Hepatic Arterial Infusion Of Oxaliplatin Research Articles

Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin in Hepatocellular Cancer with Extrahepatic Spread

PurposeTo compare treatment with hepatic arterial infusion of chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC) with both extrahepatic spread (EHS) and intrahepatic tumor and patients with intrahepatic tumor only. Materials and MethodsThis single-center retrospective study comprised 116 patients with advanced HCC with both intrahepatic tumor and EHS (EHS group; n = 50) or with intrahepatic tumor only (non-EHS group; n = 66) treated with HAIC including oxaliplatin, fluorouracil, and leucovorin between June 2014 and July 2016. Overall survival (OS) and radiologic responses to treatment were determined and compared between the 2 groups. ResultsBoth the objective response rate and the clinical benefit rate were higher in the non-EHS group than in the EHS group (37.9% vs 16% objective response rate, P = .010; 81.8% vs 62% clinical benefit rate, P = .017). Median OS was not statistically different between the 2 groups (14.8 months vs 9.8 months, P = .068). Subgroup analysis of OS found that patients with lung metastases survived for a shorter time (OS 7 months) than patients with other metastatic sites (P = .003) and patients free of metastases (P = .001). ConclusionsHAIC is a potential treatment option for advanced HCC with limited extrahepatic metastases in a population with hepatitis B virus infection.

556P - Cell free DNA and hepatic arterial infusion of oxaliplatin plus systemic capecitabine for patients with colorectal cancer liver metastases

556P - Cell free DNA and hepatic arterial infusion of oxaliplatin plus systemic capecitabine for patients with colorectal cancer liver metastases

Postoperative hepatic arterial chemotherapy in high-risk patients as adjuvant treatment after resection of colorectal liver metastases - a randomized phase II/III trial \u2013 PACHA-01 (NCT02494973)

BackgroundAfter curative-intent surgery for colorectal liver metastases (CRLM), liver recurrence occurs in more than 60% of patients, despite the administration of perioperative or adjuvant chemotherapy. This risk is even higher after resection of more than three CRLM. As CRLM are mostly supplied by arterial blood flow, hepatic arterial infusion (HAI) of chemotherapeutic agents after resection of CRLM is an attractive approach. Oxaliplatin-based HAI chemotherapy, in association with systemic fluoropyrimidines, has been shown to be safe and highly active in patients with CRLM. In a retrospective series of 98 patients at high risk of hepatic recurrence (≥4 resected CRLM), adjuvant HAI oxaliplatin combined with systemic chemotherapy was feasible and significantly improved disease-free survival compared to adjuvant, ‘modern’ systemic chemotherapy alone.Methods/DesignThis study is designed as a multicentre, randomized, phase II/III trial. The first step is a non-comparative randomized phase II trial (power, 95%; one-sided alpha risk, 10%). Patients will be randomly assigned in a 1:1 ratio to adjuvant systemic FOLFOX (control arm) or adjuvant HAI oxaliplatin plus systemic LV5FU2 (experimental arm). A total 114 patients will need to be included. The main objective of this trial is to evaluate the potential survival benefit of adjuvant HAI with oxaliplatin after resection of at least 4 CRLM (primary endpoint: 18-month hepatic recurrence-free survival rate). We also aim to assess the feasibility of delivering at least 4 cycles of HAI (or i.v.) oxaliplatin after surgical treatment of at least 4 CRLM, the toxicity (NCI-CTC v4.0) of adjuvant HAI plus systemic chemotherapy, including HAI catheter-related complications, compared to systemic chemotherapy alone, and the efficacy of adjuvant HAI on hepatic and extra-hepatic recurrence-free (survival and overall survival).DiscussionIf 18-month hepatic recurrence-free survival is greater than 50% in the experimental arm, the study will be pursued in phase III, for which the primary endpoint will be 3-year recurrence-free survival rate. Patients randomized in the phase II will be included in the phase III, with an additional number of 106 patients.Trial registrationClinicalTrials.gov, NCT02494973. Trial registration date: July 10, 2015.

A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral capecitabine, with or without systemic bevacizumab, for patients with advanced cancer and liver involvement.

