three versus six months of oxaliplatin-based adjuvant therapy. Noninferiority (NI) could not be demonstrated for the whole population as the DFS hazard ratio (HR) of 1.07 with its 95% CI of 1.00-1.15 crossed the postulated NI boundary of 1.12. However, there was an expected reduction in the incidence of specific side effects with the three months treatment. NI could be demonstrated for the T3N1 subgroup (∼60% of patients, HR for DFS 1.01, 95% CI 0.90-1.12). Moreover, NI was also declared for the subgroup treated with the CAPOX regimen (capecitabine plus oxaliplatin, ∼40% of patients), but the CAPOX choice was physician-based and not subject to randomization. Overall, the IDEA results indicate that three months of therapy might be adequate for most of Stage III tumors; however, a small subset of these patients still have high risk of recurrence and death with short treatment duration. Precise predictors of benefit need to be identified, nonetheless tumor-intrinsic factors, such as tumor stage, might currently be considered as useful tools to inform the decision-making process.

SURGICAL TREATMENT OF REGIONAL RECURRENCE FROM GASTRIC CANCER AFTER MULTIMODAL TREATMENT WITH NEOADJUVANT CHEMORADIOTHERAPY (A CASE REPORT)

Background. Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related death worldwide. Despite many advances in the diagnosis and treatment of gastric cancer, the overall five-year survival rate does not exceed 25–30 %, and distant metastases and loco-regional recurrence develop in more than 50 % of patients. Disease recurrence is not only associated with the presence of tumor micro-metastases at the time of surgery, but also with dissemination of tumor cells during mobilization of the stomach or lymph node dissection. Even after performing radical surgery, the prognosis remains extremely unfavorable. No standardized methods of treatment for isolated loco-regional recurrence have been developed yet. Cases of successful treatment of distant metastases and regional recurrence are sporadic. Case report. We present the case of a 75-year-old patient with histologically proven well-differentiated tubular adenocarcinoma of the stomach. The patient underwent neoadjuvant chemoradiation therapy (total radiotherapy dose was 45 Gy, modified Capox regimen) followed by gastrectomy and D2lymph node dissection. The control examination revealed an isolated regional recurrence of gastric cancer. It was decided to perform surgical treatment for isolated regional gastric cancer recurrence. Conclusion. There is no standardized approach to the treatment of regional recurrence of gastric cancer. Surgical treatment in such cases is a method of choice, especially for patients who previously received neoadjuvant chemoradiotherapy. According to the worldwide literature, the median survival of such patients does not exceed a few months. The key point that determines the effectiveness of neoadjuvant therapy is the achievement of complete or partial pathological response to therapy, thus demonstrating improved survival compared to surgery alone. Therefore, it is extremely important to search for immunohistochemical and molecular genetic markers for predicting tumor response to neoadjuvant therapy in order to administer it for only potential responders.

720P - Inoperable carcinoma gallbladder: Comparison of two palliative chemotherapy regimens (gemcitabine-platinum versus CAPEOX)

Background: Cancer of the gall bladder (CaGB) constitutes one of the ten commonest cancers in women in north India. Palliative chemotherapy is indicated for the advanced stage, inoperable patient in good performance status (PS). There is no standard-of-care regimen for this disease. We prospectively evaluated the efficacy & safety of GEMPLAT v/s CAPEOX chemotherapy in this cohort of patients. Methods: Fifty chemo-naive, newly diagnosed patients (25 in each arm) of inoperable CA GB, in good PS (0, I, II) were included. Patients were randomised to receive either GEMPLAT or CAPOX. Primary end point was response rates (RR) & progression free survival (PFS); secondary end point: Overall survival (OS), toxicity & quality of life (QOL). Response assessment was done after every two cycles using by the RECIST 1.1 criteria. QOL was assessed every two cycles. Results: Thirty one females & 19 males, mean age of 45.7 years (range 32 to 69) were included. There were no CRs in either arm. Partial response (PR) & stable disease (SD) was seen in 6 (24%) & 8 (32%) patients, respectively, in GEMPLAT arm; and 2 (8%) and 5 (20%) achieved PR and SD, respectively in CAPEOX group. Overall response rate (ORR) was 24% & 8%, respectively, for GEMPLAT & CAPOX. The median OS in GEMPLAT arm was 9.9 months versus 2.6 moths in CAPOX. The median PFS was higher in GEMPLAT group (7.6 months) as compared to CAPOX group (1.5 months). Grade 3/4 anemia & neutropenia occurred in 3 (12%) & 2 (8%) patients in the GEMPLAT arm, respectively with no grade 3/4 hematological toxicities in CAPOX arm. Five (20%) patients developed grade 3/4 transaminitis on GEMPLAT. One (4%) patients in CAPOX arm developed sensory neuropathy and 3 (12%) have grade 3/4 skin toxicity. Conclusions: In our study, the GEMPLAT regimen showed higher RR, OS and PFS as compared to CAPOX. QOL was better in the GEMPLAT arm. CAPOX regimen was better tolerated and less toxic. The main toxicity of GEMPLAT was haematological & hepatic while that of CAPEOX was dermatological. We conclude that GEMPLAT should be the standard-of-care first line palliative chemotherapy regimen for inoperable CaGB patients in good PS. Larger, multi-centre studies are needed to confirm our findings and to compare CAPOX/other regimens with GEMPLAT. Legal entity responsible for the study: Prof. Dr. Hemant Malhotra Funding: None Disclosure: All authors have declared no conflicts of interest.

