Infusion Chemotherapy In Patients Research Articles

Adjuvant hepatic arterial infusion chemotherapy in patients with resected hepatocellular carcinoma with microvascular invasion.

Adjuvant hepatic arterial infusion chemotherapy in patients with resected hepatocellular carcinoma with microvascular invasion.

Feasibility of 125I brachytherapy combined with arterial infusion chemotherapy in patients with advanced pancreatic cancer.

To evaluation the feasibility of Iodine-125 (¹²5I) brachytherapy combined with arterial infusion chemotherapy in patients with advanced pancreatic cancer. A total of 72 cases with Stage III and IV were retrospectively reviewed. 23 cases receiving 125I brachytherapy were classified as Group A. 27 cases receiving arterial infusion chemotherapy (gemcitabine + cisplatin, GP) were classified as Group B and 22 cases receiving 125I brachytherapy combined with arterial infusion chemotherapy (GP) were classified as Group C. The evaluated indications were local control rate, survival rate, carbohydrate antigen 19-9, pain relief, and Karnofsky physical scores. Analysis of Variancep, Pearson chi-square test and Kaplan-Meier curves were used for analysis. The local control rate of group A and group C was significantly higher than group B (P < .001). Pearson chi-square test showed statistical difference of the 3 groups (χ2 = 12.969, P = .044). The median survival of group A,B and C was 9 months, 6 months and 13 months, respectively. The survival time of group C was significantly higher than group B (χ2 = 5.403, P = .020). The Log rank test showed statistical difference in the survival curve of the 3 groups (χ2 = 6.501, P = .039). The difference of carbohydrate antigen 19-9 decline percentage between group B and C group was statistically significant (χ2 = 5.959, P = .015). Patients in group A and group C relieved form pain after treatment with statistically significant (P < .001). Pain relief was much more effective in patients who received 125I brachytherapy. Karnofsky physical scores after treatment were statistically higher than those before treatment in each group (P < .001). 125I brachytherapy maybe one of the effective, safe and feasible alternative treatment of advanced pancreatic cancer. ¹²5I brachytherapy combined with arterial infusion chemotherapy was effective in the treatment of advanced pancreatic cancer.

Hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma

Objective:This study’s purpose was to evaluate the response, safety and overall survival of trans-arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with preserved hepatic function.Methods:This study was carried out on 25 patients, diagnosed with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT) and underwent hepatic artery infusion chemotherapy (HAIC). Radiological investigations as Triphasic CT or dynamic MRI liver assessment pre and post therapy were acquired. Intra-Arterial chemotherapeutic agent infusion using only doxorubicin was performed.Results:Neither of the patients who underwent HAIC developed complete or partial response. Only one patient (4.8%) from 21 patients under HAIC had stable disease. 20 patients (95%) had progressive disease. Progressive disease was in form of progression at the primary tumor site in form of increased focal lesion size, number or vascular invasion. Vascular invasion was seen in one patient (4.8%) in the form of hepatic vein thrombosis. Mean progression free survival was about 2.24 ± 0.88 months. Mean overall survival was about 5.72 ± 0.89 months.Conclusion:Our study demonstrated lower clinical efficacy and lower disease control rate of repeated HAIC using doxorubicin only infusion in case of advanced HCC with PVT as compared to combined doxorubicin and cisplatin in previous studies as well as the standard therapy with sorafenib.

Automatic prediction of hepatic arterial infusion chemotherapy response in advanced hepatocellular carcinoma with deep learning radiomic nomogram.

Hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen (oxaliplatin plus fluorouracil and leucovorin) is a promising option for advanced hepatocellular carcinoma (Ad-HCC). As identifying patients with Ad-HCC who would obtain objective response (OR) to HAIC preoperatively remains a challenge, we aimed to develop an automatic and non-invasive model for predicting HAIC response. A total of 458 patients with Ad-HCC who underwent HAIC were retrospectively included from three hospitals (310 for training, 77 for internal validation, and 71 for external validation). The deep learning and radiomic features were extracted from the automatically segmented liver region on contrast-enhanced computed tomography images. Then, a deep learning radiomic nomogram (DLRN) was constructed by integrating deep learning scores, radiomic scores, and significant clinical variables with multivariate logistic regression. Model performance was assessed by AUC and Kaplan-Meier estimator. After automatic segmentation, only a few modifications were needed (less than 30min for 458 patients). The DLRN achieved an AUC of 0.988 in the training cohort, 0.915 in the internal validation cohort, and 0.896 in the external validation cohort, respectively, outperforming other models in HAIC response prediction. Moreover, survival risk stratification was also successfully performed by the DLRN. The overall survival (OS) of the predictive OR group was significantly longer than that of the predictive non-OR group (median OS: 26.0 vs. 12.3months, p < 0.001). The DLRN provided a satisfactory performance for predicting HAIC response, which is essential to identify Ad-HCC patients for HAIC and may potentially benefit personalized pre-treatment decision-making. This study presents an accurate and automatic method for predicting response to hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma, and therefore help in defining the best candidates for this treatment. • Deep learning radiomic nomogram (DLRN) based on automatic segmentation of CECT can accurately predict hepatic arterial infusion chemotherapy (HAIC) response of advanced HCC patients. • The proposed prediction model can perform survival risk stratification and is an easy-to-use tool for personalized pre-treatment decision-making for advanced HCC patients.

Lenvatinib, toripalimab plus hepatic arterial infusion chemotherapy in patients with high-risk advanced hepatocellular carcinoma: A biomolecular exploratory, phase II trial

IntroductionThe combination of lenvatinib, toripalimab and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) suggested encouraging antitumour activity in our retrospective study. We hereby prospectively establish the efficacy, safety and predictive biomarkers of the combination therapy as a first-line treatment in patients with high-risk advanced hepatocellular carcinoma (HCC). Materials and methodsThis phase II, single-centre, single-arm trial enrolled advanced HCC participants with high-risk. Of 51 screened participants, 36 received lenvatinib, toripalimab plus FOLFOX-HAIC. Participants received 21-day treatment cycles of lenvatinib, toripalimab, and FOLFOX-HAIC. The primary end-point was the progression-free survival (PFS) rate per RECIST at six months. ResultsThirty-six participants (86.1% with high-risk features) were enrolled in our study. The primary end-point was met with a PFS rate of 80.6% (95% CI, 64.0%–91.8%) at six months. The median PFS was 10.4 months (95% CI, 5.8–15.0), and the median OS was not reached at the prespecified final analysis and was 17.9 months (95% CI, 14.5–21.3) after follow-up was extended. The ORR per RECIST was 63.9%, and per mRECIST was 66.7%. The median duration of response was 14.4 months (95% CI, 8.9–19.9). The most common adverse events were thrombocytopenia, elevated aspartate aminotransferase, and hypertension, and no treatment-related death was reported. Participants with low levels of both CCL28 and BTC had unsatisfactory prognosis. ConclusionsLenvatinib, toripalimab and FOLFOX-HAIC showed safe and encouraging antitumour activity for advanced HCC with high-risk features. The levels of CCL28 and BTC might be the predictive biomarkers for the triple combination therapy.

Efficacy and Safety of Arterial Infusion Chemotherapy in Patients with Advanced Hepatocellular Carcinoma and Child-Pugh Class B: A Retrospective Cohort Study

Introduction: Although many treatment options are available for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class A, those for patients with CP class B remain limited. We aimed to assess the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil and cisplatin in patients with advanced HCC and CP class B. Methods: Sixty patients who received HAIC with 5-fluorouracil and cisplatin at Kurume Chuo Hospital between April 2012 and March 2021 were recruited. Cisplatin (30 mg administered over 2 h) and 5-fluorouracil (1,250 mg, 72-h constant infusion) were administered to the tumor-feeding artery every 2 weeks. The primary endpoint was overall survival (OS), while the secondary endpoints were progression-free survival and adverse effects. Results: Among the 60 patients, CP class A and class B were noted in 30 patients each. OS did not significantly differ between the two classes. After 4 weeks of HAIC with 5-fluorouracil and cisplatin, 12 patients in the class B group exhibited improved CP scores (CPSs) relative to those at the start of treatment. There was a significant difference in OS between patients whose CPSs had improved and those whose scores remained unchanged or had worsened. Conclusions: HAIC using 5-fluorouracil and cisplatin is effective and safe for patients with CP class B, and improvements in CPSs after 4 weeks of this therapy may represent a predictive marker of treatment efficacy regardless of pretreatment CPS in patients with CP class B.