2527Background: Hepatic arterial infusion (HAI) of chemotherapy is a treatment option for patients (pts) with cancer metastatic to the liver. We investigated HAI oxaliplatin combined with capecitab...

5-FU or mitomycin C hepatic arterial infusion after failure of arterial oxaliplatin in patients with colorectal cancer unresectable liver metastases

Hepatic arterial infusion (HAI) chemotherapy with oxaliplatin is an accepted option in the management of colorectal cancer (CRC) with dominant liver metastases (LM). However, despite prolonged control, some patients experience disease progression. On the other hand, oxaliplatin leads to dose-limiting toxicity. In these cases, the use of a second-line HAI with an alternative drug has never been reported to date. We evaluated treatment outcomes in patients receiving second-line HAI with 5-FU or mitomycin C, after first-line HAI of oxaliplatin in heavily pretreated patients. Between March 2010 and June 2016, this observational study included 24 patients with unresectable CRC LM and treated with HAI of 5-FU (17 patients) or mitomycin C (7 patients), after HAI of oxaliplatin. Mean age was 61.7years. Forty-two percent of patients (10/24) had extra-hepatic metastases and 75% (18/24) at least 8 liver metastases. Including HAI of oxaliplatin, all patients had previously received at least 2lines of chemotherapy±targeted agents (100%) and 96% (23/24) received concomitant systemic therapies together with HAI of 5-FU or mitomycin C. The overall objective response rate and disease control rate were, respectively, 42% (10/24) and 71% (17/24). Median progression-free survival and overall survival (OS) were, respectively, 5.6 and 25.8months; hepatic progression-free survival was 8.5months. Thirteen percent (3/24) of the patients received further curative intent treatment after HAI 5-FU and mitomycin C. No toxic death occurred and the toxicity profile was acceptable. HAI of 5-FU or mitomycin C is an alternative option in patients with predominant CRC LM, when they experience disease progression or do not tolerate HAI of oxaliplatin.

Efficacy and tolerability of second-line intra-arterial 5FU or mitomycine C after intra-arterial oxaliplatin failure in patients with colorectal cancer and unresectable liver metastases.

e15061 Background: Hepatic arterial infusion (HAI) chemotherapy of oxaliplatin is an option in the management of metastatic colorectal cancers (mCRC) with dominant liver metastases (LM). However, despite prolonged control some patients (pts) experience disease progression or dose-limiting toxicity. In these cases, the use of a second-line HAI with an alternative drug has never been reported to date. This pilot study is evaluating treatment outcomes in pts receiving HAI of 5-FU or mitomycine C (MMC), after HAI oxaliplatin (HAI-ox) in heavily pretreated pts. Methods: 24 pts with unresectable mCRC were enrolled, metastases were exclusively or dominant in the liver (≥80% of overall total metastatic tumour burden in the liver), all pts received prior HAI-ox. They were treated with either biweekly HAI 5-FU with dose ranging from 600 to 1200mg/m2 over 2 hours (17 patients), or monthly MMC 7mg/m2 over 1 hour (7 patients). Results: Mean age was 62 years. 42% of pts (10/24) had extra-hepatic metastases and 75% (18/24) had 8 LM or more. Including prior HAI-ox, pts had previously received a median of 3 prior lines of treatment (range:2 to 5). Previous HAI-ox was stopped for toxicity in 17 pts (allergy, neuropathy or abdominal pain) or progression in 7 pts. At baseline, 62% of pts had progressive disease. All pts but one received concomitant systemic therapies together with HAI 5FU or MMC. The overall RECIST V1.1 objective response rate and disease control rate were respectively 42% (10/24) and 71% (17/24). Median progression free survival (PFS) and overall survival (OS) were respectively 5.6 and 25.8 months; hepatic PFS was 8.5 months. 3 pts benefited from further curative intent treatments after 2nd line HAI (2 radiofrequency, 1 surgery). No toxic death occurred and toxicity profile was acceptable, with only 2 grade 3 events reported (diarrhea and thrombocytopenia). Conclusions: 2nd line HAI with 5-FU or MMC seems feasible and efficient in heavily pretreated mCRC with liver dominant disease when progressing or not tolerating oxaliplatin HAI. A phase II study is going to be performed to confirm these first results.

