Hepatic arterial infusion chemotherapy for hepatocellular carcinoma with portal vein tumor thrombosis

AIM: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with poor prognosis. The aim of this prospective study was to evaluate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for patients with this disease. METHODS: Eighteen HCC patients with PVTT were treated with HAIC via a subcutaneously implanted injection port. A course of chemotherapy consisted of daily cisplatin (10 mg for one hour) followed by 5-fluorouracil (250 mg for five hours) for five continuous days within a given week. The patients were scheduled to receive four consecutive courses of HAIC. Responders were defined in whom either a complete or partial response was achieved, while non-responders were defined based on stable or progressive disease status. The prognostic factors associated with survival after treatment were analyzed. RESULTS: Six patients exhibited partial response to this form of HAIC (response rate=33%). The 3, 6, 9, 12 and 18-month cumulative survival rates for the 18 patients were 83%, 72%, 50%, 28%, and 7%, respectively. Median survival times for the six responders and 12 non-responders were 15.0 (range, 11-18) and 7.5 (range, 1-13) months, respectively. It was demonstrated by both univariate and multivariate analyses that the therapeutic response and hepatic reserve function were significant prognostic factors. CONCLUSION: HAIC using low-dose cisplatin and 5-fluorouracil may be a useful alternative for the treatment of patients with advanced HCC complicated with PVTT. There may also be survival-related benefits associated with HAIC.     

Efficacy of iron chelator deferoxamine for hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma patients refractory to current treatments

The prognosis of advanced hepatocellular carcinoma (HCC) remains poor. For patients with advanced HCC, the multikinase inhibitor sorafenib is recommended as the current standard of care. In contrast, hepatic arterial infusion chemotherapy (HAIC) is one of the recommended treatments in Japan. However, in Japan, the use of sorafenib versus hepatic arterial infusion chemotherapy for first-line treatment remains unclear, because there have been no randomized controlled trials comparing HAIC with sorafenib. HAIC can substantially prolong survival in patients with complete and partial response, while non-responders may be suitable candidates for sorafenib therapy. Nonetheless, HAIC non-responders with deteriorated liver function currently have no treatment options. We have shown the efficacy of an alternative therapy, the iron chelator deferoxamine, for advanced HCC patients with deteriorated liver function. Iron chelators may have future therapeutic possibilities in this patient population.     

External beam radiation therapy for inoperable hepatocellular carcinoma with portal vein thrombosis

Portal vein thrombosis (PVT) in patients with hepatocellular carcinoma (HCC) has a poor impact on prognosis. Many of these tumors may cause intrahepatic and extrahepatic metastases. From January 1991 to December 1996, 41 unresectable HCC patients with PVT underwent transcatheter arterial chemoembolization (TACE) and external beam radiation therapy (EBRT) to the portion of PVT. The irradiated field, with a mean equivalent field size of 6.6 x 7.1 cm2, was localized and simulated by abdominal sonography, angiography and computed tomography. Radiation dose ranged from 36 to 66 Gy (mean dose: 51.4 Gy), in a daily fraction of 1.8 to 2 Gy. The response of EBRT was evaluated by abdominal sonography within 3 months of completion of EBRT. The response rates of the PVT after treatment were 39% for complete response (CR), 41% for partial response (PR), and 19% for no response (NR), respectively. The median overall survival time from start of radiotherapy was 10 months for all patients, 17 months for CR patients, 8 months for PR patients and 4 months for NR patients. By multivariate analysis, response of PVT resulted in a significant improvement in survival. (P = 0.001) There was no occurrence of severe complication of radiation-induced liver disease. The results obtained with combined treatment modality of EBRT and TACE in the treatment of HCC patients with PVT are encouraging.     

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. METHODS: Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m 2 epirubicin on day 1, 60 mg/m 2 cisplatin for 2 h on day 2, and 500 mg/m 2 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. RESULTS: Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD).The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm 3 (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-Ⅱ (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. CONCLUSION: HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm 3 and good prognostic factors.     