Triple combination therapy comprising angiogenesis inhibitors, anti-PD-1 antibodies, and hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma.

e16124 Background: The effects of single-drug therapy for the systemic treatment of advanced unresectable hepatocellular carcinoma (HCC) remain unsatisfactory, promoting the emergence of multi-drug and combination therapies. Here we assess the safety and efficacy of a triple combination therapy for treating advanced HCC. Methods: This single-center retrospective study included patients with unresectable HCC treated with triple combination therapy comprising angiogenesis inhibitors (oral apatinib 250 mg/day, lenvatinib 8 mg/day, or sorafenib 400 mg BID), anti-programmed cell death 1 antibodies (iv camrelizumab or sintilimab, 200 mg every 3 weeks), and hepatic arterial infusion chemotherapy (FOLFOX every 4–8 weeks). Eligible patients had completed at least one cycle of therapy and had an imaging assessment. Treatment-related adverse events (TRAEs) were assessed according to the Common Terminology Criteria for Adverse Events. Efficacy data were summarized according to modified RECIST (mRECIST) and RECIST v1.1. Results: Of 34 patients who received triple combination therapy, 25 (19 men and 6 women; median age: 59 years [range: 49–78]) had an imaging assessment. TRAEs were manageable; 28.0% of patients experienced grade 3–4 TRAEs. Efficacy outcomes are summarized in the Table. The objective response rate was 96.0% (mRECIST), the median time to response was 50.5 days (95% CI: 31.02–64.00) and the surgical conversion rate was 56%, indicating a robust therapeutic effect. Overall, 12 patients (48.0%) achieved a complete response (CR), 12 (48.0%) achieved a partial response, and one (4.0%) had stable disease (mRECIST). Fourteen patients (56.0%) underwent surgical resection, after which seven (28.0%) achieved a pathologic CR. After a median follow-up of 9.67 months, no cases of post-operative recurrence or metastasis emerged. Conclusions: Triple combination therapy had a robust therapeutic effect with a high surgical conversion rate in patients with advanced HCC. TRAEs were acceptable, and long-term efficacy is reasonably expected. Summary of efficacy outcomes (n = 25).[Table: see text]

Efficacy of infusion chemotherapy in patients with pulmonary tuberculosis with treatment failure and malabsorption syndrome

Objective. To investigate the effectiveness of infusion chemotherapy in patients with pulmonary tuberculosis (TB) with treatment failure and malabsorption syndrome.&#x0D; Materials and methods. We observed 52 patients with newly diagnosed pulmonary TB with treatment failure, who were diagnosed with malabsorption syndrome. Patients were divided into two groups: 1st group (main) included 24 patients who received rifampicin and ethambutol intravenously, pyrazinamide and isoniazid orally; 2nd group (control) – 28 patients who received standard therapy orally. The severity of malabsorption syndrome was determined by a violation of intestinal penetration. Intestinal penetration was determined by the concentration of lactulose and mannitol (lactulose-mannitol test) in urine. The concentration of rifampicin, isoniazid, ethambutol in the serum was determined by liquid chromatography on a chromatograph Perkin Elmer (USA).&#x0D; Results and discussion. The examination revealed a violation of the rate of intestinal penetration in all studied patients, compared with healthy donors. The concentration of anti-TB drugs in the serum was significantly lower than the therapeutic average in group 2 compared with group 1 (p&lt;0,05). In patients of group 1 after the intensive phase of treatment, the disappearance of clinical symptoms of the disease was observed in 22 (91.3±5.8 %) and 17 (60.7±6.3 %) patients (p&lt;0.05), cessation of mycobacterial excretion – in 20 (83.3±4.3 %) and 14 (50.4±4.6 %) (p&lt;0.05), resorption of infiltrative changes and healing of destruction cavities in the lungs – in 12 (50.2±5.3 %) and 10 (35.7±4.7 %) (p&lt;0.05) compared with group 2.&#x0D; Conclusions. In patients with malabsorption syndrome with ineffective treatment and low intestinal penetration, which leads to reduced serum concentrations of anti-TB drugs in the intensive phase of treatment, it is advisable to increase the effectiveness of intravenous rifampicin and ethambutol.

