Efficacy and quality of life for FOLFOX/bevacizumab +/- irinotecan in first-line metastatic colorectal cancer-final results of the AIO CHARTA trial.

BACKGROUND: FOLFOXIRI plus bevacizumab has demonstrated benefits for metastatic colorectal cancer (mCRC) patients. However, challenges arise in its clinical implementation due to expected side effects and a lack of stratification criteria. METHODS: The AIO "CHARTA" trial randomised mCRC patients into clinical Group 1 (potentially resectable), 2 (unresectable/risk of rapid progression), or 3 (asymptomatic). They received FOLFOX/bevacizumab +/- irinotecan. The primary endpoint was the 9-month progression-free survival rate (PFSR@9). Secondary endpoints included efficacy in stratified groups, QoL, PFS, OS, ORR, secondary resection rate, and toxicity. RESULTS: The addition of irinotecan to FOLFOX/bevacizumab increased PFSR@9 from 56 to 67%, meeting the primary endpoint. The objective response rate was 61% vs. 69% (P = 0.21) and median PFS was 10.3 vs. 12 months (HR 0.83; P = 0.17). The PFS was (11.4 vs. 12.9 months; HR 0.83; P = 0.46) in potentially resectable patients, with a secondary resection rate of 37% vs. 51%. Moreover, Group 3 (asymptomatic) patients had a PFS of 11.1 vs. 16.1 months (HR 0.6; P = 0.14). The addition of irinotecan did not diminish QoL. CONCLUSION: The CHARTA trial, along with other studies, confirms the efficacy and tolerability of FOLFOXIRI/bevacizumab as a first-line treatment for mCRC. Importantly, clinical stratification may lead to its implementation. TRIAL REGISTRATION: The trial was registered as NCT01321957.

Long-term observation of the frequency of secondary colorectal cancer and other malignancies in tyrosine kinase inhibitor treated chronic myeloid leukemia patients and controls.

In this analysis, we examined the risk of secondary malignancies for tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML) patients. We also collected data on specific risk factors for colorectal cancer. Ninety-one patients with CML and 76 controls were included and in total 4 (4.4%) secondary malignancies were found in patients and 8 (10.5%) in controls. The risk for secondary malignancies was not significantly elevated for CML patients (p = 0.141). Two (2.2%) CML patients developed colorectal cancer compared to 4 (5.3%) in the reference group. A higher risk for CML patients for colorectal cancer could not be found (p = 0.414).

Resting heart rate is an independent predictor of death in patients with colorectal, pancreatic, and non-small cell lung cancer: results of a prospective cardiovascular long-term study.

AIMS: Patients with advanced cancer have been shown to suffer from abnormal cardiac function and impaired exercise capacity that may contribute to their impaired quality of life. As tachycardia is considered as a sign of potential early cardiac damage, we sought to determine whether resting heart rate and other ECG-derived variables have prognostic value. METHODS AND RESULTS: From 2005 to 2010, we enrolled 145 patients with histologically confirmed cancer (36 colorectal, 72 pancreatic, and 37 non-small cell lung cancer patients) and 59 healthy controls. During a mean follow-up of 27 months, 82 patients (57%) died from any cause. The mean resting heart rate of healthy subjects was 70 ± 13 b.p.m., and that of cancer patients was 79 ± 14 b.p.m. (P< 0.0001). As a sensitivity analysis, we excluded control subjects taking a beta-blocker, but resting heart rate remained increased in cancer patients vs. controls (P < 0.0001). Resting heart rate ≥75 b.p.m. [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.16-2.94; P = 0.01] significantly predicted survival in univariable analyses and remained an independent predictor of survival in a multivariate model (HR 1.67, 95% CI 1.01-2.78; P = 0.04). Furthermore, the heart rate stayed significant in a second model that included age and sex as well. CONCLUSION: The present study is the first to show that resting heart rate independently of haemoglobin and tumour stage predicts survival in patients with advanced colorectal, pancreatic, and non-small cell lung cancer, and may therefore represent a therapeutic target.