Proton pump inhibitors increase the chemosensitivity of patients with advanced colorectal cancer.

Changes in pH can alter the uptake of chemotherapy drugs. Proton pump inhibitors (PPIs) may therefore increase the chemosensitivity of cancer cells and cytotoxicity of chemotherapeutic drugs by increasing their uptake. We investigated the chemosensitizing potential of PPIs in colorectal cancer (CRC). Our in vitro data show that the PPI pantoprazole increases the chemosensitivity of CRC HT29 and RKO cells to fluorouracil (5-FU). Our in vivo data demonstrate that pantoprazole also increases the ability of 5-FU to inhibit CRC tumor growth in mice. Importantly, a retrospective clinical study of CRC patients receiving the FOLFOX or CapeOx regimen indicates that PPIs increase the chemosensitivity of CRC patients. Patients who received the FOLFOX regimen with a PPI had better overall survival (OS) and progression-free survival (PFS) than patients who did not receive a PPI during FOLFOX chemotherapy. The incidence of nausea and vomiting was also lower in patients receiving a PPI with FOLFOX or CapeOx than in those who did not receive PPI. These results indicate that PPIs may be successfully incorporated into the FOLFOX regimen to increase the chemotherapeutic effect for CRC patients.

Additional chemotherapy and salvage surgery for poor response to chemoradiotherapy in rectal cancers.

A proportion of locally advanced rectal cancer patients who receive neoadjuvant chemoradiotherapy (NACRT) are still unresectable. This study was undertaken to assess the outcomes of giving additional chemotherapy to rectal cancer patients with unresectable disease after NACRT. Patients with poor response to NACRT where mesorectal fascia was still involved on MRI and R0 resection was doubtful, received additional four cycles of chemotherapy with either CAPOX or FOLFIRINOX regimen, and the response was reevaluated with MRI and reassessed for surgical resection. Between June 2012 and December 2014, 50 patients received additional chemotherapy with CAPOX regime (19%, 38%) or FOLFIRINOX (31%, 62%) after CRT. Median number of chemotherapy cycles received was four (range 2-8 cycles). Overall 34 (68%) patients underwent exploration and 31 (62%) underwent R0 resection. The median time to surgery following chemoradiation was 5 months (range 3-18 months). Complete pathological response was seen in seven (22%) patients. Patients with poor response to NACRT may be further downstaged using additional chemotherapy so as to achieve R0 resection in 62% of cases.