Treatment intensification with hepatic arterial infusion chemotherapy in patients with liver-only colorectal metastases still unresectable after systemic induction chemotherapy \u2013 a randomized phase II study -- SULTAN UCGI 30/PRODIGE 53 (NCT03164655)- study protocol

BackgroundApproximately 40% of colorectal cancer patients will develop colorectal liver metastases (CRLM). The most effective approach to increase long-term survival is CRLM complete resection. Unfortunately, only 10–15% of CRLM are initially considered resectable. The objective response rates (ORR) after current first-line systemic chemotherapy (sys-CT) regimens range from 40 to 80% and complete resection rates (CRR) range from 25 to 50% in patients with initially unresectable CRLM. When CRLM patients are not amenable to complete resection after induction of sys-CT, ORRs obtained with second-line sys-CT are much lower (between 10 and 30%) and consequently CRRs are also low (< 10%). Hepatic arterial infusion (HAI) oxaliplatin may represent a salvage therapy in patients with CRLM unresectable after one or more sys-CT regimens with ORRs and CRRs up to 60 and 30%, respectively. This study is designed to evaluate the efficacy of an intensification strategy based on HAI oxaliplatin combined with sys-CT as a salvage treatment in patients with CRLM unresectable after at least 2 months of first-line induction sys-CT.Objectives and endpoints of the phase II studyOur main objective is to investigate the efficacy, in term of CRR (R0-R1), of treatment intensification in patients with liver-only CRLM not amenable to curative-intent resection (and/or ablation) after at least 2 months of induction sys-CT. Patients will receive either HAI oxaliplatin plus systemic FOLFIRI plus targeted therapy (i.e. anti-EGFR antibody or bevacizumab) or conventional sys-CT plus targeted therapy (i.e. anti-EGFR or antiangiogenic antibody). Secondary objectives are to compare: progression-free survival, overall survival, objective response rate, depth of response, feasibility of delivering HAI oxaliplatin including HAI catheter-related complications, and toxicity (NCI-CTCAE v4.0).MethodsThis study is a multicenter, randomized, comparative phase II trial (power, 80%; two-sided alpha-risk, 5%). Patients will be randomly assigned in a 1:1 ratio to receive HAI oxaliplatin combined with systemic FOLFIRI plus targeted therapy (experimental arm) or the best sys-CT plus targeted therapy on the basis of their first-line prior sys-CT history and current guidelines (control arm). One hundred forty patients are required to account for non-evaluable patients.Trial registrationClinicalTrials.gov, (NCT03164655). Trial registration date: 11th May 2017.

Acute kidney injury after platinum-based transcatheter arterial chemoembolization and transarterial infusion chemotherapy in patients with hepatocellular carcinoma.

The incidence of acute kidney injury and the association between acute kidney injury and prognosis have been reported about transcatheter arterial chemoembolization using anthracycline. However, the incidence of acute kidney injury after platinum-based transarterial chemoembolization or transarterial infusion chemotherapy remains unclear. The aim of this study was to investigate association between acute kidney injury after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy and prognosis in patients with hepatocellular carcinoma. We retrospectively analysed 270 sessions in 129 patients who underwent platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy. Acute kidney injury was diagnosed according to the criteria established by the International Club of Ascites. The incidence of acute kidney injury, risk factors for serum creatinine elevation and association between acute kidney injury and prognosis were assessed. Fifteen cases of acute kidney injury (5.6%, 15/270) developed in 14 patients (10.8%, 14/129). Ascites (coefficient: 0.059, P=0.006), low estimated glomerular filtration rate (coefficient: -0.008, P=0.029), diabetes (coefficient: 0.072, P<0.001) and high albumin-bilirubin grade (albumin-bilirubin grade 2: coefficient: 0.053, P=0.004; and albumin-bilirubin grade 3: coefficient: 0.103, P<0.001) were significantly associated with an elevation in serum creatinine levels after transcatheter arterial chemoembolization/transarterial infusion chemotherapy. The development of acute kidney injury was associated with poor prognosis (hazard ratio: 3.18, 95%CI: 1.411-7.171, P=0.005). Patients with acute kidney injury had a significantly lower survival rate than patients without acute kidney injury (log-rank test; P=0.034). The incidence of acute kidney injury after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy was consistent with that after transcatheter arterial chemoembolization using anthracycline, and the development of acute kidney injury was associated with poor prognosis. Ascites, diabetes, low estimated glomerular filtration rate and high albumin-bilirubin grade were risk factors for serum creatinine elevation after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy.

