levoleucovorin and Cholangiocarcinoma

Cholangiocarcinoma is a rare malignancy with a poor prognosis. The majority of tumors present at an advanced stage, and relapse often occurs after surgery conducted with curative intent. In both of these cases, standard treatment is a combination of cisplatin and gemcitabine. The use of folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX) in second-line treatment improves survival, but outcomes remain dismal. Studies have shown that cholangiocarcinoma possesses a wide spectrum of genetic aberrations. Clinical trials evaluating targeted therapies in patients with FGFR2 fusions, IDH1 mutations, and BRAF mutations have yielded very promising results, and the agents were generally well tolerated. Several FGFR2 fusion-targeted agents have achieved response rates between 20.7% and 35.5%, with disease stability rates ranging between 76% and 82%. Agents targeting FGFR2 fusions also have produced median progression-free survival (PFS) ranging from 5.7 to 6.9 months and median overall survival (OS) ranging from 12.5 to 21.1 months. Ivosidenib in patients with an IDH1/2 mutation has produced a response rate of 2% and a disease stability rate of 51%, with median PFS of 2.7 months and median OS of 10.8 months. In patients with a BRAF mutation, a combination of dabrafenib and trametinib led to an overall response rate of 51% and disease stability in another 40% of patients. Median PFS and OS were 9 and 14 months, respectively. Patients should be encouraged to participate in clinical trials.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cholangiocarcinoma; Cisplatin; Deoxycytidine; Disease-Free Survival; Fluorouracil; Gemcitabine; Humans; Leucovorin; Mutation; Oncogene Proteins, Fusion; Organoplatinum Compounds; Survival Rate

The term of biliary tract cancer (BTC) refers to all tumors that arise from the biliary tract or the biliary drainage system, including the intra- and extra-hepatic bile ducts as well as the gallbladder. BTCs are aggressive tumors with limited treatment options and poor overall survival. Currently, surgery remains to be the only potentially curative treatment, and most patients develop recurrence. For advanced tumors, only limited effective treatment modalities exist today. Gemcitabine plus cisplatin is considered as a standard option for advanced biliary cancer. A randomized phase III trial (ABC-02 trial) showed superiority of gemcitabine plus cisplatin over gemcitabine alone. In that study, they showed that after a median follow-up of 8.2 months, the median overall survival was 8.1 months in the gemcitabine-only group and 11.7 months in the gemcitabine plus cisplatin group (p<0.001). However, while this is a definite advancement, a 3-month survival extension among patients with BTC is modest at best. Moreover, this regimen has not been compared head-to-head with other gemcitabine based combinations. Gemcitabine monotherapy, 5-fluorouracil plus leucovorin, and single-agent capecitabine are all reasonable options for patients with a borderline performance status. Recent advancements have provided new insight into the genomic landscape of BTCs, and thus, it remains unclear whether combined treatment with molecular targeted agents or other cytotoxic chemotherapeutic agents may also be effective against advanced BTC.

Topics: Antineoplastic Agents; Bevacizumab; Biliary Tract Neoplasms; Cholangiocarcinoma; Cisplatin; Deoxycytidine; Erlotinib Hydrochloride; Fluorouracil; Gemcitabine; Humans; Leucovorin

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cholangiocarcinoma; Cisplatin; Deoxycytidine; Fluorouracil; Gemcitabine; Humans; Leucovorin

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

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Catheterization; Catheters; Cholangiocarcinoma; Disease Progression; Equipment Failure; Female; Fluorouracil; Hepatic Artery; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Withholding Treatment