Randomized Phase III Study to Assess Efficacy and Safety of Adjuvant CAPOX with or without Bevacizumab in Patients after Resection of Colorectal Liver Metastases: HEPATICA study

Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF). Recurrence after resection of colorectal liver metastases (CRLMs), presumably caused by VEGF-mediated outgrowth of micrometastases, might decrease when VEGF is inhibited. This study examines the efficacy and safety of adding bevacizumab to an adjuvant regimen of CAPOX in patients undergoing radical resection for their CRLMs. Patients with resected CRLMs were randomized after surgery to receive CAPOX and bevacizumab (arm A) or CAPOX alone (arm B) as adjuvant treatment. CAPOX was given in both arms for a total of eight cycles. Bevacizumab was administered for 16 cycles. The primary end point was disease-free survival (DFS). Secondary outcomes were overall survival (OS), toxicity, and quality of life (QoL). In total, 79 patients were randomized. At the time of analysis, 23 events were encountered in arm A and 20 in arm B. One-year DFS rate was 79% [95% confidence interval (CI): 68%-93%] and 68% (95% CI: 55%-85%) for arm A and B, respectively (P=.89). Toxicity was evaluated for 75 patients. No significant differences in toxicity between the two arms were found. QoL scores were higher in arm A, of which emotional functioning and global QoL scores were significant. Adding bevacizumab to a CAPOX regimen in patients undergoing a resection for their CLM is safe and showed higher QoL scores compared with CAPOX alone. Because of premature closure of the study, conclusions about the effect on DFS of additional VEGF inhibition in this setting could not yet be made.

Oxaliplatin-induced laryngospasm - A case report

Oxaliplatin is third-generation platinum compound used in the treatment of colorectal cancer, gastrointestinal cancers, and few other malignancies. It is mostly used in combination regimens with 5-fluorouracil /leucovorin or capecitabine. Neurotoxicity is the major dose-limiting adverse event. Peripheral neuropathy, predominantly of sensory type occurs in 85-95% of patients. Severe immediate hypersensitivity reactions are very rare and generally occurs after the sixth cycle. Here, we report a 54-year-old female with Stage IV colon cancer who developed jaw muscle spasm, suffocation, and dysphonia during the infusion of 3rd cycle of CAPOX regimen. The reaction lasted up to 1 h even after the infusion was stopped and was managed with steroids and antihistamines. Laryngospam is a very rare side effect, so nursing staff and clinicians should be prepared for the management of such hypersensitivity reactions.

Retrospective analysis of the effect of CAPOX and mFOLFOX6 dose intensity on survival in colorectal patients in the adjuvant setting.

Despite lack of a true comparative study, the folfox (5-fluorouracil-leucovorin-oxaliplatin) and capox (capecitabine-oxaliplatin) regimens are believed to be similar in their efficacy and tolerability in the treatment of stage iii colorectal cancer. However, that belief has been disputed, because real-life data suggest that the capox regimen is more toxic, leading to more frequent reductions in the delivered dose intensity-thus raising questions about the effect of dose intensity on clinical outcomes. A retrospective data review for two Canadian institutions, the Segal Cancer Centre and the Tom Baker Cancer Centre, considered patients diagnosed with stage iii colorectal cancer during 2006-2013. Primary endpoints were dose intensity and toxicity, with a secondary endpoint of disease-free survival. The study enrolled 180 eligible patients (80 at the Segal Cancer Centre, 100 at the Tom Baker Cancer Centre). Of those 180 patients, 75 received capox, and 105 received mfolfox6. In the capox group, a significant dose reduction was identified for capecitabine compared with 5-fluorouracil in mfolfox6 group (p = 0.0014). Similarly, a significant dose reduction was observed for oxaliplatin in mfolfox6 compared with oxaliplatin in capox (p = 0.0001). Compared with the patients receiving capox, those receiving mfolfox6 were twice as likely to experience a treatment delay of more than 1 cycle-length (p = 0.03855). Toxicity was more frequent in patients receiving mfolfox6 (nausea: 30% vs. 18%; diarrhea: 47% vs. 24%; peripheral sensory neuropathy: 32% vs. 3%). At a median follow-up of 40 months, preliminary data showed no difference in disease-free survival (p = 0.598). Pooled data from both institutions were also separately analyzed, and no significant differences were found. Our results support the use of capox despite a lack of head-to-head randomized trial data.

FOLFOX or CAPOX perioperative chemotherapy versus postoperative chemotherapy for locally advanced colon cancer: OPTICAL study.

TPS3637Background: In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant chemotherapy with FOLFOX or CAPOX regimens has become a standard treatm...