Overuse of antianaerobic drug is associated with poor postchemotherapy prognosis of patients with hepatocellular carcinoma.

Overuse of antibiotic drugs alters the composition of gut microbiota and has detrimental effects on the host. In our study, we investigated association of gut flora and antibiotics in the prognosis of patients with liver cancer who have undergone chemotherapy by analyzing two independent clinical studies. We retrospectively subanalyzed a previously reported randomized controlled trial (RCT) on hepatic arterial infusion chemotherapy in patients with hepatocellular carcinoma (HCC) to investigate the association between use of antibiotics and prognosis. In the other study, we prospectively determined the abundance of specific bacterial genus in patients with HCC by sequencing 16S ribosomal RNA and assessed its association with survival. Subanalysis of the RCT data showed that, of 26 types of antibiotics used, administration of carbapenem before or during chemotherapy was associated with poor progression‐free survival (PFS) and overall survival (OS) of patients with HCC (carbapenem + vs. −; median PFS, 78 days vs. 154 days, p = 0.0053; median OS, 177 days vs. 475 days, p = 0.0003). Multivariate analysis revealed that antianaerobic drug use is an independent predictor of poor prognosis. In the prospective study, the abundance of Blautia in fecal microbiota correlated positively with both PFS and OS of patients with HCC who underwent chemotherapy. Use of antibiotics targeting anaerobes is associated with a poor prognosis in patients with HCC who have undergone chemotherapy, whereas the intestinal anaerobic bacteria, Blautia is associated with a good prognosis. These findings might indicate the need for caution regarding overuse of broad‐spectrum antibiotics targeting anaerobes in patients with HCC.

Sorafenib versus hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma: A Japanese multi-center large cohort study.

323 Background: Sorafenib, approved in Japan in 2009, is the first systemic therapy demonstrated to significantly improve overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC). In Japan, hepatic arterial infusion chemotherapy (HAIC), which directly delivers high concentrations of cytotoxic agents to liver tumors, has been offered to patients with advanced HCC since before sorafenib was approved. HAIC is particularly used in patients without extrahepatic metastases (EHM). This study aimed to compare the outcomes of patients with advanced HCC who received HAIC and sorafenib. Methods: Consecutive patients with advanced HCC who received sorafenib or HAIC as the first-line systemic therapy were enrolled from 10 Japanese centers. The statistical analysis plan included pre-defined propensity score matching method and risk factors. All statistical analyses were performed by an independent biostatistician. Results: Between June 2009 and May 2016, 2006 patients were enrolled (sorafenib: 1465 patients, HAIC: 541 patients). The mean OS of patients with macrovascular invasion (MVI) and without EHM was significant longer in the HAIC group compared with the sorafenib group. After propensity score matching, there were 172 patients in each cohort. The OS was 9.1 months for the sorafenib group and 10.1 months for the HAIC group (hazard ratio [HR]: 0.668 [95% CI: 0.475–0.935], P = 0.018). There was no significant difference in OS between patients without both MVI and EHM. After propensity score matching, there were 76 patients in each cohort. The OS was 15.4 months for the sorafenib group and 12.2 months for the HAIC group (hazard ratio [HR]: 1.227 [95% CI: 0.699–2.155], P = 0.475). Conclusions: HAIC might be a potential initial treatment for patients with advanced HCC with MVI (without EHM). Currently, several new drugs appear clinically beneficial for patients with advanced HCC. Although this study only focused on sorafenib as the chemo-agent, additional studies should be conducted to confirm the benefits associated with HAIC in a limited population of patients with advanced HCC.