Upfront FOLFOXIRI+bevacizumab followed by fluoropyrimidin and bevacizumab maintenance in patients with molecularly unselected metastatic colorectal cancer.

BACKGROUND: The addition of bevacizumab (BEV) to standard doublet chemotherapy improves outcomes compared with chemotherapy alone in patients with metastatic colorectal cancer (mCRC). The OPAL study examined the effect of BEV+FOLFOXIRI followed by 5FU/LV and BEV maintenance on progression-free survival (PFS) in patients with previously untreated unresectable mCRC. METHODS: Eligible patients had histologically confirmed mCRC, ECOG performance status ⩽1 and were 18-70 years old. Patients received up to 12 cycles of FOLFOXIRI+BEV q2w (induction phase) followed by up to ⩽40 cycles of 5FU/LV+BEV q2w (maintenance phase). Median PFS was the primary end point; secondary end points included response, OS, secondary resection rate, safety and prognostic value of pharmacogenetic profiling. RESULTS: Ninety-seven patients were enrolled. Of these, 90 received study medication and formed the safety population: 64 males; median age 58 (range 28-71) years; ECOG performance status 0/1 in 54%/46% patients; and liver only disease in 35 patients. Relative dose intensities were 79-85% for all four drugs. The incidence of adverse events (AEs) was as previously reported and there were no new safety signals. In total, 87 serious AEs occurred in 39 patients (43%). Median PFS was 11.1 months (95% CI 9.4-12.0) and did thus not meet the primary objective of 12 months. Median OS was 32.2 months (95% CI 22.6-36.9). Fifty-two patients were pharmacogenetically profiled. CONCLUSIONS: FOLFOXIRI+BEV was feasible in this molecularly unselected mCRC patient population, showing a high efficacy in terms of survival, overall response and secondary resection rate. Pharmacogenomic profiling revealed no clinically relevant marker.

Lymph node count and prognosis in colorectal cancer: the influence of examination quality.

Colorectal cancer guidelines recommend adjuvant chemotherapy in stage II disease when less than 12 lymph nodes are assessed. The recommendation bases on previous studies showing an association of a low lymph node count and adverse outcome. Compared to current standards, however, the quality of lymph node examination in the studies was low. We, therefore, investigated the prognostic role of <12 lymph nodes in cancers diagnosed adherent to current quality measures. Stage I-IV colorectal cancers from 1,899 patients enrolled into a population-based cohort study were investigated for the prognostic impact of a lymph node count <12. The stage specific share of patients diagnosed with ≥12 nodes (stage I-IV: 62, 85, 85, 78%, respectively) was used to compare lymph node examination quality to other studies. We found no impact of a lymph node count <12 on overall, cancer-specific or recurrence-free survival for any tumour stage. Compared to studies reporting an adverse prognostic impact of a low lymph node count in stages II and III the stage-specific shares of patients with ≥12 nodes were markedly higher in this study (85% vs. 24-58% in previous analyses) and this correlated with increased rates of stage III compared to stage II cancers. In conclusion our data indicate, that the previously reported effect of a low lymph node count on the patients' outcomes is eliminated by improved lymph node examination quality and thus question the general applicability of a 12 lymph node cut off for adjuvant chemotherapy decision making in stage II disease.

Cardiovascular function and predictors of exercise capacity in patients with colorectal cancer.