Oxaliplatin can be safely infused at a rate of 1mg/m2/min.

e14665 Background: Shorter oxaliplatin infusion time would shorten overall treatment time, decompress crowded chemotherapy units, and improve patient satisfaction. Oxaliplatin at a dose of 85mg/m2 is administered over 120 minutes in the standard FOLFOX regimen. An alternative regimen is CapeOx (capecitabine plus oxaliplatin) in which the dose of oxaliplatin is 130mg/m2, also infused over 120 minutes. Not shortening the length of oxaliplatin infusion has been based in large part on concern for hypersensitivity reactions (HSRs) if infused too quickly. Methods: We first reviewed our institutional experience to assure that the rates of HSR were not increased in the Cape Ox regimen, using computerized pharmacy records to identify all patients who received oxaliplatin at our institution between January 1, 2011 and December 31, 2013. Our institutional (pharmacy) adverse drug reporting program was used to identify all HSRs. We then instituted a new policy, as a quality improvement initiative, to infuse all non-re...

Siginificance of platinum concentration in blood and red blood cell in patients with oxaliplatin-based chemotherapy [UMIN000009128

620 Background: Oxaliplatin(Ox) based regimen is widely used in colorectal cancer patients.One of the major adverse effects of Ox is a neuropathy. There is no useful biomarker predicting such adverse effect. The aim of this study is to evaluate platinum concentration as a biomarker predicting the adverse effect. Methods: Ten patients who underwent curative colectomy were included in this study. Final stage of all patients was UICC stage III. All patients underwent adjuvant chemotherapy by CapeOX regimen for eight cycles (or six months). Blood samples were collected after fourth cycle and last cycle. Ox concentration was measured in red blood cells (RBC) and serum, and evaluated the kinetics of platinum (PL) in blood. In addition, we investigated relationship between Ox concentration and adverse effects. Results: 1) Kinetics of PL concentration: PL concentration in RBC tended to be correlated with the difference of RBC numbers between pre- and post-chemotherapy (R2=0.358, p=0.068). The PL concentration in RBC siginificantly correlated with the difference of mean corpuscular volume (MCV) between pre- and post-chemotherapy (R2=0.661, p=0.004). After four cycle, the platinum concentration in RBC siginificantly correlated with the hemoglobin and hematocrit (R2=0.447, p=0.004 and R2=0.425, p=0.041). There was no siginificant difference in PL concentration in both RBC and serum between the points after four cycle and last cycle points (RBC: 1380.5±495.2 ng/ml vs. 1107.0±699.2 ng/ml Aserum: 210.1±38.9 ng/ml vs. 221.2±99.2 ng/ml). 2) PL concentration and adverse effects: PL concentration did not elevate depending on cycle number. There was no siginificant correlations between PL concentrations in RBC or serum and the grade of neuropathy. Conclusions: The PL concentration was significantly related with the difference of RBC numbers and MCV between pre- and post-chemotherapy. However, there was no siginificant relationship between Ox concentration in blood and side effects including neuropathy. So Ox concentration in blood could not be a reliable biomarker for predicting the grade of neuropathy. Clinical trial information: 000009128.

Incidence of Cold-Induced Peripheral Neuropathy and Dose Modification of Adjuvant Oxaliplatin-Based Chemotherapy for Patients with Colorectal Cancer

Background: The CAPOX regimen is used for adjuvant treatment of colorectal cancer. A well-known side effect of oxaliplatin, which often leads to dose modification (DM), is acute neuropathy (AN). AN is provoked by cold, and it could therefore be expected that the degree of AN and thereby DM is more pronounced in the winter period compared to the summer period. Method: Patients with colorectal cancer who received adjuvant CAPOX from January 2005 to August 2011 were reviewed. Out of 108 patients who received adjuvant CAPOX, the oxaliplatin dose was reduced in 92 (85%) patients due to AN. Seventeen out of 31 (55%) patients already had a DM of oxaliplatin in the second cycle during the winter period (December to February; mean temperature 0.1-1.8°C), while in the summer period (June to August; mean temperature 15.1-16.3°C), only 4 (13%) patients needed DM (OR = 2.5, p = 0.022). Conclusion: In this study, we found that the risk of DM and discontinuation of oxaliplatin is highest in the winter period compared to the other seasons. This study draws attention to the importance of training in the proper handling of the acute neurotoxicity of oxaliplatin.