Hepatic arterial infusion chemotherapy using 5-fluorouracil and systemic interferon-α for advanced hepatocellular carcinoma in combination with or without three-dimensional conformal radiotherapy to venous tumor thrombosis in hepatic vein or inferior vena cava

Aim: We investigated the efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5‐fluorouracil (5‐FU) and systemic interferon (IFN)‐α (HAIC‐5‐FU/IFN) for advanced hepatocellular carcinoma (HCC) with venous tumor thrombosis (VTT) in the hepatic vein trunk (Vv2) or inferior vena cava (Vv3). Methods: Thirty‐three patients with HCC/Vv2/3 underwent HAIC with 5‐FU (500 mg/body weight/day, into hepatic artery on days 1–5 on the first and second weeks) and IFN‐α (recombinant IFN‐α‐2b 3 000 000 U or natural IFN‐α 5 000 000 U, intramuscularly on days 1, 3 and 5 of each week). Three‐dimensional conformal radiotherapy (3D‐CRT) was used in combination with HAIC‐5‐FU/IFN in 14 of 33 patients to reduce VTT. Result: The median survival time (MST) was 7.9 months, and 1‐ and 2‐year survival rates were 30% and 20%, respectively. Evaluation of intrahepatic response after two cycles of HAIC‐5‐FU/IFN showed complete response (CR) in three (9%) and partial response (PR) in seven (21%), with an objective response rate of 30%. Multivariate analysis identified reduction of VTT (P = 0.0006), size of largest tumor (P = 0.013) and intrahepatic response CR/PR (P = 0.030) as determinants of survival. CR/PR correlated significantly with tumor liver occupying rate (P = 0.016) and hepatitis C virus Ab (P = 0.010). Reduction of VTT correlated significantly with radiotherapy (P = 0.021) and platelet count (P = 0.015). Radiotherapy‐related reduction in VTT significantly improved survival of 16 patients with Vv3 and non‐CR/PR response of HAIC‐5‐FU/IFN (P = 0.028). Conclusion: As for advanced HCC with VTT of Vv2/3, HAIC‐5‐FU/IFN responsive patients could obtain favorable survival. Despite ineffective HAIC‐5‐FU/IFN, the combination with effective radiotherapy to VTT might improve patients' prognosis.     

Pathological Complete Remission of Advanced Hepatocellular Carcinoma with Main Portal Vein Tumor Thrombosis by Hepatic Arterial Infusion Chemotherapy

Cures for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) are rare and difficult. We report a case of pathologically confirmed complete remission of HCC induced by hepatic arterial infusion chemotherapy (HAIC). A 45-year-old male patient had a massive HCC in the right lobe of the liver and tumor thrombus in the right and main portal veins. He achieved a partial response after two cycles of HAIC with 5-fluorouracil (750 mg/m²) and cisplatin (25 mg/m²). After the completion of six cycles he received a curative partial hepatectomy, and histopathology revealed complete necrosis without any viable tumor cell. He was in good health at a 4-month follow-up. These results suggest that this regimen is a promising therapeutic modality for the treatment of advanced HCC with PVTT.     

Serum vascular endothelial growth factor as a predictor of response and survival in patients with advanced hepatocellular carcinoma undergoing hepatic arterial infusion chemotherapy

Background

Hepatic arterial infusion chemotherapy (HAIC) has been recognized as a useful therapeutic modality for patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to investigate the association between serum vascular endothelial growth factor (VEGF) levels and the therapeutic effect of HAIC and the survival of patients undergoing HAIC.

Methods

Seventy-one patients with advanced HCC underwent HAIC through a subcutaneously implanted infusion port. One chemotherapy course consisted of low-dose cisplatin (10?mg/body on days 1–5) and 5-fluorouracil (250?mg/body on days 1–5), and 1 treatment cycle consisted of 2–3 courses of chemotherapy. Serum VEGF levels were measured with the Bio-Plex Suspension Array System (Bio-Rad Laboratories).