Postoperative prophylactic hepatic arterial infusion chemotherapy for stage III colorectal cancer: a retrospective study.

BackgroundRadical resection is the main treatment for colorectal cancer (CRC), but metastasis or recurrence is common in which liver metastasis accounted for 83% of the cases. Therefore, the prognosis of patients with advanced CRC may be improved if liver metastasis is prevented. This study aims to investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases of stage III CRC patients after curative resection.MethodsBetween 2002 and 2008, 287 stage III CRC patients who had undergone radical resection were included in this study. According to postoperative adjuvant chemotherapy modality, these patients were divided into two groups. Patients in the combined therapy group received two cycles of HAIC plus four cycles of systemic chemotherapy, while patients in the monotherapy group received six cycles of systemic chemotherapy alone. The HAIC regimen consisted of hepatic arterial infusion of oxaliplatin (OXA, 85 mg/m2) on day 1 and 5-fluorouracil (5-FU, 2,400 mg/m2) on days 2 and 3 followed by a vein infusion of folinic acid (FA, 200 mg/m2) as a 2-hour infusion on days 2 and 3. The systemic chemotherapy regimen consisted of a 2-hour infusion of OXA (85 mg/m2) on day 1 followed by FA (200 mg/m2) as a 2-hour infusion on days 2 and 3, and by 5-FU (2,400 mg/m2) as a 48-hour infusion. This was repeated every 4 weeks. All cases were followed up for 5 years or until death. The 5-year overall survival, disease-free survival, liver metastases-free survival, and the overall liver metastases rates were retrospectively compared.ResultsSignificant differences were found in the 5-year overall survival (combined therapy, 70.71%; monotherapy, 57.14%; P=0.014), disease-free survival (combined therapy, 69.29%; monotherapy, 55.78%; P=0.021), and liver metastases-free survival rates (combined therapy, 70%; monotherapy, 56.46%; P=0.019).ConclusionProphylactic adjuvant HAIC can prevent metachronous liver metastases and improve the prognosis of patients with stage III CRC after curative resection.

The efficacy and safety of hepatic arterial infusion of oxaliplatin plus intravenous irinotecan, leucovorin and fluorouracil in colorectal cancer with inoperable hepatic metastasis

Hepatic arterial infusion (HAI) was evaluated for different drugs to treat hepatic metastasis from colorectal cancer (CRC). Combination treatment with 5-fluorouracil (5-FU), leucovorin, oxaliplatin and irinotecan (FOLFOXIRI) is effective for CRC. A phase II study was conducted to evaluate concomitant HAI administration of oxaliplatin and intravenous leucovorin, 5-FU and irinotecan (FOLFIRI) for patients with inoperable liver metastasis, which had chemotherapy with oxaliplatin (OX) 85 mg/m2 HAI plus systemic intravenous chemotherapy [leucovorin 200 mg/m2, 5-FU 2400 mg/m2 and irinotecan (IRI) 160 mg/m2 in 48 hours]. We treated 24 patients. Neutropaenia was the most frequent toxicity. The main HAI-related toxicity was pain. Two patients (8%) obtained complete response and 17 patients (70%) partial response, giving an objective response rate of 78%. Median follow-up was 22.8 months, and median overall and disease-free survival times were 29 and 20 months, respectively. Therefore, OX HAI and intravenous FOLFIRI is feasible and effective in patients with metastatic CRC.

Early and Late Complications after Hepatic Arterial “Port-a-Cath” Implantation in the Treatment of Hepatic Metastasis from Colorectal Cancer

Background and Aim: In metastatic colorectal cancer, in the last 10 years, hepatic arterial infusion (HAI) was proposed as an alternative using various chemotherapy agents. The insertion of a port-a-cath in the hepatic artery is needed and there are various methods to do that, from classical to interventional approach. Patients and Methods: Patients were selected with metastatic colorectal cancer with inoperable liver metastasis only and were treated with oxaliplatin HAI, combined with systemic intravenously chemotherapy. The port-a-cath insertion was done using the classical approach in the same surgical time with the subclavicular vein port insertion. Results: Thirty-two patients were treated. During our experience we did not encounter intra-operative complications. Among the immediate post-operative complications mainly consisted of metabolic complications (6.2%) and infection was the most common late complication (9.4%). In one case we removed the port-a-cath, thus the patient was not able to continue the treatment. Conclusion: When talking about the safety of the procedure, we didn’t find it to be more at risk for the patients compared to the literature. Even though the antibiotic prophylaxis is done regularly, the risk of infection remains, especially as a late complication.