Proton Beam Therapy in Combination with Intra-Arterial Infusion Chemotherapy for T4 Squamous Cell Carcinoma of the Maxillary Gingiva.

This study aimed to evaluate the therapeutic effect and toxicity of proton beam therapy in combination with intra-arterial infusion chemotherapy in patients with squamous cell carcinoma of the maxillary gingiva. Between December 2010 and March 2016, 30 patients with T4 squamous cell carcinoma of the maxillary gingiva were treated with radiotherapy and retrograde intra-arterial infusion chemotherapy using cisplatin (20–40 mg/m2, 4–6 times). Radiotherapy was basically administered using boost proton beam therapy for primary tumor and neck lymph node tumors, following 36–40 Gy photon radiation therapy delivered to the prophylactic area, to a total dose of 70.4–74.8 Gy. The median follow-up was 33 months. The 3-year local control and overall survival rates were 69% and 59%, respectively. Major grade 3 or higher acute toxicities included mucositis, neutropenia, and dermatitis in 12 (40%), 5 (17%), and 3 (10%) patients, respectively. No grade 3 or higher late toxicities were observed. These results suggested that proton beam therapy in combination with intra-arterial infusion chemotherapy was not inferior to other treatment protocols and should be considered as a safe and effective option in patients with T4 squamous cell carcinoma of the maxillary gingiva.

Randomized, prospective, comparative study on the effects and safety of sorafenib vs. hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with portal vein tumor thrombosis.

Treatment responses of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remain unacceptably low and treatment modalities are limited. We compared the efficacy and safety of sorafenib and hepatic arterial infusion chemotherapy (HAIC). In this randomized, prospective, comparative study, data on 58 patients with advanced HCC with PVTT, with Child-Turcotte-Pugh (CTP) scores of 5-7, were collected from six university hospitals between January 2013 and October 2015. Twenty-nine patients were treated with sorafenib and twenty-nine with HAIC. The median overall survival (OS) and time to progression (TTP) were significantly longer in the HAIC group than in the sorafenib group (14.9 vs.7.2 months, p = 0.012 and 4.4 vs. 2.7 months, p = 0.010). The objective response (OR) rates were 27.6 and 3.4% in the HAIC and sorafenib groups, respectively (p = 0.001). In univariate analysis, sex, main portal vein invasion and treatment modality were significant prognostic factors of OS (p = 0.044, 0.040, 0.015), whereas cause of HCC, tumor number, tumor location and treatment modality were significant prognostic factors of TTP (p = 0.040, 0.002, 0.034, 0.014). In multivariate analysis, sex and treatment modality were significant prognostic factors of OS (p = 0.008, 0.005), whereas cause of HCC, tumor number, tumor location and treatment modality were significant prognostic factors of TTP (p = 0.038, 0.038, 0.015, 0.011). Major complications included hyperbilirubinemia (44.8%), AST elevation (34.5%), ascites (13.8%) and catheter-related complications (3.4%) in the HAIC group and hyperbilirubinemia (34.5%), hand-foot syndrome (31.0%) and AST elevation (27.6%) in the sorafenib group. For managing advanced HCC with PVTT, HAIC may be a valuable treatment modality.

Efficacy of sequential sorafenib plus hepatic arterial infusion chemotherapy in patients with Barcelona Clinic Liver Cancer stage B and C hepatocellular carcinoma: a retrospective single-institution study.