BACKGROUND: Patients with colorectal cancer (CRC) often present with dyspnea and fatigue. These are also frequent symptoms in patients with chronic heart failure (CHF). OBJECTIVES: We hypothesized that similar patterns of cardiovascular perturbations are present in CRC and CHF. METHODS: We prospectively studied 50 patients with CRC, 51 patients with CHF, and 51 control subjects. The CRC group was divided into 2 subgroups: patients who underwent chemotherapy (n = 26) and chemotherapy-naive patients (n = 24). We assessed exercise capacity (spiroergometry), cardiac function (echocardiography), heart rate variability (Holter electrocardiography), body composition (dual-energy x-ray absorptiometry), and blood parameters. RESULTS: Compared with the control arm, the left ventricular ejection fraction (CRC group 59.4%; control group 62.5%) and exercise performance as assessed by peak oxygen consumption (peak VO2) (CRC group 21.8 ml/kg/min; control group 28.0 ml/kg/min) were significantly reduced in CRC patients (both p < 0.02). Markers of heart rate variability were markedly impaired in CRC patients compared with control subjects (all p < 0.008). Compared with the control group, the CRC group also showed reduced lean mass in the legs and higher levels of the endothelium-derived C-terminal-pro-endothelin-1 (both p < 0.02). Major determinants of cardiovascular function were impaired in chemotherapy-treated patients and in the chemotherapy-naive patients, particularly with regard to exercise capacity, left ventricular ejection fraction, lean mass, and heart rate variability (all p < 0.05 vs. control subjects). CONCLUSIONS: Some aspects of cardiovascular function are impaired in patients with CRC. More importantly, our findings were evident independently of whether patients were undergoing chemotherapy.

Interventionally implanted port catheter systems for hepatic arterial infusion of chemotherapy in patients with primary liver cancer: a phase II-study (NCT00356161).

BACKGROUND: Hepatic arterial infusion (HAI) of chemotherapy requires the implantation of a transcatheter application system which is traditionally performed by surgery. This procedure, but particularly the adjacent drug application via pump or port is often hampered by specific complications and device failure. Interventionally implanted port catheter systems (IIPCS) facilitate the commencement of HAI without need for laparatomy, and are associated with favorable complication rates. We here present an evaluation of the most important technical endpoints associated with the use of IIPCS for HAI in patients with primary liver cancers. METHODS: 70 patients (pts) with hepatocellular (HCC, n=33) and biliary tract cancer (BTC, n=37) were enrolled into a phase II -study. Of those, n=43 had recurrent disease and n=31 suffered from liver-predominant UICC-stage IVb. All pts were provided with IIPCSs before being treated with biweekly, intraarterial chemotherapy (oxaliplatin, 5-Flourouracil, folinic acid). The primary objective of the trial was defined as evaluation of device-related complications and port duration. RESULTS: Implantation of port catheters was successful in all patients. Mean treatment duration was 5.8 months, and median duration of port patency was not reached. Disease-progression was the most common reason for treatment discontinuation (44 pts., 63%), followed by chemotherapy-related toxicity (12 pts., 17%), and irreversible device failure (5 pts., 7%). A total of 28 port complications occurred in 21 pts (30%). No unexpected complications were observed. CONCLUSIONS: HAI via interventionally implanted port catheters can be safely applied to patients with primary liver tumors far advanced or/and pretreated.

Non-invasive assessment of cardiac hemodynamics in patients with advanced cancer and with chronic heart failure: a pilot feasibility study.

INTRODUCTION: Relationships between cardiac pressure and volume have been suggested as markers of cardiac contractility; parameters include stroke work and the maximal rate of pressure rise during isovolumic contraction (dP/dtmax). Patients with cancer often display dyspnea and fatigue. These are also frequent symptoms in patients with chronic heart failure (HF). The reasons for similar symptoms in cancer patients are unknown. Using the novel Nexfin Finapres technique, we sought to assess measures of cardiac performance in patients with cancer and compare these values with those from control subjects and patients with chronic HF. MATERIAL AND METHODS: We prospectively studied 98 patients (control n = 18, chronic HF n = 37, advanced pancreatic or colorectal cancer n = 43) and assessed blood pressure (BP), stroke volume (SV), cardiac output (CO), and dP/dtmax at rest. RESULTS: All parameters of interest could be assessed using the Nexfin Finapres technique with SV and CO being significantly higher in patients with cancer than in controls (both p < 0.05). The SV was significantly higher in patients with chronic HF than in controls (p < 0.05). In patients with cancer, SV correlated with age (r = -0.45, p < 0.01) and body weight (r = +0.55, p = 0.0001). In chronic HF, SV declined with increasing age (r = -0.49, p < 0.01); in control subjects, SV increased with increasing body weight (r = +0.57, p = 0.01). CONCLUSIONS: Patients with cancer tended to display elevated BP, CO, SV, and dP/dtmax as compared to control subjects and patients with HF. These findings may reveal an elevated risk for cardiovascular diseases in this group.