Results

The median survival time (MST) of all patients was 10.2?months, and the 1-, 2-, 3-, and 5-year survival rates were 46.5, 21.9, 12.8, and 3.7%, respectively. Of the 71 patients, 3 achieved a complete response (CR) and 22 achieved a partial response (PR) [response rate (CR?+?PR/71)?=?35%]. The serum VEGF level (≥100?pg/mL, P?=?0.026) was an independent predictor of therapeutic effect, and was positively correlated with the platelet count (r?=?0.569, P?r?=?0.543, P?P?=?0.046), serum VEGF level (P?=?0.004), and therapeutic effect (P?=?0.005) were identified by multivariate analysis as independent predictors of survival.

Conclusions

These results demonstrate that the serum VEGF level in patients with advanced HCC undergoing HAIC is an important predictive factor for therapeutic effect and survival.     

5-fluorouracil continuous infusion combined with cisplatin for advanced pancreatic cancer: a Japanese Cooperative Study

BACKGROUND/AIMS: The prognosis of patients with advanced pancreatic cancer is extremely poor. To improve their prognosis, providing effective chemotherapy is necessary. The aim of this study was to evaluate the anti-tumor activity and toxicity of combined chemotherapy (FP therapy) using 5-fluorouracil and cisplatin in Japanese chemo-naive patients with advanced pancreatic cancer. METHODOLOGY: Thirty-seven previously untreated patients with histologically proven pancreatic adenocarcinoma were treated with FP therapy. 5-fluorouracil was administered at 500 mg/m2/day by continuous intravenous infusion for 5 days and cisplatin was administered at 80 mg/m2 intravenously on the 1st day. Therapy was repeated every 4 weeks until there was evidence of disease progression or unacceptable toxicity. RESULTS: Three patients achieved partial responses, whereas none exhibited a complete response. The overall response rate was 8% (95% confidence interval, 2-22%) and the response durations were 6, 9 and 12 months, respectively. The median survival time of patients was 5 months. Toxicities were generally mild and acceptable, although nausea/vomiting was the most commonly observed toxicity. CONCLUSIONS: FP therapy on this schedule had limited anti-tumor activity for pancreatic cancer, indicating that, practically, it should not be performed in Japanese patients with advanced pancreatic cancer.     

Palliative ethanol injections of unresectable advanced esophageal carcinoma combined with chemoradiation

Combined chemoradiation therapy has proven to be an effective treatment for unresectable esophageal cancer. Nonsurgical endoscopic palliation of local disease has become feasible with neodymium:yttrium-aluminum-garnet laser, BICAP tumor probe, and metallic stents. Alternatively, endoscopic injections of ethanol are safe, inexpensive, and useful for palliation of malignant dysphagia. Two patients with unresectable squamous cell carcinoma of the esophagus were treated with 1 mL of absolute (95 g/L) alcohol injections once a week for 4 weeks, followed by chemoradiation therapy consisting of concomitant 5-fluorouracil 300 mg/m/d and radiation therapy (total of 60 Gy over 6 weeks). One patient had a complete response but died of alcoholism 25 months after diagnosis without evidence of tumor recurrence. The other patient had a partial response but died 16 months after diagnosis from disease progression. We conclude that tumor ablation by ethanol injection for palliation combined with chemoradiation may be a low-cost alternative for advanced unresectable esophageal cancer.     

Lenalidomide induced therapeutic response in a patient with aggressive multi-system Langerhans cell histiocytosis resistant to 2-chloro-deoxyadenosine and early relapsing after high-dose BEAM chemotherapy with autologous peripheral blood stem cell transplantation