Aim of the studyTo evaluate the efficacy of sequential combination therapy using sorafenib and hepatic arterial infusion chemotherapy (HAIC) in patients with Barcelona Clinic Liver Cancer stage B/C hepatocellular carcinoma (HCC).Material and methodsWe recruited 98 BCLC stage B/C HCC patients at our institute, who received either sorafenib monotherapy or planned sequential sorafenib-HAIC combination therapy. A total of 26 patients (combination group) received sorafenib for one or two months, followed by HAIC with a single dose of cisplatin-lipiodol suspension and a continuous infusion of 5-fluorouracil. Sorafenib-HAIC cycles were repeated every 2–3 months. The remaining 72 patients (control group) were treated with sorafenib alone. Clinical characteristics and treatment outcomes were compared between the groups. Inverse probability weighting (IPW) using propensity scores was applied to adjust for the between-group differences in baseline characteristics.ResultsThe combination group had a significantly lower frequency of extrahepatic metastasis and BCLC stage C disease compared with the control group but had more intrahepatic lesions. The crude median overall survival (OS) was 17.1 months in the combination group compared with 9.7 months in the control group (p = 0.01). The objective response rate was 23.1% in the combination group vs. 6.9% in the control group (p = 0.06). Multivariate analysis identified receipt of sorafenib-HAIC combination (HR: 0.521, 95% CI: 0.297–0.915, p = 0.02) and α-fetoprotein (≥ 400 ng/ml) at baseline as independent factors associated with OS. After adjustment with IPW the combination group still had significantly better OS than the control group (p = 0.04).ConclusionsThe sequential sorafenib-HAIC combination can be an effective and promising treatment option for selected patients with BCLC stage B/C HCC.

Evaluation of early response to hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma using the combination of response evaluation criteria in solid tumors and tumor markers.

To assess the early response and outcome of hepatic arterial infusion chemotherapy (HAIC) in patients with advanced hepatocellular carcinoma (HCC). One hundred sixty-five HCC patients treated with HAIC were reviewed retrospectively. The early response to one course of HAIC treatment was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) and changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP). The median survival time (MST) for all patients was 9.5 months. The early imaging response by RECIST was assessed as partial response (PR), stable disease (SD), and progressive disease (PD) in 32 (19.3%), 86 (52.1%), and 47 (28.4%) patients, respectively. Survival correlated with early imaging response (MST in PR, 20.6; SD, 11.4; PD, 5.0 months; P < 0.0001). The MST was also significantly different in patients with AFP ratio of ≤ 1 or > 1 and DCP ratio of ≤ 1 or > 1 (worst MST, 6.5 months in patients with AFP ratio of > 1 and DCP ratio of > 1). Among patients with SD early imaging response, patients with AFP ratio of > 1 and DCP ratio of > 1 had significantly poorer survival than others (MST 7.4 vs. 12.6 months, P = 0.014). The decrease in AFP and DCP in the early stage treatment with HAIC were identified as significant and independent factors associated with survival of not only all patients, but also patients with SD early imaging response. The use of the combination of RECIST and tumor marker ratio could be useful for assessment of the early response to HAIC and prognosis of patients with advanced HCC.

Continuous intra‐arterial chemotherapy for downstaging locally advanced oral commissure carcinoma

The purpose of this study was to assess the usefulness, safety, and efficacy of intra-arterial (IA) infusion chemotherapy for patients with locally advanced oral commissure cancer. Twenty-one patients with stages III and IV squamous cell carcinoma involving the mouth angle were recruited. Methotrexate (MTX; 50 mg/day) was continuously infused into the external carotid artery for a mean period of 8 days, followed by weekly IA bolus of 25 mg MTX for a mean period of 10 weeks. Thirteen patients (62%) achieved a complete response (CR) and 7 patients (33%) had a partial response (PR). At a median follow-up of 69 months, the estimated 1-year, 3-year, and 5-year survival rates of the patients with CR versus PR were 100% versus 57%, 92% versus 43%, and 80% versus 43%, respectively. Our data demonstrate that continuous IA chemotherapy could achieve a competitive acceptable survival rate and improved locoregional control of advanced oral commissure cancer.

