Combined Intra-arterial Chemotherapy Research Articles

Results of complex treatment of patients with operable pancreatic head cancer using preoperative intra-arterial chemotherapy in combination with radiation therapy in multifractionation mode

The aim of this study was to assess the safety and efficacy of treating patients with operable pancreatic cancer after preoperative intra-arterial infusion of chemotherapy combined with conformal radiation therapy in a multi-fractionation mode. Patients (n = 40) were randomized into two groups: the main one – intra-arterial infusion of chemotherapy + radiation therapy + surgery (n = 20), and control – intra-arterial infusion of chemotherapy + surgery (n = 20). Neoadjuvant therapy consisted of intra-arterial infusion of chemotherapy (chemoembolization of a pancreatic head tumor with oxaliplatin 85 mg/m2) followed by intra-arterial chemo infusion with gemcitabine 1000 mg/m2. In the main group, radiation therapy was also carried out in two fractions per day, 2 Gy with an interval of 4–6 hours, 5 days a week, up to a total dose of 50 Gy. In the main group, the lower incidence of postoperative pancreatitis and the pancreatic fistulas were statistically confirmed, the incidence of grade 2 therapeutic pathomorphisis increased, as well as the median life expectancy.

Invasion of the pterygoid plates: an indicator for regional lymph node failure in maxillary sinus cancer

BackgroundThe aim of this study was to evaluate the long-term treatment results of combined superselective intraarterial chemotherapy and radiation therapy for advanced maxillary sinus cancer (MSC) and the incidence of regional lymph node failure, and to reveal the clinical and anatomical predictive factors for metastasis.MethodsWe retrospectively evaluated 55 consecutive patients with locally advanced squamous cell carcinoma of the maxillary sinus who were treated with external radiotherapy and superselective intraarterial chemotherapy. Elective nodal irradiation (ENI) was performed only in the clinical node-positive (cN+) cases and not in the clinical node-negative (cN0) cases. Results: Thirty-eight patients were cN0, and 17 were cN+ at diagnosis. Regional lymph node metastases occurred in 7 of 38 patients with cN0, and 2 of 17 with cN+ during the median follow-up period of 36 months. There were more cases of high-grade (3 or 4) late adverse events in the ENI group than in the non-ENI group (13% vs. 41%, respectively; p = 0.03). In cN0 cases without ENI, invasion of the pterygoid plates (57% vs. 90%; p < 0.01) and oral cavity (35% vs. 92%, with invasion vs without invasion, respectively; p = 0.02) was significantly correlated with a low 5-year regional recurrence-free rate.ConclusionsPatients with MCS and invasion of the pterygoid plates and oral cavity can be considered appropriate candidates for ENI.

Combined intra-arterial chemotherapy and intravitreal melphalan for the treatment of advanced unilateral retinoblastoma.

To evaluate the efficacy and safety of combined intra-arterial chemotherapy (IAC) and intravitreal melphalan (IVM) for the treatment of advanced unilateral retinoblastoma. This retrospective study involved 30 consecutive eyes from 30 Chinese patients with advanced unilateral retinoblastoma. All patients were initially treated with IAC combined with IVM. The clinical status and complications were recorded at each visit. The International Intraocular Retinoblastoma Classification groups were D in 23 eyes and E in 7 eyes. All eyes showed severe cloud vitreous seeds at the first visit. The mean number of IAC cycles and intravitreal injections was 3.2 (range, 3-4) and 6 (range, 1-14), respectively. The median follow-up time was 29mo (range, 7-36mo). Treatment success with regression of the retinal tumor and vitreous seeds was achieved in 29 of 30 eyes (96.7%). Globe salvage was attained in 93.3% (28/30) eyes, and enucleation (n=2) was performed due to neovascular glaucoma and persistent vitreous hemorrhage. Complications included retinal pigment epithelium (RPE) atrophy (n=13; 43%), mild lens opacity (n=7; 23%), vitreous hemorrhage (n=5; 17%) and rhegmatogenous retinal detachment (n=1; 3%). No extraocular tumor extension or metastasis occurred. Combined IAC and IVM is effective and safe for the treatment of advanced unilateral retinoblastoma.