Gemcitabine has broad activity in a variety of solid tumors including biliary tract carcinomas. The authors evaluated 6-month survival, response, and toxicity associated with a combination of gemcitabine, 5-fluorouracil (5-FU), and leucovorin (LV) in patients with unresectable or metastatic biliary tract or gallbladder adenocarcinoma (ACA).. A 4-week course included 1000 mg/m2 gemcitabine by intravenous infusion over 30 minutes on Days 1, 8, and 15, 25 mg/m2 LV by intravenous push, and 600 mg/m2 5-FU by intravenous push after LV.. Forty-two patients were enrolled in 6 months, 35 of whom had metastatic disease. Patients with biliary tract ACA included 24 with hepatic disease (19 patients had intrahepatic disease and 5 patients had extrahepatic disease) and 4 with disease in the ampulla of Vater. All patients were evaluable and received a median of 4 courses of treatment (range, 1-21 courses). Commonly occurring severe toxicity (NCI CTC Grade 3 or worse) included: dyspnea (four patients), nausea (four patients), fatigue (seven patients), thrombocytopenia (six patients), emesis (four patients), and diarrhea (four patients). Five partial responses (9.5%) occurred, 3 of which were sustained for > or = 8 weeks. No treatment-related deaths occurred. Thirty-two patients had disease progression and 38 died after a median follow-up of 20 months (range, 1.4-24 months). The median time to disease progression was 4.6 months (95% confidence interval [95% CI], 2.4-6.6%). The median survival period was 9.7 months (95% CI, 7-12%).. This combination regimen was manageable in patients with advanced biliary tract and gallbladder ACA. Of 42 patients, 24 (57%) survived > or = 6 months, satisfying the primary end point of the trial. The length of survival suggested that gemcitabine, 5-FU, and LV had benefit equivalent to gemcitabine alone.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cholangiocarcinoma; Deoxycytidine; Female; Fluorouracil; Gallbladder Neoplasms; Gemcitabine; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Male; Middle Aged; Survival Analysis

Mitomycin C (MMC) in combination with infusional 5-fluorouracil (FU) plus folinic acid (FA) is an effective treatment for metastatic gastrointestinal cancer. Anthracyclines are commonly used in the treatment of upper gastrointestinal cancer. The aim of this study was to determine the maximum tolerated dose of liposomal, pegylated doxorubicin (Caelyx) in combination with infusional 5-FU/sodium FA and MMC. Escalating doses of Caelyx (15-25-30-35 mg m(-2) corresponding to dose levels I-IV) were applied on days 1 and 29, given to fixed doses of 24-h 5-FU (2000 mg m(-2)) and sodium FA (500 mg m(-2), mixed with 5-FU in one pump) weekly for 6 weeks, and MMC 7 mg m(-2) on days 8 and 36. At least three patients were treated at each dose level. A total of 25 patients are evaluable. No dose-limiting toxicity (DLT) was observed on level I (n=3). On level II, DLT occurred in three out of five patients (mucositis and leucopenia). Owing to the early DLTs at this dose, we added a 20 mg m(-2) Caelyx dose level (Ia). In total, 17 patients were treated at this dose level. Among these, only two patients experienced DLT in cycle one and 37 complete cycles have been administered in association with a low toxicity profile. The median dose intensity was 100% for each drug during the first course and no treatment delay exceeding 7 days was required. The recommended dose of 4-weekly Caelyx in combination with weekly 24-h 5-FU/sodium FA and 4-weekly MMC is 20 mg m(-2). Preliminary antitumour activity has been observed in patients with pretreated pancreatic cancer and in untreated gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cholangiocarcinoma; Doxorubicin; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liposomes; Male; Maximum Tolerated Dose; Middle Aged; Mitomycin; Pancreatic Neoplasms; Stomach Neoplasms; Survival Analysis; Treatment Outcome

Unresectable biliary tract carcinoma (BTC) is associated with a very poor prognosis. To improve efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in BTC, we designed a new therapeutic schedule, the LV5FU2-P regimen.. Twenty-nine patients with advanced or metastatic BTC were prospectively enrolled in the study. The treatment (LV5FU2-P regimen) consisted of a biweekly administration of a 2-h infusion of leucovorin 200 mg/m(2), a 400 mg/m(2) bolus of 5-FU followed by a 22-h continuous infusion of 600 mg/m(2) 5-FU on two consecutive days and cisplatin 50 mg/m(2) on day 2. Clinical symptoms, performance and weight changes were monitored.. Objective responses were observed in 10 patients (34%) (95% confidence interval 23% to 45%) including one complete response and nine partial responses (stabilization 38%, progression 28%). Median progression-free survival and overall survival were 6.5 and 9.5 months, respectively. Weight gain was observed in 45% of patients and performance status improved in 60%. One patient had a grade 4 thrombocytopenia, and grade 3 toxicity occurred in 41% of patients. There were no treatment-related deaths.. This study, one of the largest phase II trials performed for this disease, shows that the LV5FU2-P regimen is an active and well-tolerated chemotherapy for advanced and metastatic BTC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cholangiocarcinoma; Cisplatin; Female; Fluorouracil; Gastrointestinal Diseases; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Prospective Studies; Survival Rate; Thrombocytopenia; Treatment Outcome