Transient severe hyperbilirubinemia after hepatic arterial infusion of oxaliplatin in patients with liver metastases

We have observed severe, but rapidly reversible, hyperbilirubinemia in patients receiving hepatic arterial infusion (HAI) of oxaliplatin. We performed a retrospective analysis to characterize this unusual phenomenon. We reviewed the electronic medical records of 113 consecutive patients receiving HAI oxaliplatin to describe the associated hyperbilirubinemia. Four of 113 patients (3.5 %) presented with transient, severe (grade 3/4) hyperbilirubinemia post-HAI oxaliplatin. Peak levels of total bilirubin within 10-16 h of starting HAI oxaliplatin were 4.6, 12.2, 12.8, and 21.2 mg/dL and declined rapidly (within 24 after stopping treatment). One out of four patients experienced severe abdominal pain, and another patient had an infusion reaction (hypertension and hypoxemia) that reversed after discontinuation of infusion. Total bilirubin was predominantly direct. No significant decline in hemoglobin or increase in alkaline phosphatase occurred. Increase in liver transaminases post-infusion was mild to moderate (grades 1-3) and was seen after HAI oxaliplatin regardless of the emerged hyperbilirubinemia. Severe hyperbilirubinemia is a rare but rapidly reversible adverse effect of HAI oxaliplatin and may be accompanied by an abdominal pain syndrome or infusion reaction. Treating physicians should be aware for the potential of this reaction. The mechanism of this unusual reaction merits further investigation.

Oxaliplatin given by hepatic arterial infusion (HAI) or systemic (SYS) with capecitabine in patients (pts) with unresectable liverlimited metastasis (Ur-LLM) from colorectal cancer (CRC).

e14593 Background: Whether therapy of Ur-LLM from CRC by HAI is superior to SYS is unknown. Methods: First line phase II study of pts. with Ur-LLM from CRC. Included were 88 pts. HAI oxaliplatin (100 mg/m2) was given to 66 pts. every 2nd week (wk) for a median of 11 series (1-12) and capecitabine 3500 mg/m2 day 1-7 every 2nd wk for a median of 12 (2-14) series. Vessel variation made HAI unsuitable for 22 pts. They had systemic oxaliplatin (130 mg/m2) for a median of 8 (1-10) series with capecitabine 2000 mg/m2 day 1-14 every 3rd wk for a median of 8 series (1-45) with bevacizumab 7½ mg/kg day 1 in 14 pts. Primary endpoints were response, secondary median overall and therapy free survival (mOS) and toxicity. KRAS mutation status was determined in all pts. with the DxS kit. Survival was evaluated by the Kaplan Meier method and differences with the log rank test. 95% confidence interval are given in brackets. Results: Pts. treated with HAI and SYS were comparable. HAI yielded higher response rates than SYS (table 1). Pts. with KRAS-WT tumors treated with HAI had a mOS of 61 (43-80) mths, with KRAS-MT tumors 28 (21-35) mths (p< 0.0001). SYS in KRAS-WT and MT types yielded equal mOS 36 (27-45) mths and 27 (12-44) mths. Pts. with KRAS-WT tumors treated with HAI lived longer than when treated with SYS (p=0.05). Pts. with HAI with KRAS-WT tumors lived without any kind of therapy for a median of 27 (16-37) mths with 42% living more than 40 mths. with KRAS-MT tumors 8 (3-13) mths (p<0.0001) with 12% living more than 40 mths. Therapy free mOS with SYS in patients with KRAS-WT and KRAS-MT tumors was19 (0-39) mths.for pts. and 12 (4-20) mths respectively with 17% and 22% living more than 2 years.The findings were independent of cetuximab-based therapy in later lines. The toxicity was comparable. Conclusions: Effect of HAI oxaliplatin combined with capecitabine on response and survival is restricted to pts. with KRAS-WT tumors. [Table: see text]