Adult Langerhans cell histiocytosis (LCH) usually follows a favorable course. Very rarely, however, multi-system (multi-organ) LCH difficult to manage either with traditional first line treatment (vinblastine, mercaptopurine, prednisone or etoposide) or 2-chlorodeoxyadenosine occurs. In these patients, other treatment modalities have to be used. We describe a patient with LCH manifesting with generalized lymphadenopathy and infiltrating the pulmonary parenchyma and skin. The disease activity was always associated with B-symptoms (weight loss, subfebrile states, night sweats). Histological investigations repeatedly showed higher proliferation activity than that usual in adult patients with LCH. Expression of Ki-67 proliferation marker was up to 30% and there were 8-10 cells in mitosis in the microscope viewing field. Therefore, therapy started with the application of stimulation regimen (cyclophosphamide 2 g/m2 on day 1 and etoposide 200 mg/m2 on days 1-3) followed by collection of peripheral blood stem cells. Then, treatment with 2-chlorodeoxyadenosine, the first 3 cycles as monotherapy of 5 mg/m2 SC on days 1-5 in 28-day cycles, the next 3 cycles in combination with cyclophosphamide 150 mg/m2 on days 1-5 and methylprednisolone 250 mg on days 1-5, was used. However, the disease relapsed 2 months after completion of the therapy. This early relapse was treated with 4 cycles of CHOEP chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone). Following the 4th cycle of CHOEP, high-dose BEAM chemotherapy (carmustine, etoposide, cytarabine, melphalan) with autologous stem cell transplantation were administered. According to the follow-up PET-CT examination, this treatment resulted in complete disease remission. However, the disease relapsed again in the lymph nodes, lungs, skin and bones 5 months after the high-dose chemotherapy. The progression was documented on PET-CT scanning. Lenalidomide 25 mg daily for 21 days in 28-day cycles with dexamethasone 20 mg once a week were administered as the 4th line treatment. After the 4th cycle of lenalidomide, PET-CT was performed, where the CT component suggested a significant reduction (more than 50%) in the size of the lymph nodes and the PET component showed substantial reduction in fluorodeoxyglucose accumulation in the affected lymph nodes as well as in the bone lesions. HRCT showed disappearance of pulmonary nodules. During the treatment, CRP levels declined and hemoglobin rose from 110 to 141 g/l, i.e. partial remission was achieved after 4 cycles. Etoposide (100 mg IV) was added to lenalidomide and dexamethasone on days 22, 23 and 24 of the above mentioned 28-day cycle. The added etoposide further intensified treatment response. In all, 11 cycles of this chemotherapy were given, resulting in complete remission confirmed by follow-up PET-CT. The achieved remission was consolidated using allogeneic bone marrow transplantation after FLAMSA reduced intensity conditioning without amsacrine. Four months after allogeneic transplantation, the patient has been relapse free. Herein we presented treatment response of highly aggressive LCH to lenalidomide. The used four cycles led to partial remission only and with the combination of lenalidomide, dexamethasone and etoposide the treatment response was further intensified to complete remission.     

Advanced ovarian cancer: long-term results of treatment with intensive cisplatin-based chemotherapy of brief duration

Study Objective: To determine the efficacy of a 6-month course of combination chemotherapy with hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin (H-CAP) in the treatment of advanced ovarian carcinoma. Design: Prospective, non-randomized, single-institution trial with a 6-month course of chemotherapy, followed by second-look laparotomy for restaging. Minimum follow-up after completion of therapy is 83 months. Patients: Fifty-five patients with advanced (stage III or IV), intermediate- or high-grade epithelial carcinoma of the ovary. Twenty patients had limited residual tumor (3 cm or less maximal tumor diameter) after initial cytoreductive surgery; 35 had extensive residual disease. Interventions: All patients received chemotherapy with hexamethylmelamine (150 mg/m2 body surface area orally on days 1 to 14), cyclophosphamide (350 mg/m2 intravenously on days 1 and 8), doxorubicin (20 mg/m2 intravenously on days 1 and 8), and cisplatin (60 mg/m2 intravenously on day 1). Courses were repeated at 4-week intervals; 41 patients (75%) received six courses; 10 patients received five courses, 3 patients received four courses, and 1 patients received three courses. Forty-seven patients underwent second-look laparotomy after completion of therapy; 8 had their disease restaged clinically. Results: Fifty-three of fifty-five patients (96%) had either partial or complete response to treatment. Nineteen of forty-seven patients who had a second-look laparotomy had a surgically documented complete response; 17 of these 19 patients began chemotherapy with limited residual tumor. Ten patients (18%) remain disease-free 83 to 108 months after therapy, whereas three additional patients died of other diseases without clinical evidence of recurrent ovarian cancer. Nine of twenty patients who began chemotherapy with limited residual tumor remain disease-free, as compared to only 1 of 35 patients with more extensive tumor (P less than 0.001). All long-term, disease-free survivors had surgically documented complete response at second-look laparotomy. Conclusions: Treatment with cisplatin-based combination chemotherapy after aggressive cytoreductive surgery should be considered standard treatment for advanced ovarian carcinoma. Our intensive, 6-month course of treatment produced results comparable to those previously reported with prolonged treatment.     