We have reported a 33% partial response rate with acceptable toxicity using weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in patients with far advanced biliary tract cancers (BTC). In this study, we added mitomycin (MMC) to 5-FU and LV in an attempt to improve the response rate and survival. From July 1997 to September 1999, 25 chemotherapy-naive patients with pathology-proven far advanced BTC and periampullar cancers were enrolled. The regimen consisted of MMC 10 mg/m(2) every 8 weeks combined with 5-FU 2600 mg/m(2) and LV 150 mg at a schedule of 24-h infusion weekly for 6 weeks followed by a 2 week break. There were 10 males and 15 females with a median age of 57 years (range 40-76). The sites of primary tumor were 15 intrahepatic cholangiocarcinomas (CC), one perihilar CCs, three distal BTC, three gallbladder cancers (GB) and three periampullar cancers. A total of 148 sessions of chemotherapy were given with a mean of 8 (range 2-18). Nineteen patients were evaluable for response. The response rate was: 26% (five of 19) partial response, 42% (eight of 19) stable disease and 32% (six of 19) progressive disease. All of the patients were evaluable for toxicity. Toxicities more than grade III-IV were thrombocytopenia 16% (four of 25), leukopenia 12% (three of 25) and vomiting 4% (one of 25). There were four treatment-related deaths. The median time to disease progression was 3 months. The median survival was 6 months. A combination of MMC with weekly high-dose 5-FU and LV in patients with BTC did not improve the response rate, but produced more toxicity than weekly high-dose 5-FU and LV alone.

Topics: Adenocarcinoma; Adult; Aged; Ampulla of Vater; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cholangiocarcinoma; Digestive System Neoplasms; Disease Progression; Drug Administration Schedule; Female; Fluorouracil; Hematologic Diseases; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Mitomycin; Survival Rate; Treatment Outcome

Unresectable adenocarcinoma of the biliary tree are associated with a very poor prognosis. 5-fluorouracil (5-FU) combination regimens have produced objective response rates in approximately 10-20% of patients. Leucovorin increases the selective cytotoxicity of 5-FU. There also are encouraging reports of carboplatin in combination with 5-FU in other gastrointestinal tract malignancies.. Fourteen consecutive eligible patients were treated with a combination of carboplatin, 300 mg/m2, intravenously (i.v.) on Day 1 only and 5-FU, 400 mg/m2, i.v. with leucovorin, 25 mg/m2, i.v. on Days 1-4. All patients were required to have a histologically confirmed diagnosis and measurable disease. Patients were evaluated for response, survival, and toxicity.. A total of 48 cycles of therapy were delivered. The median survival was 5 months. One patient achieved complete remission and two others partial remission, for a total response rate of 21.4%. Four additional patients had stable disease for a median duration of 4 months. The therapy was well tolerated, with moderate myelosuppression as the main dose-limiting toxicity.. The current combination regimen of leucovorin-modulated 5-FU with carboplatin is well tolerated with appropriate supportive care, produces significant objective responses in 21% of patients with biliary tree carcinoma, and should be considered for the treatment of this disease.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Carboplatin; Cholangiocarcinoma; Drug Interactions; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Pancreatic Neoplasms

UFT (tegafur and uracil) has been studied extensively in Japan, with documented efficacy in hepatobiliary and pancreatic cancer. In the United States, UFT with or without leucovorin has not undergone phase II testing in these malignancies. Our current trial is designed primarily to assess the efficacy in terms of response rates to UFT with leucovorin in patients with advanced hepatobiliary and pancreatic cancer. Secondary objectives include determining response duration, time to disease progression, overall survival, quality of life, and toxicity.