Adjuvant Chemotherapy After Resection of Colorectal Liver Metastases in Patients at High Risk of Hepatic Recurrence

After curatively intended surgery for colorectal liver metastases, liver recurrences occur in more than 60% of patients, despite the administration of adjuvant systemic chemotherapy. The aim of this study was to assess the benefit of combined adjuvant hepatic arterial infusion (HAI) and intravenous (IV) 5-FU compared with standard modern adjuvant IV chemotherapy in patients at high risk of hepatic recurrence. From January 2000 to December 2009, 98 patients, who had undergone curative resection of at least 4 colorectal liver metastases, were selected from a prospective database. Among them, 44 (45%) had received postoperative HAI combined with systemic 5-FU (HAI group) and 54 (55%) had received "modern" systemic chemotherapy (IV group). The 2 groups were similar in terms of age, sex, the stage of the primary, and the administration of preoperative chemotherapy. The median number of HAI cycles received per patient was 7 [range, 1-12]. Twenty-nine patients (66%) had received at least 6 cycles of HAI oxaliplatin, and 22 patients (50%) had received the full planned treatment. For the remaining 22 patients (50%), HAI chemotherapy had been discontinued because of toxicity (n = 8), HAI catheter dysfunction (n = 6), an early recurrence (n = 6), and patient's refusal (n = 2). After a median follow-up of 60 months (51-81 months), 3-year overall survival was slightly higher in the HAI group (75% vs 62%, P = 0.17). Three-year disease-free survival was significantly longer in patients in the HAI group than those in the IV group (33% vs 5%, P < 0.0001). In the multivariate analysis, adjuvant HAI chemotherapy and an R0 resection margin status were the only independent predictive factors for prolonged disease-free survival. Postoperative HAI oxaliplatin combined with systemic chemotherapy after curatively intended surgery of colorectal liver metastases is feasible and may significantly improve disease-free survival of patients at high risk of hepatic recurrence compared with adjuvant modern systemic chemotherapy alone. These results should be confirmed in a randomized study.

Changing Paradigms for Liver Resection of Colorectal Metastases

Prometheus gave mankind wisdom and then suffered the consequences; his liver was eaten each night by eagles and regenerated each day. Surgeons educated by this tale have been resecting liver tumors for years and seeing improve- ment in patients' survival. The criteria for liver resection in patients with metastatic colorectal cancer have undergone a metamorphosis over the last 50 years with even broader boundaries. In Viganoet al.'s 1 article in this issue of the Annals of Surgical Oncology, another potential barrier to liver resection may have been lifted. They report that even for patients whose tumor progresses on chemotherapy, there is benefit from hepatic resection. Previous reports of resection in patients with tumor progression have had poor results. 2,3 Some of the studies may have been too small or had inadequate long-term follow-up. One such report ini- tially described poor results, but on further follow-up and with inclusion of more patients, the authors concluded that there was no difference in survival after liver resection between those whose tumor responded or progressed after neoadjuvant chemotherapy. This may reflect a cautionary tale about retrospective studies that are too small or do not report long-term follow-up. The strength of this report is that it is a large multi-institutional study. 1 Of the 2,143 patients undergoing hepatic resection, 176 patients expe- rienced tumor progression while on systemic neoadjuvant chemotherapy and still had a 35 % 5-year survival. How- ever, since the median follow-up is only 27 months, and most patients in the study were entered after 2006 with data collection stopping in 2010, the 5-year survival is only a projected number. If these results hold up after longer follow-up, Viganoet al.'s study would provide strong support for the use of regional therapy, in this case, hepatic resection, in patients with hepatic-only colorectal metas- tases. An MSKCC study, looking at the question of responders versus nonresponders to chemotherapy prior to liver resection reported no difference in survival in the two groups (59 vs 61 months for the responders vs progression, respectively), with a follow-up time of 63 months. 4 The MSKCC study was a single-institution study where 80 % of patients received postoperative (postop) therapy and 40 % postop hepatic arterial infusion (HAI). The patients whose tumor progressed in the MSKCC study were more likely to have positive margins when undergoing liver resection, a factor not reviewed in the Viganostudy. Vi- gano `'s report also stated that poor-risk patients (more than three metastases, lesions greater than 5 cm, or those with CEA higher than 200 ng/ml) should be treated with further chemotherapy prior to consideration of hepatic resection. Is further systemic chemotherapy useful? Second-line systemic chemotherapy has a low response rate averaging 20 % (range 11-35 %). 5 The median survival from starting second line treatment is about 11 months (range 9-14 months). 5 In Viganoet al.'s analysis, patients who progressed on chemotherapy with one negative factor such as more than three liver metastases have a 29.9 % 5-year survival when they undergo hepatic resection. The chances of being alive at even 3 years with further systemic therapy if a patient has tumor progression on first-line systemic chemotherapy and has poor risk factors is less than 1 %. Use of regional therapy with HAI after progression on systemic therapy may be a more useful approach. Using HAI oxaliplatin and systemic fluorouracil/leucovorin (FU/ LV), Ducreux et al. 6 observed a 64 % response rate in a group of patients where 81 % had not responded to prior systemic chemotherapy. At MSKCC, patients with unre- sectable disease who had received previous systemic chemotherapy and then received HAI-FUDR/dexametha- sone and systemic (SYS) oxaliplatin/irinotecan had a tumor response rate of 85 % with a median survival of 35 months from the time of initiation of HAI. 7 The major toxicities of