Treatment with bevacizumab and FOLFOXIRI in patients with advanced colorectal cancer: presentation of two novel trials (CHARTA and PERIMAX) and review of the literature.

BACKGROUND: More than half of patients with colorectal cancer will develop metastatic disease either evident at the time of initial diagnosis or during their course of disease. Besides multidisciplinary management further treatment intensification is warranted to improve the still limited prognosis. METHODS/DESIGN: In these two multi-centre, randomized phase II trials, conducted in Germany, 380 patients with R0-resectable colorectal liver metastases (PERIMAX) and with unresectable, metastatic colorectal cancer (CHARTA) will be recruited. Patients previously untreated for metastatic disease with either synchronous or metachronous metastases are randomly assigned in a 1:1 ratio to resection of colorectal liver metastases followed by postoperative FOLFOX for 6 months or perioperative FOLFOXIRI and bevacizumab for 3 months pre- and postoperative and resection (PERIMAX), or to induction chemotherapy with FOLFOX and bevacizumab +/- irinotecan for a maximum of 6 months followed by maintenance treatment with fluoropyrimidine and bevacizumab. The primary objective of these trials is to evaluate the feasibility and efficacy of FOLFOXIRI and bevacizumab in metastatic colorectal cancer. Primary endpoint is failure free survival rate at 18 months in the PERIMAX trial and progression free survival rate at 9 months in CHARTA. Secondary objectives include efficacy, safety and tolerability. DISCUSSION: The CHARTA and PERIMAX trials are designed to evaluate the benefits and limitations of a highly active four-drug regimen in distinct treatment situations of metastatic CRC. Eligible patients are classified into resectable liver metastases to be randomized to perioperative treatment with FOLFOXIRI and bevacizumab or postoperative FOLFOX in the PERIMAX, or unresectable metastatic CRC to be randomized between FOLFOX and bevacizumab with or without irinotecan, stratified for clinical groups according to disease and patients' characteristics in the CHARTA trial. TRIAL REGISTRATION: Clinical trial identifier CHARTA: NCT01321957, PERIMAX: NCT01540435.

Matched-pair comparison of radioembolization plus best supportive care versus best supportive care alone for chemotherapy refractory liver-dominant colorectal metastases.

PURPOSE: This study was designed to evaluate overall survival after radioembolization or best supportive care (BSC) in patients with chemotherapy-refractory liver-dominant metastatic colorectal cancer (mCRC). METHODS: This was a matched-pair comparison of patients who received radioembolization plus BSC or BSC alone for extensive liver disease. Twenty-nine patients who received radioembolization were retrospectively matched with a contemporary cohort of >500 patients who received BSC from 3 centers in Germany. Using clinical databases, patients were initially matched for prior treatments and tumor burden and then 29 patients were consecutively identified with two or more of four matching criteria: synchronous/metachronous metastases, tumor burden, increased ALP, and/or CEA >200 U/ml. Survival was calculated from date of progression before radioembolization or BSC by using Kaplan-Meier analysis. RESULTS: Of 29 patients in each study arm, 16 pairs (55.2%) matched for all four criteria, and 11 pairs (37.9%) matched three criteria. Patients in both groups had a similar performance status (Karnofsky index, median 80% [range, 60-100%]). Compared with BSC alone, radioembolization prolonged survival (median, 8.3 vs. 3.5 months; P < 0.001) with a hazard ratio of 0.3 (95% confidence interval, 0.16-0.55; P < 0.001) in a multivariate Cox proportional hazard model. Treatment-related adverse events following radioembolization included: grade 1-2 fatigue (n = 20, 69%), grade 1 abdominal pain/nausea (n = 14, 48.3%), and grade 2 gastrointestinal ulceration (n = 3, 10.3%). Three cases of grade 3 radiation-induced liver disease were symptomatically managed. CONCLUSIONS: Radioembolization offers a promising addition to BSC in treatment-refractory patients for whom there are limited options. Survival was prolonged and adverse events were generally mild-to-moderate in nature and manageable.