Topics: Adenocarcinoma; Adult; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Cholangiocarcinoma; Drug Combinations; Humans; Leucovorin; Liver Neoplasms; Pancreatic Neoplasms; Quality of Life; Tegafur; Treatment Outcome; Uracil

Intrahepatic cholangiocarcinoma (iCCA) is a primary liver malignancy with a poor prognosis and limited treatment. Cisplatin with gemcitabine is used as the standard first-line chemotherapy regimen; however, there is still no robust evidence for second-line and successive treatments. Although preliminary evidence suggests a vital role of precision therapy or immunotherapy in a subset of patients, the gene alteration rate is relatively low. Herein, we explored the second-line and successive treatments using hepatic arterial infusion chemotherapy (HAIC) based on FOLFIRI after the failure of gemcitabine and platinum combined with target and immunotherapy in refractory CCAs.. Advanced patients with iCCAs confirmed by diagnostic pathology, who progressed at least on a gemcitabine/platinum doublet and/or other systemic chemotherapy combined with target therapy and immune checkpoint inhibitor, were included. All patients received infusional 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) via HAIC until progression or unacceptable toxicity. The primary objective was the feasibility of treatment, with secondary objectives of disease control rate (DCR) and 6-month survival rate.. A total of 9 iCCA patients treated between Dec 2020 and May 2021 were enrolled; 2 patients suffered from distant metastasis, while 7 had local lymph node metastasis and portal vein or hepatic vein invasion. HAIC was delivered as second-line therapy in 6/9 patients, while a third or successive therapy in 3/9 patients. The patients accepted an average of 2.90 ± 1.69 cycles of HAIC. The objective response rate was 22.2%; the disease control rate was 55.5% (5/9); median progression-free survival was 5 months; and 6-month survival rate was 66.7% (6/9).. Our results provide preliminary evidence that HAIC based on FOLFIRI regimen is efficient and safe in some patients progressing after previous treatment. Therefore, HAIC may be a promising and valuable complementary therapy for advanced CCAs as a second-line and successive therapy. Otherwise, the combination of HAIC with precision medicine may improve clinical benefits (clinical registration number: 2021BAT4857).

Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Cholangiocarcinoma; Cisplatin; Fluorouracil; Humans; Immune Checkpoint Inhibitors; Irinotecan; Leucovorin; Liver Neoplasms; Treatment Outcome

Cholangiocarcinoma (CCA) is a rare biliary tract cancer with a low five-year survival rate and high recurrence rate after surgical resection. Currently treatment approaches include systemic chemotherapeutics such as FOLFIRINOX, a chemotherapy regimen is a possible treatment for severe CCA cases. A limitation of this chemotherapy regimen is its toxicity to patients and adverse events. There exists a need for therapies to alleviate the toxicity of a FOLFIRINOX regimen while enhancing or not altering its anticancer properties. Cold atmospheric plasma (CAP) is a technology with a promising future as a selective cancer treatment. It is critical to know the potential interactions between CAP and adjuvant chemotherapeutics. In this study the aim is to characterize the efficacy of FOLFIRINOX and CAP in combination to understand potential synergetic effect on CCA cells. FOLFIRINOX treatment alone at the highest dose tested (53.8 µM fluorouracil, 13.7 µM Leucovorin, 5.1 µM Irinotecan, and 3.7 µM Oxaliplatin) reduced CCA cell viability to below 20% while CAP treatment alone for 7 min reduced viability to 3% (p < 0.05). An analysis of cell viability, proliferation, and cell cycle demonstrated that CAP in combination with FOLFIRINOX is more effective than either treatment alone at a lower FOLFIRINOX dose of 6.7 µM fluorouracil, 1.7 µM leucovorin, 0.6 µM irinotecan, and 0.5 µM oxaliplatin and a shorter CAP treatment of 1, 3, or 5 min. In conclusion, CAP has the potential to reduce the toxicity burden of FOLFIRINOX and warrants further investigation as an adjuvant therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Cholangiocarcinoma; Dose-Response Relationship, Drug; Drug Synergism; Fluorouracil; Humans; Irinotecan; Leucovorin; Oxaliplatin; Plasma Gases