Intrahepatic and systemic therapy with oxaliplatin combined with capecitabine in patients with hepatic metastases from breast cancer

BackgroundThe aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease. Patients and methodsSixteen consecutive patients received capecitabine 1300mg/m2 daily combined with oxaliplatin 85mg/m2 every two weeks. Seven patients alternated between intrahepatic and systemic oxaliplatin, and in 9 oxaliplatin was primarily given intrahepatic. Five patients had liver-only metastases and 11 had additionally bone metastases. The patients had received median two previous chemotherapeutic regimens for metastatic disease. ResultsThe response rate was 50% and the stable disease (≥6 months) rate 44%. Median progression free and overall survival was 7.9 and 19.2 months, respectively. The toxicity was moderate with abdominal pain, neuropathy, and hand foot syndrome as the most common adverse events. ConclusionThe combination of capecitabine and intrahepatic/systemic therapy with oxaliplatin was active in pretreated patients with liver metastasis from breast cancer.

Hepatic arterial infusion in colorectal carcinoma: is anatomical targeting still relevant in an era of molecularly targeted therapy?

Historically, metastatic colorectal carcinoma was regarded as a tumor that is relatively resistant to cytotoxic-agents. Due to the limited number of treatment options, methods have been investigated to enhance selectivity. One method for enhancing selectivity is anatomical targeting, including hepatic arterial infusion (HAI). A comprehensive review of the literature. Early studies with HAI used fluoropyrimidines, 5-fluorouracil or floxuridine. Several randomized trials comparing the HAI of fluoropyrimidines with systemic administration of fluoropyrimidines or best supportive care that were conducted in the 1980s and early 1990s demonstrated a superior objective response rate, but usually not a prolongation of survival in patients treated with HAI. The current standard of first line systemic chemotherapy of metastatic colorectal carcinoma is combination chemotherapy (fluoropyrimidines, oxaliplatin and/or irinotecan) administered with targeted agents. A number of trials have reported promising activity of the HAI of oxaliplatin and/or irinotecan with fluoropyrimidines, but only pilot studies are available for the combination of HAI of cytotoxic agents with targeted drugs. Factors that limit the effectiveness and utilization of HAI include catheter or port system related complications, the presence of extrahepatic metastases, or increased risk of hepatic toxicity. HAI could be considered in clinical practice in different settings, including patients after liver resection, as second line therapy in patients failing standard front line regimens and as neodjuvant therapy to convert to resectability. Future studies should specifically concentrate on identifying regimens that would result in increased cure rates in patients with isolated hepatic metastases. For this reason, exploiting anatomical selectivity may still be a useful approach, even in the era of targeted therapy.