Intra-arterial chemotherapy combined with intravesical chemotherapy is effective in preventing recurrence in non-muscle invasive bladder cancer.

To evaluate the efficacy and safety of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IC) in non-muscle invasive bladder cancer (NMIBC) and identify the risk factors for recurrence and progression. This is a retrospective cohort study of NMIBC patients in south China. Ninety-nine patients underwent IAC combined with transurethral resection of bladder tumor (TURBT) and IC, and 50 patients underwent TURBT plus IC without IAC. The 5-year outcomes of the two groups were compared. Cox regression was used to evaluate risk factors. Kaplan-Meier curves were used to assess the significant differences of recurrence-free survival and progression-free survival. At 5 years, IAC significantly reduced the recurrence of high-grade NMIBC, 54.5% (18/33) in the non-IAC group vs 30.5% (18/59) in the IAC group (p = 0.028). IAC significantly reduced the recurrence of high-risk NMIBC, 56.3% (18/32) in the non-IAC group vs 26.1% (18/69) in the IAC group (p = 0.007). IAC significantly reduced the recurrence of intermediate-risk NMIBC, 44.4% (8/18) in the non-IAC group vs 22.2% (6/27) in the IAC group (p = 0.030). Tumors numbering from 2 to 7 had the highest recurrence rate (18.1%, 27/149). In this aspect, there was a significantly lower recurrence rate in the IAC group (30.8%, 12/30) than in the non-IAC group (68.2%, 15/22) (p = 0.007). No significant difference was found in the progression rate between the two groups. Only two cases (2/99, 2.0%) in the IAC group showed progression. The results of univariate and multivariate analyses suggested that the number of tumors, grade and risk level were risk factors for recurrence. No difference was found with respect to gender, age, tumor diameter, and T category. In the Kaplan-Meier plot, recurrence-free survival was significantly associated with treatment strategies (p < 0.01). Recurrence-free survival was shorter in the non-IAC group (12.73 ± 7.56months) than in the IAC group (17.88 ± 12.26months). Combined IAC is a promising procedure to prevent recurrence and may be useful to suppress progression in NMIBC patients. The independent risk factors for the recurrence of NMIBC were multifocal tumors, grade and risk level. Intra-arterial chemotherapy is an effective and safe procedure and may be a promising choice in areas where BCG is not available or for patients who are intolerant to BCG.

SUVmax on FDG-PET is a predictor of prognosis in patients with maxillary sinus cancer.

Our aim was to determine whether the maximum standardized uptake value (SUVmax) of the primary lesion demonstrated by [(18)F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is associated with the prognosis of maxillary sinus cancer. The relationships of clinicopathological factors including age, T stage, N stage, histologic type, treatment strategy, and primary tumor SUVmax with progression-free (PFS) and overall (OS) survival were evaluated using the log-rank test and Cox method in 31 patients with maxillary sinus cancer before combined superselective intra-arterial chemotherapy using high-dose cisplatin with concurrent radiotherapy, or radiotherapy alone. The median duration of follow-up was 55.4(range 9.7-72.6)months. PFS and OS of patients exhibiting a high SUVmax (≥16 and≥17, respectively) for the primary tumor were significantly lower than those of patients for whom the primary tumor SUVmax was low (p=0.0010 and p=0.033, respectively). Multivariate analyses showed that T stage (p=0.0049) and primary tumor SUVmax (p=0.026) were independently prognostic of poorer PFS and that only primary tumor SUVmax (p=0.049) was independently prognostic of poorer OS. SUVmax of the primary tumor determined by FDG-PET/CT before treatment could be a good surrogate marker for prognostication of maxillary sinus cancer.