Real-world resource use and costs of adjuvant treatment for stage III colon cancer

Since the generalisability of trial-based economic evaluations may be limited, there is an increasing focus on real-world cost-effectiveness. Real-world studies involve evaluating the effects and costs of treatments in daily clinical practice. This study reports on the real-world resource use and costs of adjuvant treatments of stage III colon cancer in a population-based observational study. Analyses were based on a detailed retrospective medical chart review which was conducted for 206 patients with colon cancer treated in 2005 and 2006 in the Netherlands. Mean total costs per patient were €9681 for 5-FU/LV, €9736 for capecitabine, €32,793 for FOLFOX and €18,361 for CAPOX. Drug costs and the costs related to hospitalisations for chemotherapy administration were the main cost drivers. We identified a potential for substantial cost-savings when the 48 h administration of 5FU/LV in the FOLFOX regimen were to take place in an outpatient setting or be replaced by oral capecitabine as in the CAPOX regimen. This analysis based on detailed real-life data clearly indicates that clinical choices made in oncology based on efficacy of therapy have economic consequences. Considering today's reality of finite healthcare resources, these economic consequences deserve a formal role in clinical decision making, for instance in guideline development.

O1–111 - Phase II Trial of mFOLFOX6/CapeOX Plus Bevacizumab with Oxaliplatin in a Stop and Go Fashion in Advanced mCRC

Background: Combination therapy of bevacizumab (BV) with L-OHP based regimen (such as BV +FOLFOX / BV + CapeOX) is one of the standard therapies against metastatic colorectal cancer (mCRC), however cumulative sensory neurotoxicity of L-OHP results in impairment of patient's quality of life (QoL) and discontinuation of the treatment. although CONcePT trial has shown that intermittent l-OHP administration of BV + FOLFOX7 is safe and effective, it is unknown that the intermittent l-OHP administration is also safe and effective for Japanese patients. Method: We conducted a phase II trial to evaluate the efficacy and safety of intermittent L-OHP administration in first-line BV + mFOLFOX6 or CapeOX therapies in Japanese patients with mCRC. Six cycles of bi-weekly BV + mFOLFOX6 regimen is followed by 6 cycles of bi-weekly BV + sLV5FU2 or 4 cycles of tri-weekly BV + CapeOX regimen is followed by 4 cycles of tri-weekly BV + capecitabine regimen. The choice of mFOLFOX6 or CapeOX was up to the doctor-in charge. Primary endpoint is to evaluate median progression free survival (PFS). Secondary endpoint is to estimate response rate (RR), overall survival (OS), time to treatment failure (TTF), and frequency of neurotoxity (UMIN000002042). Results: Sixty eight patients were enrolled (49 pts are allocated to BV + mFOLFOX6 and 19 pts are allocated to BV + CapeOX ). The median PFS was 347 days (95% CI 286 - 462 days) and TTF was 229days (95% CI 187 - 263days). RR is 51.8% and disease control rate is 98.3%. As the reason of treatment discontinuation, adverse events and progression disease were almost the same number. However grade 3 of peripheral sensory neurotoxicity evaluated by DEB-NTC was not observed. Conclusion: The intermittent L-OHP administration in first-line BV + mFOLFOX6 or CapeOX therapies were also safe and effective for Japanese patients.

Lethal cardiotoxicity, steatohepatitis, chronic pancreatitis, and acute enteritis induced by capecitabine and oxaliplatin in a 36-year-old woman

A 36-year-old female was hospitalized with symptoms suggesting intestinal occlusion. She was diagnosed with adenocarcinoma of the ampulla of Vater (pT4N0 stage) and underwent cephalic duodenopancreatectomy 8 months ago. Five cycles of postoperative chemotherapy were administrated using capecitabine and oxaliplatin (CAPOX or XELOX), the last one being completed 1 month ago. During the present hospitalization, because of normal computed tomography and ultrasound abdominal examination, rehydration and antibiotherapy were administrated. However, 4 days after hospital admission, the patient died. At autopsy and histological examination, we found a severe myocardial sclerosis with large scarring areas, severe steatohepatitis, chronic pancreatitis with large fibrotic areas, and acute enteritis. Alcohol consumption was denied. The patient died due to associated heart, liver and pancreatic failure. This multiorgan toxicity and death following CAPOX regimen had not yet been reported in the literature.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6472150549833105