Evaluation of the Clinical Relevance of Body Composition Parameters in Patients With Cancer Metastatic to the Liver Treated With Hepatic Arterial Infusion Chemotherapy

The association between body composition parameters and toxicity from hepatic arterial infusion (HAI) chemotherapy regimens has not been analyzed. We assessed data from patients with advanced cancer and liver metastases treated on a clinical trial of a regimen of HAI oxaliplatin combined with systemic 5-fluorouracil/leucovorin and bevacizumab. Correlations between patient characteristics, response, and toxicity and body composition data taken from CT images were analyzed. Forty-eight of 57 patients (mean age 56 yr; 60% women) had available CT scans. The most common diagnosis was colorectal cancer (22/48, 46%); 30/48 patients (63%) had body mass index (BMI) ≥25 kg/m2. Twenty (42%) of 48 patients were sarcopenic. Grade 3–4 adverse events did not differ among patients with and without sarcopenia or according to BMI. The median survival (95% C]) was 167 (128–206) days for sarcopenic and 280 (214–346) days for nonsarcopenic patients (P = 0.271). Among patients treated at the maximum tolerated dose, the median survival was 103 days for sarcopenic and 312 days for nonsarcopenic patients (P = 0.173). Sarcopenia was present in 30% (6/20) of patients with reduction in tumor size posttreatment, and in 52% (14/27) of patients with increased tumor size (P = 0.171). In conclusion, body composition was not significantly associated with toxicities or survival in our small sample.

Durable Remission of Inoperable Liver Metastasis from Rectal Cancer after Hepatic Arterial Infusion of Oxaliplatin and 5-Fluorouracil in Combination with Intravenous Cetuximab

At diagnosis of a cT3N0M1 adenocarcinoma of the rectum with synchronous inoperable liver metastases, a 59-year-old man was treated with preoperative radiotherapy (5×5 Gy), followed by laparoscopy-assisted anterior resection of the rectum with total mesorectal excision. At the first postoperative evaluation, a new lung metastasis was detected. First-line chemotherapy with folfiri (5-fluorouracil, irinotecan, leucovorin) resulted in transient stabilization of the metastatic liver disease. At progression, oxaliplatin and 5-fluorouracil-folinic acid were administered by intrahepatic arterial infusion, in combination with intravenous cetuximab. A partial radiologic response was obtained, with complete metabolic response on fluorodeoxyglucose positron-emission tomography, and normalization of carcinoembryonic antigen values. The solitary lung metastasis was sequentially treated with radiotherapy and resection. Five years after the initial diagnosis, this patient remains free from progression, with residual cystic remnants of the liver metastases visible on conventional computed tomography imaging, but not enhancing with fluorodeoxyglucose positron-emission tomography.

Patients Operated On for Initially Unresectable Colorectal Liver Metastases With Missing Metastases Experience a Favorable Long-Term Outcome

After chemotherapy, complete clinical responses of colorectal liver metastases (CRLMs) increasingly occur, but these responses are rarely complete pathological responses. The management of patients with missing metastases, that is, CRLMs that disappear under chemotherapy are undetectable intraoperatively and finally left in place, continues to be controversial. The aim of this study was to assess the long-term outcome of patients with "missing CRLMs." Between 1999 and 2007, among 523 patients operated on for CRLMs, 96 missing CRLMs were observed and left in place in 27 originally unresectable patients. All of these patients received preoperative chemotherapy. Hepatic arterial infusion (HAI) of oxaliplatin combined with systemic 5-fluorouracil was administered in 23 patients, including 12 before hepatectomy and 11 after. Hepatic surgery was performed after a minimal interval of 3 months during which CRLMs had disappeared on imaging. After a median follow-up of 55 months (24-137) after hepatic surgery, an intrahepatic recurrence was diagnosed in 14 (52%) patients, but the recurrence rate was significantly lower in patients who had received adjuvant HAI compared with the others (27% vs 83%, P = 0.006). Recurrences arose at the site of the missing CRLMs in 9 (33%) patients, but was associated in all cases with another recurrence in the liver. The 5-year overall survival rate of these 27 highly chemosensitive patients was 80%, and the 5-year disease-free survival rate was 23%. Highly chemosensitive patients, whose initially unresectable CRLMs become resectable because of missing CRLMs left in place, have a favorable long-term outcome. Missing CRLMs should not be longer, a contraindication to hepatic surgery. Use of postoperative HAI of oxaliplatin can help to reduce the risk of hepatic relapse.