Surgical technology catheterization hepatic arteri under selective intra-arterial chemotherapy

Developed and introduced into clinical practice methods of hepatic artery catheterization through the right gastro-omental artery and (or) the right gastric artery, which let you quickly and without risk of bleeding catheter set for different types of blood supply to the liver for selective intraarterial chemotherapy. After catheterization of hepatic artery own output stump artery with a catheter through a tunnel formed in the round ligament of the liver in kontraperturny puncture in the right upper quadrant and left in this state for the whole period of treatment, or set subcutaneous arterial port. Method angiostomy allow transport of anticancer drugs directly to the target organ, and on the other hand delimit the prepared arterial vessel from the free abdominal cavity. Selective intra-arterial chemotherapy on the described method was performed in 326 patients with liver metastases from colorectal cancer. During or after treatment, complications occurred in 17 patients, accounting for 5.2%. In determining the extent of reactions NCI toxicity scale was used. The proposed method of treatment allows for selective intraarterial combination chemotherapy in patients with different variants of the blood supply to the liver. It is advisable in all cases produce a block lymphadenectomy gate liver exposing the structures of the celiac trunk and cholecystectomy. The proposed sequence of actions in the performance of selective intra-arterial chemotherapy can simultaneously take into account the anatomical variations, as well as to avoid possible mistakes and complications.

Prognostic value of post-treatment (18)F-FDG PET/CT for advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy.

To clarify the prognostic value of post-treatment (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in patients with advanced head and neck squamous cell carcinoma (HNSCC) after combined intra-arterial chemotherapy and radiotherapy (IACR). Thirty-six patients with HNSCC who underwent IACR were recruited. The period from the end of IACR to the last post-treatment (18)F-FDG PET/CT examination was 8-12 weeks. Both patient-based and lesion-based analyses were used to evaluate the PET/CT images. For lesion-based analysis, 36 regions (12 lesions of recurrences and 24 scars at primary sites) were selected. The Kaplan-Meier method was used to assess the overall survival (OS) stratified by (18)F-FDG uptake or visual interpretation results. Twelve patients with recurrence were identified by six months after IACR. The sensitivity and specificity in the patient-based analysis were 67% (8/12) and 88% (21/24), respectively. The mean OS was estimated to be 12.1 months (95% CI, 6.3-18.0 months) for the higher maximum standardized uptake value (SUVmax) group (n=7) and 44.6 months (95% CI, 39.9-49.3 months) for the lower SUVmax group (n=29). OS in the higher SUVmax group (cut-off point, 6.1) or positive visual interpretation group was significantly shorter than that in the lower SUVmax or negative visual interpretation group (P<0.001 and P<0.05, respectively). The SUVmax and visual interpretation of HNSCC on post-IACR (18)F-FDG PET/CT can provide prognostic survival estimates.

Influence of etiology on host immunity in liver cirrhosis patients with advanced hepatocellular carcinoma receiving intra-arterial chemotherapy.

We have shown that continuous intra-arterial combination chemotherapy (IACC) might be more effective for advanced HCC (aHCC) in patients with HCV-related (C-LC) or alcoholic (A-LC) liver cirrhosis (LC) patients than in patients with HBV-related LC (B-LC). This study retrospectively assesses the difference of etiology on host immunity in LC patients with aHCC treated by IACC. Forty-seven adult LC patients with aHCC were treated by IACC between 2005 and 2008, with inoperable tumors according to CT findings. IACC (LV at 12 mg/hr, CDDP at 10 mg/hr, and 5-FU at 250 mg/22 hr) was delivered via the proper hepatic artery every 5 days for 4 weeks using a catheter connected to a subcutaneously implanted drug delivery system. The control group comprised 13 healthy volunteers. Twelve of the 47 patients with aHCC had B-LC, 27 had C-LC, and 8 had A-LC. In the B-LC group, 1 out of 12 patients had a Japan Integrated Staging (JIS) score of 2, 4 had a JIS score of 3, 7 had a JIS score of 4, and no patients had a JIS score of 5, while the respective numbers were 6, 9, 10 and 2 in the C-LC group, and 1, 1, 5 and 1 in the A-LC group. The response rates were 37.0%, 37.5% and 8.3% in the C-LC, A-LC and B-LC group, respectively. In the C-LC group, the percentage of Th1 cells before and after chemotherapy was significantly higher than in the control group. In the B-LC group, the percentage of Th2 cells after chemotherapy was significantly higher than that in the control group. However, there were no significant differences of Th1 and Th2 cells between the A-LC group and the control group. These results indicate that IACC was more effective for aHCC in A-LC patients with normal Th1/Th2 balance and in C-LC patients without Th2 dominance than in B-LC patients who showed Th2 dominance after chemotherapy.