Gemcitabine plus S-1 combination therapy (GS therapy) for pancreatic cancer patients with high-grade hepatic metastasis

Pancreatic cancer shows the worst prognosis among the solid tumors, and survival for patients with high-grade liver metastasis is estimated at around a few months. We reported the effects of combination therapy with gemcitabine and S-1 (GS therapy) on pancreatic cancer patients with high-grade hepatic metastasis. Patients with severe metastatic pancreatic cancer received chemotherapy comprising S-1 (30mg/m2 p.o. b.i.d., days 1-14) and gemcitabine (1000mg/m2 on days 1 and 8), repeated every 3 weeks. Fourteen patients (7 men, 7 women) received treatment at a mean age of 56.5 years (range, 39-76 years), achieving complete response in 1 patient, partial response in 5 patients, and stable disease in 3 patients and progressive disease in 5 patients. The response rate was thus 43%. Median progression-free survival was 186 days (95% confidence interval, 40-247 days). Median overall survival was 261 days (95% confidence interval, 162-358 days). GS therapy appears to be well-tolerated and effective in patients with high-grade hepatic metastasis.     

Primary treatment with pulsed melphalan, dexamethasone and thalidomide for elderly symptomatic patients with multiple myeloma

Fifty patients with multiple myeloma >or=75 years of age received primary treatment with melphalan (M) 8 mg/m(2) on days 1-4, dexamethasone (D) 12 mg/m2 on days 1-4 and 17-20 and thalidomide (T) 300 mg at bedtime on days 1-4 and 17-20. This regimen was repeated every 5 weeks for three courses. Patients without evidence of disease progression received nine additional courses of MDT, but without DT on days 17-20, every 5 weeks. Sixty-two percent of patients achieved a partial response and 10% a complete response. The median time to response was 2 months. The median time to progression for all patients was 21.2 months. Deep venous thrombosis and peripheral neuropathy each occurred in 9% of patients.     

Adjuvant hepatic arterial infusion chemotherapy after radical hepatectomy for hepatocellular carcinoma--results of long-term follow-up.

BACKGROUND/AIMS: This clinical study aimed to clarify the effectiveness and indication of adjuvant hepatic arterial infusion chemotherapy (HAIC) that is performed to prevent recurrence after radical hepatectomy for hepatocellular carcinoma (HCC). METHODOLOGY: From January 1986 to December 1992, 135 HCC patients, who tolerated curative hepatic resection in which all of the macroscopic HCC was removed, were included in this study. They were divided into two groups. One group was comprised of 68 patients who received HAIC after radical hepatectomy (HAIC (+) group), and the other group was comprised of 67 patients who received radical hepatectomy alone (HAIC (-) group). In the HAIC (+) group, an emulsion of doxorubicin (30-50 mg) and lipiodol (3-5 ml) was injected from a reservoir every 2 or 3 months for 1 year. RESULTS: The cumulative survival rates in the HAIC (+) group (79.1%, 54.5% and 39.9% at 3, 5, and 7 years after hepatectomy, respectively) were better than those in the HAIC (-) group (69.2%, 38.1% and 26.8%, respectively) (p = 0.086). The disease-free survival rates in the HAIC (+) group (50.8%, 31.7% and 25.6% at 3, 5, and 7 years after hepatectomy, respectively) were significantly better than those in the HAIC (-) group (25.7%, 20.6% and 6.4%, respectively) (p = 0.006). This improvement was evident for 3 years after hepatectomy. The adjuvant HAIC was effective especially in patients with good liver function, whose tumor size ranged between 2.1 cm and 5 cm in diameter, and who received a minor hepatic resection. CONCLUSIONS: Adjuvant HAIC was effective in preventing recurrence after radical hepatectomy for HCC. This treatment is especially indicated for patients with good liver function, whose tumor size ranges between 2.1 cm and 5 cm in diameter, and who have received a minor hepatic resection.     