Changes in hepatic blood flow during whole body hyperthermia.

PURPOSE: Changes in blood flow distribution are important for heat dispersion and for supportive therapeutic strategies such as simultaneous whole body hyperthermia (WBH) and administration of chemotherapy. The aim of this clinical study was to determine changes in hepatic blood flow during WBH for the treatment of metastatic cancer. MATERIALS AND METHODS: This observational clinical study was part of a phase I/II feasibility study of WBH. WBH was induced using a radiant heat device. Hepatic blood flow was estimated using indocyanine green clearance measurements. The plasma disappearance rate of indocyanine green (PDR-ICG) was recorded in percent/min. We used an invasive thermo-dye-dilution technique to estimate hepatic blood flow, cardiac output, and volume status. Mean arterial blood pressure was also measured invasively. To determine the effects of hyperthermia the measurements were performed at defined temperature points. RESULTS: In 10 of 22 treatments the PDR-ICG fell below normal values during hyperthermia, which represented a significant fall in hepatic blood flow. Cardiac output, volume status, and mean arterial blood pressure did not differ between patients whose liver blood flow was reduced and those whose liver blood flow remained unchanged. CONCLUSIONS: We observed distinct reductions in hepatic blood flow during WBH, which suggested a significant redistribution of blood flow away from the core during WBH. This was not mirrored by global circulatory parameters.

Adult jejunojejunal intussusception caused by metastasized pleomorphic carcinoma of the lung: report of a case.

Adult small-intestinal intussusception is rare and very different from childhood intussusception. Both benign and malignant pathologies can underlie small intestinal intussusception in adults, but malignancy is much less frequent. We report a case of jejunojejunal intussusception caused by an intestinal metastasis of the sarcomatoid component of pleomorphic carcinoma of the right lung. The patient, a 61-year-old man, underwent successful segmental jejunal resection. Adult small bowel intussusception, though an unusual cause of acute abdomen, requires early diagnosis and timely management. To our knowledge, this is the first report of adult jejunojejunal double intussusception caused by metastatic sarcomatoid carcinoma of the lung.

Phase II feasibility study on the combination of two different regional treatment approaches in patients with colorectal "liver-only" metastases: hepatic interstitial brachytherapy plus regional chemotherapy.

The aim of this study was to evaluate the feasibility, safety, and efficacy of combined treatment with hepatic interstitial brachytherapy (HIB) and hepatic arterial infusion (HAI) of chemotherapy after interventional implantation of port catheter systems. Thirty-three patients with unresectable "liver-only" metastases of colorectal cancer were treated with both HIB and HAI during the course of their disease. All 33 patients had recurrent disease and 27 had received previous chemotherapy. Of these, 15 received HAI first and were then consolidated with HIB, 9 started with HIB and were continued with HAI, and 9 received first HIB and subsequently HAI after hepatic disease progression. Patients were evaluated for treatment characteristics, side effects, and efficacy. Comparisons between treatment groups were also performed. The median tumor diameter of metastases treated with brachytherapy was 4.6 cm (range: 1-12 cm). The median minimal irradiation dose inside the tumor margin was 18 Gy administered to a mean of two metastases in 69 interventions. Minor (n = 4) and major (n = 3) complications occurred in 10% of interventions. WHO grade III adverse events of the regional chemotherapy were observed in seven patients; grade IV, in one patient. At a median follow-up of 28 months (range: 7-74 months), the median time to disease progression after first treatment was 10.5 months (range: 1-35 months). Of 138 metastases treated by brachytherapy, 16 local recurrences were seen (mean, 12.3 months; range, 3-45 months). No signs of hepatic failure were observed in any of our patients. In conclusion, combinations of two minimally invasive therapeutic methods are feasible, with acceptable complication rates, and provide promising results in colorectal cancer patients with unresectable hepatic metastases.