Comparing Intra-Arterial Chemotherapy Combined With Intravesical Chemotherapy Versus Intravesical Chemotherapy Alone: A Randomised Prospective Pilot Study for T1G3 Bladder Transitional Cell Carcinoma After Bladder-Preserving Surgery

To compare the efficacy of intra-arterial chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder transitional cell carcinoma (BTCC) followed by bladder-preserving surgery. Sixty patients with T1G3 BTCC were randomly divided into two groups. After bladder-preserving surgery, 29 patients (age 30-80 years, 24 male and 5 female) received intra-arterial chemotherapy in combination with intravesical chemotherapy (group A), whereas 31 patients (age 29-83 years, 26 male and 5 female) were treated with intravesical chemotherapy alone (group B). Twenty-nine patients were treated with intra-arterial epirubicin (50 mg/m(2)) + cisplatin (60 mg/m(2)) chemotherapy 2-3 weeks after bladder-preserving surgery once every 4-6 weeks. All of the patients received the same intravesical chemotherapy: An immediate prophylactic was administered in the first 6 h. After that, therapy was administered one time per week for 8 weeks and then one time per month for 8 months. The instillation drug was epirubicin (50 mg/m(2)) and lasted for 30-40 min each time. The end points were tumour recurrence (stage Ta, T1), tumour progression (to T2 or greater), and disease-specific survival. During median follow-up of 22 months, the overall survival rate, tumour-specific death rate, recurrence rate, progression rate, time to first recurrence, and adverse reactions were compared between groups. The recurrence rates were 10.3 % (3 of 29) in group A and 45.2 % (14 of 31) in group B, and the progression rates were 0 % (0 of 29) in group A and 22.6 % (7 of 31) in group B. There was a significant difference between the two groups regarding recurrence (p = 0.004) and progression rates (p = 0.011). Median times to first recurrence in the two groups were 15 and 6.5 months, respectively. The overall survival rates were 96.6 and 87.1 %, and the tumour-specific death rates were 0 % (0 of 29) and 13.5 % (4 of 31) in groups A and B, respectively. During the intra-arterial chemotherapy cycle, although more than 50 % patients experienced some toxicities, most were minor and reversible [grade 1-2 (46.7 %) vs. grade 1-2 (6.9 %)]. These findings suggest that combining intra-arterial chemotherapy with intravesical chemotherapy could delay tumour recurrence and progression compared with intravesical chemotherapy alone and this type treatment is relatively safe.

Intra-arterial Combination Chemotherapy with Maximum Transurethral Resection of Bladder Tumour for T1 Grade 3 and T2--3N0M0 Bladder Cancers

Purpose: We evaluated the clinical outcomes following intra-arterial chemotherapy with maximum transurethral resection of bladder tumour (TURBT) for patients with T1 grade 3 (G3) and T2--3N0M0 bladder cancers. Material and methods: Patients were 27 males and 7 females with a median age of 63.6 years. With the cooperation of an interventional radiologist, cisplatin (100 mg/m2), methotrexate (30 mg/m2) and adriamycin (20 mg/ body) were administered via a catheter in 2 cycles every 4 weeks. Results: The 5-year cancer-specific survival rate in T1 G3, T2 and T3 was 100.0%, 57.3% and 50.0%, respectively. In T2--3N0M0 cases, complete response (CR) and non-CR were seen in 13 (46.4%) and 15 cases (53.6%), respectively. Response to treatment proved to be the most significant prognostic predictor of cancerspecific survival by multivariate analysis in T2--3N0M0 cases. T2--3N0M0 cases with ?2 prognostic predictors at staging TURBT (age >70 years, male, size >3 cm and the presence of hydronephrosis) had an unfavourable outcome. There was a statistical association between the number of prognostic predictors at staging TURBT and response to treatment. Conclusion: These results suggest that our protocol prevents disease progression in T1 G3 cases, but that it is not suitable for T2--3N0M0 cases with ?2 prognostic predictors at staging TURBT.