Clinical significance of and future perspectives for hepatic arterial infusion chemotherapy in patients with liver metastases from colorectal cancer

The most common site of metastases in patients with colorectal cancer is the liver. Hepatic resection is considered to be the treatment of choice for liver metastasis from colorectal cancer; however, hepatic resection can be performed in only 20 or 25% of all patients. Recurrence develops in the remnant liver or other organs after hepatic resection in over half of all patients with liver-only metastasis. Hepatic arterial infusion (HAI) chemotherapy can provide relatively high concentrations of drugs to microscopic or macroscopic metastases in the liver, with less toxicity than systemic administration. Meta-analyses have shown HAI chemotherapy to have a significantly higher response rate than systemic chemotherapy and its effect on extrahepatic metastases is negligible. HAI chemotherapy provides much better local control of liver metastases from colorectal cancer than systemic chemotherapy. However, well-controlled studies are needed to elucidate the optimal treatment strategies for neoadjuvant and postoperative adjuvant chemotherapy that optimally combine HAI chemotherapy, molecular targeted agents, and systemic chemotherapy such as FOLFOX or FOLFIRI.

Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial

The perioperative use of a single course adjuvant portal vein infusion chemotherapy in patients with potentially curable colorectal cancer has been shown to significantly improve overall survival but did not reduce the occurrence of liver metastases (SAKK 40/81) [Swiss Group for Clinical Cancer Research (SAKK) Lancet 345(8946):349-353, 1995]. The objective of the present prospective, three-arm randomized multicenter trial was to assess whether peripheral venous administration of adjuvant chemotherapy regimen based on 5-fluorouracil (5-FU) and mitomycin C decreases the occurrence of liver metastases as well as prolongs disease-free and overall survival. Stages I-III colorectal cancer patients (n = 753) were randomized to receive either surgery alone (control arm), surgery plus postoperative portal venous infusion of 5-FU 500 mg/m(2) plus heparin given for 24 hours for seven consecutive days plus mitomycin C 10 mg/m(2) given on the first day (arm 2), or surgery and the same chemotherapy regimen administered by peripheral venous route (arm 3). The 5-year disease-free survival for the three treatment groups were 65% (control group), 60% (portal vein infusion, hazard ratio 1.18, p = 0.23), and 64% (intravenous infusion, hazard ratio 1.04, p = 0.76); the 5-year overall survival was 72% (control group), 69% (portal vein infusion, hazard ratio 1.21, p = 0.2), and 74% (intravenous infusion, hazard ratio 1.03, p = 0.86), respectively. A significant accumulation of early deaths were observed in the portal vein infusion group (p = 0.015). The present prospective randomized multicenter trial provides compelling evidence that short-term perioperative chemotherapy does not improve disease-free and overall survival in patients with potentially curative colorectal cancer. In contrary, the chemotherapy regimen administered in the present investigation seems to have potentially harmful effects, a finding which should be carefully considered in the planning of future trials. Postoperative short-term administration of 5-FU plus mitomycin C either through portal infusion or a central venous catheter is not recommended for routine use in patients with potentially curable colorectal cancer.

Results of Preoperative Hepatic Arterial Infusion Chemotherapy in Patients Undergoing Liver Resection for Colorectal Liver Metastases

Although hepatic artery infusion chemotherapy (HAIC) of floxuridine (FUDR) for colorectal liver metastases (CLM) can produce high response rates, data concerning preoperative HAIC are scarce. The aim of this study was to assess the feasibility and results of liver resection after preoperative HAIC with FUDR. Between 1995 and 2004, 239 patients with isolated CLM received HAIC in our institution. Fifty of these patients underwent subsequent curative liver resection (HAIC group). Short- and long-term results of the HAIC group were compared with the outcomes of 50 patients who underwent liver resection for CLM without preoperative chemotherapy. Postoperative morbidity rate were comparable between the two groups. Overall disease-free survival at 1 and 3 years after hepatectomy were 77.5% and 57.5% in the HAIC group and 62.9% and 37% in the control group (P = .036). Overall survival from diagnosis of CLM at 1, 3, and 5 years were 97%, 59%, and 49% in the HAIC group versus 94%, 48%, and 35% in the control group (P = .097). When patients were stratified according to clinical-risk scoring (CRS) system, patients with more advanced disease at the time of liver resection (CRS > or = 3) had a median survival of 41 months in the HAIC group (n = 37) and 35 months in the control group (n = 34) (P = .031). HAIC of FUDR does not negatively affect the outcome of subsequent liver resection. Preoperative HAIC of FUDR may reduce liver recurrence rate and improve long-term survival in patients with more advanced liver disease.