Planning transarterial radioembolization of colorectal liver metastases with Yttrium 90 microspheres: evaluation of a sequential diagnostic approach using radiologic and nuclear medicine imaging techniques.

The purpose of the study was to establish a diagnostic approach to the preparation of patients with colorectal liver metastases considered for transarterial radioembolization (RE). Twenty-two patients sequentially underwent computed tomography (CT; thorax/abdomen), magnetic resonance imaging (MRI; liver; hepatocyte-specific contrast), positron emission tomography (PET/PET-CT; F18-fluoro-desoxy-glucose), and angiography with perfusion scintigraphy [planar imaging; tomography with integrated CT (SPECT-CT)]. The algorithm was continued when no contraindication or alternative treatment option was found. The impact of each test on the therapy decision and RE management was recorded. Patient evaluation using CT revealed contraindications for RE in 4/22 patients (18%). Of the remaining 18 patients, 2 were excluded and 3 were assigned to locally ablative treatment based on MRI and PET results (28%). The remaining 13 patients entered the planning algorithm: SPECT-CT revealed gastrointestinal tracer accumulations in 4 (31%) patients [SPECT, 2 (15%)], making a modified application necessary. In five patients (38%), planar scintigraphy revealed relevant hepatopulmonary shunting. Therapy was finally administered to all 13 patients without therapy-related pulmonary or gastrointestinal morbidity. Each part of the diagnostic algorithm showed a relevant impact on patient management. The sequential approach appears to be suitable and keeps the number of unnecessary treatments and therapy risks to a minimum.

The effect of induced hyperthermia on the immune system.

Therapeutical hyperthermia has been considered for cancer therapy since William Coley observed tumour remission after induction of fever by bacterial toxins at the end of the 19th century. Because fever is associated with a variety of immunological reactions, it has been suspected, that therapeutical hyperthermia might also activate the immune system in a reproducible manner and thereby positively influence the course of the disease. During the last decade, new insight has been gained regarding the immunological changes taking place during therapeutic hyperthermia. In this chapter, we review the most relevant data known about the effect of hyperthermia on the immune system with special focus on alterations induced by therapeutical whole-body hyperthermia (WBH) in cancer patients.

Cetuximab: appraisal of a novel drug against colorectal cancer.

Cetuximab (C225, Erbitux, Merck, Darmstadt, Germany) is a human-mouse chimeric therapeutic monoclonal antibody (mAb) that competitively binds to the extracellular domain of the human epidermal growth-factor receptor (EGFR). It has been developed out of the murine antibody M225 "from bench to bedside" in less than two decades, and is the anti-EGFR mAb furthest ahead in clinical evaluation. In Europe, cetuximab is approved for the treatment of patients with EGFR-expressing, metastatic colorectal cancer after failure of treatment with irinotecan since 2004, and for the treatment of patients with locally advanced squamous cell cancer of the head and neck concomitant to radiotherapy since 2006. We here summarize the current role of cetuximab in the treatment of colorectal cancer, give an overview on the ongoing studies, address the most important controversies, and point out the chances and challenges for the future use of cetuximab in colorectal cancer and other human malignancies.