Multimodal therapy for liver cirrhosis patients with advanced hepatocellular carcinoma

We have previously shown that continuous intra-arterial combination chemotherapy (IACC) might be more effective for advanced hepatocellular carcinoma (aHCC) in patients with HCV-related liver cirrhosis (C-LC) or alcoholic liver cirrhosis (A-LC) than in patients with HBV-related LC (B-LC). However, it is still unknown whether IACC actually improves the prognosis of aHCC patients with liver cirrhosis (LC), because it is difficult to perform a randomized controlled trial for patients with a poor prognosis. The aim of this study was to retrospectively assess the influence of IACC on the prognosis of aHCC. Fifty-eight adult Japanese patients who had aHCC and LC underwent repeated trans-arterial chemoembolization (TACE) without IACC between 1990 and 1997 at our hospital (group T), while 43 patients with aHCC and LC received IACC between 2000 and 2008 after undergoing several TACE sessions (group R). The Japan Integrated Staging score (JIS score) of each patient was≥3 at the time of presentation, except for patients with tumor thrombi involving the first or subsequent portal vein branches or those with tumor invasion of the inferior vena cava. The same IACC regimen was repeated for as long as possible in group R. In group T, 13 patients had B-LC, 37 patients had C-LC, and 8 patients had A-LC, while the respective numbers were 14, 21, and 8 in group R. The median survival time (MST) was 248days for patients with C-LC in group T and 708days for those in group R, while it was 253days for patients with A-LC in group T and 593days for those in group R. There were significant differences of survival between the two groups. However, MST was 369days for patients with B-LC in group T and 782days for those in group R, without a significant difference. In group R, a complete or partial response was achieved after 4weeks of chemotherapy in 14.3% of patients with B-LC versus 42.9% of patients with C-LC and 37.5% of patients with A-LC. In LC patients with a JIS score>3 at diagnosis, multimodal therapy with IACC after TACE prolongs the MST of C-LC or A-LC patients compared with TACE alone, although it does not improve the MST of patients with B-LC.

18F-FDG versus 11C-choline PET/CT for the imaging of advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy: the time period during which PET/CT can reliably detect non-recurrence

The purpose of this prospective study was to evaluate the usefulness of (18)F-fluorodeoxyglucose (FDG) and (11)C-choline positron emission tomography (PET)/computed tomography (CT) for detecting recurrences of advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy. Additionally, we surveyed the time period during which an effective negative predictive value could be maintained after the first follow-up PET/CT examination and estimated the optimal timing of a second PET/CT examination for detecting late recurrences. Fifty-three subjects (36 men and 17 women; mean age: 59.4 +/- 11.5 years) with advanced head and neck squamous cell carcinoma were recruited. Post-treatment (18)F-FDG PET/CT and (11)C-choline examinations were performed in all patients between 8 and 12 weeks after combined intra-arterial chemotherapy and radiotherapy. The PET/CT images were evaluated using a patient-based analysis and a lesion-based analysis. All of the patients were prospectively followed for at least 9 months after the post-treatment PET/CT examination, with surveillance using conventional images (including CT and/or MRI) and a physical examination performed every 3 months. Recurrences, as determined using the patient-based analysis, were eventually confirmed in 18, 6 and 5 patients at 3, 4-6 and 7-9 months after the post-treatment PET/CT examination, respectively. The sensitivity and specificity of the 18F-FDG PET/CT and the 11C-choline PET/CT examinations to predict recurrence within 3 months were higher (FDG: 89 and 91%; choline: 83 and 80%, respectively) than for recurrence detection 6 months (FDG: 67 and 90%; choline: 62 and 76%, respectively) and 9 months later (FDG: 59 and 92%; choline: 55 and 75%, respectively). The lesion-based analysis showed that the maximum standardized uptake value of (18)F-FDG and (11)C-choline in the recurrent lesions were correlated with each other, compared with their relation in scar tissues (R (2) = 0.492 and 0.197, respectively). (11)C-choline was not superior to (18)F-FDG for the detection of recurrent head and neck cancer. Both modalities had difficulty identifying recurrences at 4-9 months after the post-treatment PET/CT examination. In patients with advanced head and neck cancer who have received combined therapy, a second post-treatment PET/CT examination to check for late recurrences should be performed within 4-6 months after the first post-treatment PET/CT examination.