Salvage chemotherapy with IAPVP-16 for advanced refractory or relapsed follicular lymphomas.

BACKGROUND AND OBJECTIVE: Patients with follicular lymphoma (FL) who do not respond to first-line chemotherapy or those who relapse after obtaining a remission have a poor outcome with standard treatment. In an effort to obtain a high rate of responses we designed an intensive brief duration salvage chemotherapy regimen. DESIGN AND METHODS: Forty-four consecutive patients with advanced follicular lymphoma were treated. Nine had primary refractory disease, 13 had achieved a partial remission, 16 were in untreated relapse or progression and six were in chemosensitive relapse. The IAPVP-16 regimen consists in ifosfamide 5 g/m(2) iv on day 1, etoposide 100 mg/m(2) iv on days 1-3, Ara-C 1.2 g/m(2)/12 hours iv on days 1-2 and methylprednisolone, 80 mg/m(2) iv on days 1-5. Granulocyte colony-stimulating factor was used from day 6 in 68 of 114 courses. RESULTS: Eighteen patients (41%) achieved a complete remission and 17 (39%) a partial remission, for an overall response rate of 80%. There were no treatment-related deaths. All treatment courses were followed by severe neutropenia, and 66% also by severe thrombocytopenia, but there were no serious hemorrhagic events. Neutropenic fever occurred in 56% of the courses with only four severe infections. Non-hematologic toxicity was modest. Twenty-eight patients proceeded to a stem cell transplantation. After a median follow-up of 25 months (range 4-95), the median progression-free survival and overall survival are 32 and 58 months, respectively. The median PFS was 33 months for responders and 11 months for non-responders (p=0.05), while the median OS has not been reached in responders and is 23 months in non-responders (p=0.0005). INTERPRETATION AND CONCLUSIONS:. The IAPVP-16 regimen is an effective and well tolerated treatment for advanced FL, allowing most eligible patients to proceed with significant tumor reduction to high-dose therapy and SCT.     

Complete response to short‐term sorafenib treatment alone for hepatocellular carcinoma with bone,lymph node,and peritoneum metastases

We report a 60‐year‐old male patient who developed extrahepatic metastases in bone, peritoneum, and lymph nodes (confirmed by computed tomography and positron emission tomography–computed tomography) after hepatectomy for hepatocellular carcinoma. He was treated with sorafenib (800 mg/day) but developed grade 3 hand–foot syndrome. He continued to be treated with sorafenib but at a lower dose (400 mg/week). The response to sorafenib therapy was graded as complete response at 6 months by the Response Evaluation Criteria in Solid Tumors. Sorafenib was continued for 8 months and the patient remained in complete response for 11 months. Further reporting of similar cases should help design treatment strategies and evaluate predictors of the response to sorafenib therapy.     

Phase II study of cisplatin, epirubicin and continuous infusion of 5-fluorouracil in patients with advanced intrahepatic cholangiocellular carcinoma (ICC)

BACKGROUND/AIMS: To clarify the efficacy and toxicity of cisplatin, epirubicin, and continuous infusion of 5-FU (CEF therapy) in patients with advanced intrahepatic cholangiocellular carcinoma (ICC). METHODOLOGY: Chemo-na?ve patients with advanced ICC were treated with cisplatin at 80 mg/m2 and epirubicin at 50 mg/m2 on day 1, and continuous infusion of 5-FU at 500 mg/m2/day on days 1 through 5. If there was no evidence of tumor progression or unacceptable toxicity, the treatment was repeated every 4 weeks, up to a maximum of 6 courses. RESULTS: Thirty-nine patients were enrolled in this study. The median number of courses was 2 (range, 1-6). A partial response was obtained in 4 patients (10%) with a median duration of 2.3 months. Twenty-seven patients (69%) showed no change, and 7 patients (18%) had progressive disease. The median survival time was 9.1 months and the 1-year survival rate was 23%. The progression-free survival time was 5.1 months. Grade 3 to 4 adverse effects were leukocytopenia (51%), neutropenia (74%), thrombocytopenia (23%), and nausea/vomiting (10%). Most of the toxicities were reversible, but 2 patients died of neutropenic sepsis. CONCLUSIONS: CEF therapy has marginal antitumor activity against advanced ICC, although hematological toxicity is the major and most frequent toxicity.     