Intraoperative fresh-frozen plasma versus human albumin in craniofacial surgery--a pilot study comparing coagulation profiles in infants younger than 12 months.

The transfusion of fresh-frozen plasma (FFP) is suggested to minimize dilution coagulopathy when applied instead of colloids during paediatric craniofacial surgery (pCFS). We prospectively compared plasmatic haemostaseologic function between volume replacement with FFPs versus human albumin (HA) in a pilot study. Thirty infants with primary craniosynostosis were scheduled for pCFS. In 15 of those, FFPs were available from the identical donor as for packed red blood cells (pRBC), and were thus employed for intraoperative volume replacement. The remaining 15 infants were infused with HA-5% instead. Haemoglobin(Hb)-values, global coagulation parameters (activated partial thromboplastin time-aPTT; prothrombin time-PT), selected clotting factors (F) (VIII, XI, XIII), antithrombin-AT, fibrinolytic factors (fibrinogen; plasminogen; alpha2-antiplasmin-alpha2A), and activation parameters (thrombin-antithrombin-complex-TAT; plasmin-antiplasmin-complex-PAP; D-dimers) were assessed and compared between both groups after induction of anaesthesia, before transfusion of pRBC, and at the end of surgery. Patients and treatment characteristics were balanced between both groups. Prolongation of aPTT and decreases of PT, FXI, FXIII, AT3, and fibrinolytic factors were more pronounced in the HA-group. Increases in F VIII activity, activation parameters, and the course of Hb-values were similar among both groups. There was no difference regarding clinical endpoints (peri-/postoperative pRBC-transfusions, postoperative blood loss). In conclusion, the application of HA was associated with a more distinct dilution of procoagulant factors, AT3, and fibrinolytic factors than the use of FFPs. However, the course of activation markers suggested a similar extent of clotting and fibrinolytic activation with the use of both transfusion regimens, and there were no differences with regard to clinical endpoints.

Interventionally implanted port catheter systems for hepatic arterial infusion of chemotherapy in patients with colorectal liver metastases: a Phase II-study and historical comparison with the surgical approach.

BACKGROUND: The high complication rates of surgically implanted port catheter systems (SIPCS) represents a major drawback in the treatment of isolated liver neoplasms by hepatic arterial infusion (HAI) of chemotherapy. Interventionally implanted port catheter systems (IIPCS) have evolved into a promising alternative that enable initiation of HAI without laparatomy, but prospective data on this approach are still sparse. Aim of this study was to evaluate the most important technical endpoints associated with the use of IIPCS for the delivery of 5-fluorouracil-based HAI in patients with colorectal liver metastases in a phase 2-study, and to perform a non-randomised comparison with a historical group of patients in which HAI was administered via SIPCS. METHODS: 41 patients with isolated liver metastases of colorectal cancer were enrolled into a phase II-study and provided with IIPCS between 2001 and 2004 (group A). The primary objective of the trial was defined as evaluation of device-related complications and port duration. Results were compared with those observed in a pre-defined historical collective of 40 patients treated with HAI via SIPCS at our institution between 1996 and 2000 (group B). RESULTS: Baseline characteristics were balanced between both groups, except for higher proportions of previous palliative pre-treatment and elevated serum alkaline phosphatase in patients of group A. Implantation of port catheters was successful in all patients of group A, whereas two primary failures were observed in group B. The frequency of device-related complications was similar between both groups, but the secondary failure rate was significantly higher with the use of surgical approach (17% vs. 50%, p < 0.01). Mean port duration was significantly longer in the interventional group (19 vs. 14 months, p = 0.01), with 77 vs. 50% of devices functioning at 12 months (p < 0.01). No unexpected complications were observed in both groups. CONCLUSION: HAI via interventionally implanted port catheters can be safely provided to a collective of patients with colorectal liver metastases, including a relevant proportion of preatreated individuals. It appears to offer technical advantages over the surgical approach.