Hepatotoxicity of intra-arterial combination chemotherapy in patients with liver cirrhosis and advanced hepatocellular carcinoma

We have previously reported that 24-h intra-arterial combination chemotherapy (IACC) prolongs the survival of patients with advanced hepatocellular carcinoma (aHCC). However, it has also been reported that 5-fluorouracil (5-FU) exacerbates liver damage in patients with liver cirrhosis (LC). The aim of this study was to clarify the hepatotoxicity of IACC in LC patients with aHCC. Twenty-one adult Japanese patients (20 men and 1 woman) with aHCC and LC underwent IACC between 2004 and 2007 at our hospital. These patients showed multiple partial responses or stable disease, except for five patients who showed no response and three patients with tumors more than 30 mm in diameter. All patients had inoperable disease on the basis of computed tomography (CT) findings. IACC (leucovorin at 12 mg/h, cisplatin at 10 mg/h, and 5-FU at 250 mg/22 h) was delivered via the proper hepatic artery every 5 days for 4 weeks. Twelve patients were in Child-Pugh class A (group A), and nine were in class B (group B). The Child-Pugh score was significantly increased after chemotherapy compared with before chemotherapy in both groups. Serum albumin was significantly decreased after chemotherapy, and the number of patients with ascites also increased after chemotherapy. Serum type IV collagen and N-terminal propeptide of type III procollagen were significantly increased after chemotherapy, although there was no significant change in serum aminotransferases. IACC might cause hepatotoxicity that induces fibrosis without releasing aminotransferases.

Bladder Preservation Therapy Conducted by Intra-arterial Chemotherapy and Radiotherapy for Muscle Invasive Bladder Cancer

A previous paper reported favorable results of intra-arterial chemotherapy in combination with radiotherapy for muscle-invasive bladder cancer. The current study will update those results. Between January 1992 and December 2006, 94 patients with confirmed muscle invasion were treated with intra-arterial chemotherapy and concurrent radiotherapy after an initial complete transurethral resection. Intra-arterial chemotherapy consisted of cisplatin (Days 1-3) and pirarubicin (Days 8-10), and radiation was administered with the chemotherapy (2 Gy/session) with a total dosage of 44 Gy. The median age was 67.0 years. There were 60 patients in T2, 19 patients in T3 and 15 patients in T4. The median follow-up period was 72.9 months in the survivors. Among these patients, 84 patients (89.4%) obtained a complete response (CR) and 10 patients did not achieve a CR. Between the CR and non-CR patients, the clinical stage and the existence of hydronephrosis were significantly different. The cause-specific survival rates at 5 and 10 years were 76.2% and 67.5%, respectively. The overall survival rates at 5 and 10 years were 66.6% and 47.4%, respectively. A Cox proportional hazard model showed that only the cause-specific survival rate was associated with a CR after treatment. The bladder preservation rates were 89.7% at 5 years and 87.6% at 10 years. Myelosuppression was the major adverse event but it was manageable. Non-hematological sever adverse events were rare. Bladder preservation therapy shows good survival and good bladder preservation rates. Clinical stage T2 and the absence of hydronephrosis are favorable factors.