A phase 1 study of hepatic arterial infusion of oxaliplatin in combination with systemic 5‐fluorouracil, leucovorin, and bevacizumab in patients with advanced solid tumors metastatic to the liver

Liver metastases in patients with cancer are associated with poor survival. The authors of this report conducted a phase 1 study of hepatic arterial infusion (HAI) oxaliplatin combination therapy in patients with advanced cancer and liver metastases. Treatment consisted of escalating doses of HAI oxaliplatin 60 mg/m(2) to 175 mg/m(2) and intra-arterial heparin 3000 IU (Day 1); leucovorin 200 mg/m(2) intravenously (iv) and 5-fluorouracil 300 mg/m(2) bolus plus 600 mg/m(2) iv (Days 1 and 2); and bevacizumab 10 mg/kg iv (Day 3). A conventional "3 + 3" design was used. Fifty-seven patients were treated, including 30 women and 27 men. The median age was 57 years, and the patients had received a median of 3 prior therapies (range, 1-7 prior therapies). The most common cancer was colorectal (n = 29). Overall, 204 cycles were administered (median per patient, 2 cycles; range, 1-17 cycles). The maximum tolerated dose (MTD) of HAI oxaliplatin was 140 mg/m(2). Dose-limiting toxicities were grade 4 thrombocytopenia (n = 1) and grade 4 hypokalemia (n = 1) at 150 mg/m(2) (n = 5). Thirty-three patients (58%) had no toxicity greater than grade 1. The most common toxicities were thrombocytopenia (n = 19), fatigue (n = 15), nausea/vomiting (n = 6), constipation (n = 6), and diarrhea (n = 4). Of 55 patients who were evaluable for response (according to Response Evaluation Criteria in Solid Tumors), 4 patients (7%) had a partial response (PR), and 32 patients (58%) had stable disease (SD), including 15 patients (48%) who had SD for >/=4 months. Of 28 patients with colorectal cancer, 3 patients (11%) had a PR, and 9 patients (32%) had SD for >/=4 months. HAI oxaliplatin combined with systemic 5-fluorouracil, leucovorin, and bevacizumab had antitumor activity in patients with advanced cancer and liver metastases, and the current results indicated that this combination warrants further study. Cancer 2010. (c) 2010 American Cancer Society.

Outcome of colorectal liver metastases vanishing under chemotherapy and finally missing after surgery.

3548 Background: Complete pathological response of colorectal liver metastases (CRLM) after chemotherapy is a rare phenomenon. Furthermore, complete clinical response does not mean complete pathological response, and does not mean cure. However, CRLM may disappear on preoperative imaging studies and become undetectable during hepatectomy, hence left in place and considered as missing CRLM. The aim of this study was to assess the long-term outcome of such missing CRLM. Methods: Between 1999 and 2007, among 523 patients operated for CRLM, missing CRLM were observed in 27 patients (5.1%). All of these patients received preoperative chemotherapy. Hepatic arterial infusion (HAI) of oxaliplatin associated to systemic 5-FU was administrated in 21 patients (10 before hepatectomy and 11 after). Hepatic resection was performed at least 3 months after CRLM vanishing on imaging. Results: These 27 patients initially presented with 286 LM (mean number of LM per patient: 10.6, range: 2-42). Among the 128 vanishing CRLM resected because still detectable during surgery, a complete pathologic response was observed in 29% of cases (n = 37). Overall, 158 missing CRLM were left in place in 27 patients (range per patient: 1 to 37). After a median follow-up of 56 months (15-129), hepatic recurrence was diagnosed in 13 patients (48%), and was significantly lower in patients who received adjuvant HAI compared to others (18% vs. 69%, p = 0.028). Recurrence occurred on the site of missing CRLM in 7 (26%) patients, including only one of the 11 patients who received adjuvant HAI. The overall 5-year survival rate of these highly chemosensitive patients was 85%. Conclusions: Vanishing but not missing metastases are still viable in 71% of cases. Vanishing and missing CRLM are definitively cured in 74% of cases. These excellent results are likely to be due to patient selection (on the duration of response to chemotherapy) and to the administration of adjuvant HAI oxaliplatin. No significant financial relationships to disclose.