Treatment strategies for advanced hepatocellular carcinoma: Sorafenib vs hepatic arterial infusion chemotherapy

Sorafenib is used worldwide as a first-line standardsystemic agent for advanced hepatocellular carcinoma(HCC) on the basis of the results of two large-scale Phase Ⅲ trials. Conversely,hepatic arterial infusion chemotherapy(HAIC) is one of the most recommended treatments in Japan. Although there have been no randomized controlled trials comparing sorafenib with HAIC,several retrospective analyses have shown no significant differences in survival between the two therapies. Outcomes are favorable for HCC patients exhibiting macroscopic vascular invasion when treated with HAIC rather than sorafenib,whereas in HCC patients exhibiting extrahepatic spread or resistance to transcatheter arterial chemoembolization,good outcomes are achieved by treatment with sorafenib rather than HAIC. Additionally,sorafenib is generally used to treat patients with Child-Pugh A,while HAIC is indicated for those with either Child-Pugh A or B. Based on these findings,we reviewed treatment strategies for advanced HCC. We propose that sorafenib might be used as a first-line treatment for advanced HCC patients without macroscopic vascular invasion or Child-Pugh A,while HAIC is recommended for those with macroscopic vascular invasion or Child-Pugh A or B. Additional research is required to determine the best second-line treatment for HAIC non-responders with Child-Pugh B through future clinical trials.     

特异性肿瘤细胞毒T淋巴细胞联合肝动脉插管化疗治疗晚期肝细胞癌前瞻性研究

本文采用对照和随机的方法,前瞻性地研究了特异性肿瘤细胞毒T淋巴细胞(CTLs)加肝动脉化疗(HAIC)联合疗法和单一CTLs疗法及单一HAIC疗法三者在治疗晚期肝细胞癌中的作用。160例诊断为晚期肝细胞癌患者经随机分为A、B和C三组。A组用CTLs加HAIC联合疗法治疗;B组予单一CTLs疗法;C组接受单一HAIC治疗。研究结果提示,联合疗法的总缓解率(完全反应+部分反应)和1、2、3年的生存率均比任何单一治疗组高(P<0.05)。因此,CTLs加HAIC联合疗法可能是治疗晚期肝细胞癌病人有希望的治疗手段。     

硼替佐米联合化疗治疗10例多发性骨髓瘤

目的:观察硼替佐米联合化疗药物治疗初治、复发难治多发性骨髓瘤(MM)的疗效及安全性。方法:5例初治MM患者在每一疗程的第1、4、8、11天静脉注射硼替佐米0.7～1.3mg/m2,每3周为一疗程;每2个疗程(6周)的第1～4天,口服美法仑9mg/(m2·d)和泼尼松60mg/(m2·d);每例患者至少接受2～10个疗程。5例复发难治患者,在每3周1个疗程,第1、8天分别静脉注射硼替佐米3.5mg,或第1、4、8、11天1.0～1.3mg/m2。每次用硼替佐米前静脉注射地塞米松40mg;每例患者至少接受1～6个疗程。采用Blade标准评价疗效,按照美国国立癌症研究所(NCI)(第3版)判断不良反应。结果:中位随访8个月,5例初治患者中2例完全缓解(CR),1例接近完全缓解(nCR),1例部分缓解(PR),1例轻微反应(MR)。5例复发难治患者中,2例nCR,2例MR,1例无改变(NC)。主要不良反应包括胃肠道症状、不同程度的血小板减少、周围神经症状和乏力等。经对症治疗及调整用药剂量后均能改善。结论:硼替佐米对于初治或复发难治的MM患者,是一种可以耐受的、疗效确切的新的治疗选择。