Changes of host immunity in relation to efficacy in liver cirrhosis patients with advanced hepatocellular carcinoma treated by intra-arterial chemotherapy

It is known that tumors develop mechanisms to escape from the immune system and to inhibit antitumor responses. The aim of this study was to retrospectively assess changes of host immunity in relation to efficacy in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) treated by combined intra-arterial chemotherapy. Thirty-seven adult Japanese LC patients with aHCC were treated by intra-arterial combination chemotherapy. The control group was composed of 19 adult Japanese patients with chronic hepatitis C diagnosed by pathological examination of liver biopsy specimens. All control patients were stage 1 according to the fibrosis score of Desment. Ten of the 37 patients (group PR) showed a partial response and 17 of the 37 patients (group SD) showed stable disease, but 10 of the 37 patients (group PD) showed no response. There were no significant differences in the percentage of Th1 cells between any of the groups either before or after chemotherapy. The percentage of Th2 cells was significantly higher in group PD before and after chemotherapy than in the control group (P < 0.05 by Tukey's test). Although there was no significant difference, the percentage of Th2 cells was higher in group SD than in group PR. The percentage of Th2 cells increased in LC patients with aHCC as the efficacy of intra-arterial combination chemotherapy decreased. These results indicated that intra-arterial chemotherapy might be not useful for patients with aHCC, because it induces Th2 dominant host immunity.

Influence of the etiology of liver cirrhosis on the response to combined intra-arterial chemotherapy in patients with advanced hepatocellular carcinoma

We have previously reported that intra-arterial chemotherapy prolongs the survival of patients with advanced HCC (aHCC); however, whether the response to intra-arterial chemotherapy depends on the etiology of underlying liver cirrhosis (LC) is still unknown. The aim of this study was to assess any influences of the etiology of LC on the response to combined intra-arterial chemotherapy for aHCC. A total of 53 adult Japanese LC patients (46 men and 7 women) with aHCC were treated with combined intra-arterial chemotherapy between 2002 and 2007 at our hospital. All of the patients had a Japan Integrated Staging (JIS) score of 3 or 4. Their tumors were inoperable according to computed tomography findings. Combined intra-arterial chemotherapy was administered via the proper hepatic artery every 5 days for 4 weeks and the chemotherapy regimen was continued for as long as possible. There were 15 patients with HBV infection (B-LC group), 29 patients with HCV infection (C-LC group), and nine patients with alcoholic cirrhosis (A-LC group). The percentage of patients with a complete or partial response after 4 weeks of chemotherapy was 0% in the B-LC group versus 31.0% in the C-LC group and 44.4% in the A-LC group. The survival of the A-LC and C-LC groups was significantly longer than that of the B-LC group with the median survival time being 688, 368, and 211 days, respectively. Combined intra-arterial chemotherapy might be more effective for aHCC in patients with A-LC or C-LC than in patients with B-LC.

Therapeutic Strategy of Advanced Hepatocellular Carcinoma by Using Combined Intra-Arterial Chemotherapy

The majority of primary liver cancer is hepatocellular carcinoma (HCC). HCC has increased in many countries, particularly where hepatitis C virus infection is more common than hepatitis B virus infection. Several non-surgical treatment options, including transcatheter arterial embolization, percutaneous ethanol injection, microwave coagulation, and radiofrequency ablation have been developed and are widely used for unresectable HCC. However, these modalities are not indicated for patients with multifocal disease, invasion or thrombosis of major blood vessels, and poor liver function. The majority of patients with advanced hepatocellular carcinoma (aHCC) do not survive for longer than 6 months from the time of diagnosis. Combined intra-arterial chemotherapy is one of the few remaining options for patients with aHCC. Continuous local arterial infusion of 5-fluorouracil (5-FU) and cisplatin (CDDP) via an infuser pump and implanted reservoir has been shown to prolong the survival of patients with aHCC. When LC patients with aHCC undergo chemotherapy, we should consider the influence of both tumor factors and host immunity. This review focuses on therapeutic strategy of patients with aHCC by using combined intra-arterial chemotherapy and the influence of host immunity on the response to such chemotherapy based on our results. The present article shows some recent patents related to the field.

Treatment results of continuous intra-arterial CBDCA infusion chemotherapy in combination with radiation therapy for locally advanced tongue cancer

The objective of this study was to improve the treatment results for locally advanced tongue cancer. A combination of radiotherapy with continuous intra-arterial therapy using CBDCA was used. According to TNM staging (1997), 29 patients had stage III lesions and 11 patients had stage IV (M0) lesions. A catheter was inserted through the lingual artery in 26 patients, through the external carotid artery in 11 patients, and through the faciolingual trunk in 2 patients. CBDCA was continuously infused for 4 to 6 weeks. With IA chemotherapy, external irradiation (median dose: 46.8 Gy) was simultaneously performed, and 1 to 2 courses of systemic chemotherapy were performed in 19 patients before intra-arterial chemotherapy. The 5-year local control rate was 65%. The 5-year OS rate was 39.5%. There were no clinically significant adverse side effects. Continuous IA CBDCA and concurrent radiation therapy can be delivered safely with good efficacy for locally advanced carcinoma of the tongue.

Th1/Th2 balance: an important indicator of efficacy for intra-arterial chemotherapy

It has been reported that Th2 cytokines down-regulate antitumor immunity, while activation of type 1 T cells promotes antitumor immunity. However, the immunological features of liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) treated by intra-arterial chemotherapy are still unclear. The aim of this study was to assess the influence of intra-arterial combination chemotherapy on the Th1/Th2 balance in LC patients with aHCC. Twenty-one adult Japanese LC patients with aHCC were treated by intra-arterial combination chemotherapy. The control group was composed of 20 adult Japanese patients with chronic hepatitis C diagnosed from examination of liver biopsy specimens. All control patients were over 55 years old and were stage 1 according to the fibrosis score of Desment. Thirteen of the 21 aHCC patients (group R) showed an objective response, but the other 8 patients (group N) showed no response. There were no significant differences of Th1 cells between group R and group N either before or after chemotherapy. Although there was no significant difference from group R, group N had a significantly higher percentage of Th2 cells than the control group both before and after chemotherapy (p < 0.05 by Tukey's test). These results indicate that the Th1/Th2 balance might be a useful indicator of the effect of intra-arterial combination chemotherapy in LC patients with aHCC. Inhibition of an increase of Th2 cells might be important for the efficacy of intra-arterial chemotherapy in such patients.

Changes of cytokines in cirrhosis patients with advanced hepatocellular carcinoma treated by intra-arterial chemotherapy

Tumor necrosis factor (TNF) induces cancer cell-specific apoptosis by binding to a TNF-related apoptosis-inducing ligand. Binding of the Fas ligand on cytotoxic T lymphocytes to the Fas receptor on hepatocytes is also known to induce apoptosis. The aim of this study was to clarify changes of cytokines in patients with liver cirrhosis (LC) and advanced hepatocellular carcinoma (aHCC) receiving intra-arterial combination chemotherapy. Twenty-one adult Japanese LC patients with aHCC received intra-arterial combination chemotherapy. The serum levels of TNF-alpha, soluble TNF receptor-I (sTNFr-I), soluble Fas ligand (sFas L), and soluble Fas (sFas) were evaluated. Thirteen of the 21 patients (group R) showed an objective response, while the other eight patients (group N) showed no response. The serum level of TNF-alpha was lower after chemotherapy than before chemotherapy in group N, but there was no difference of serum sTNFr-I levels between before and after chemotherapy and there were also no differences between the two groups. The serum sFas levels were higher after chemotherapy than before chemotherapy in group N, while there was no difference among groups. These results indicate that a high serum TNF-alpha level and a low serum sFas level might be important for successful combined arterial chemotherapy in LC patients with aHCC.