Gemcitabine plus platinum as the first-line chemotherapy for cholangiocarcinoma (CCA) has limited efficacy. The aim of this study was to evaluate the effectiveness of modified FOLFIRINOX (mFOLFIRINOX) compared to that of gemcitabine plus oxaliplatin (Gemox) for patients with locally advanced or metastatic CCA.. From January 2016 to December 2019, consecutive patients who were diagnosed with locally advanced or metastatic CCA were treated with either mFOLFIRINOX or Gemox as a first-line chemotherapy. The main endpoint was Progression free survival (PFS). The second endpoints were Overall survival (OS), Disease control rate (DCR) and incidence of severe toxicity (grade 3-4). Tumors were evaluated at baseline and thence every 4-6 weeks. The study was designed and carried out in accordance with the principles of the declaration of Helsinki, approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine (XHEC-D-2020-154) and registered with ClinicalTrials.gov , number NCT04305288 (registration date: 12/03/2020).. Of 49 patients in this study, 27 were in the FOLFIRINOX regimen group and 22 in the Gemox regimen group. There were no significant differences between groups in baseline characteristics. The DCR was 77.8% in the mFOLFIRINOX group and 63.5% in the Gemox group. The corresponding median PFS was 9.9 months (95% confidence interval [CI], 7.3-12.4) in the mFOLFIRINOX group versus 6.4 months (95% CI,3.6-9.2, p = 0.040) in the Gemox group. The corresponding median OS was 15.7 months (95% CI, 12.5-19.0) versus 12.0 months (95% CI, 9.3-14.8, p = 0.099). Significantly more grade 3-4 vomiting occurred in the mFOLFIRINOX than the Gemox groups (7 (25.9%) vs 1 (4.5%), p = 0.044).. First-line mFOLFIRINOX offered more promising results in patients with advanced or metastatic CCA.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cholangiocarcinoma; Deoxycytidine; Female; Fluorouracil; Gemcitabine; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Oxaliplatin; Retrospective Studies

Management of advanced intrahepatic cholangiocarcinoma (iCCA) is challenging and overall survival is poor. Progress in the development of new therapeutic options for metastatic cholangiocarcinoma (CCA) has been slow; hence, to date, there are no approved second-line agents in this setting. Although the development of immune checkpoint inhibitors has significantly improved overall survival in a variety of malignancies, there has not been a clinically important impact in CCA. This report presents a 66-year-old patient with chemotherapy-refractory iCCA who experienced a prolonged response to immunotherapy. Tumor genome profiling revealed a high tumor mutation burden of 17 mutations per megabase in the absence of microsatellite instability. He was started on immunotherapy with nivolumab and has experienced an ongoing response for 16 months without clinical symptoms and only minimal radiologic disease.

Topics: Aged; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Capecitabine; Chemoradiotherapy, Adjuvant; Cholangiocarcinoma; DNA Mutational Analysis; Drug Resistance, Neoplasm; Fluorouracil; Humans; Inguinal Canal; Leucovorin; Liver; Liver Neoplasms; Lymphatic Metastasis; Male; Microsatellite Instability; Neoplasm, Residual; Nivolumab; Organoplatinum Compounds; Positron Emission Tomography Computed Tomography; Programmed Cell Death 1 Receptor; Treatment Outcome

Bevacizumab (bev), when added to a moderate dose combination of previously failed cytotoxins, as a third- and fourth-line therapy for refractory gastric, cholangiocarcinoma, and ovarian cancers, produced high-quality responses. The regimen was based on preclinical models designed in order to simultaneously partner both bev and each of the cytotoxins with 4-5 synergistic drugs.. Induction treatment was free of life-threatening complications. Nine consecutive patients, 3 under second- and 6 under multi-line treatment, had 9 objective responses and 8 produced long clinical benefits, 2 of which were complete responses. Seven responses created opportunities for personalized added treatment and research. Absolute median survival was 21.5 months for the 8 patients with platinum-resistant tumors. One patient was unable to tolerate a first standard adjuvant dose of paclitaxel. After rapid peritoneal progression of disease, treatment has produced 52+ months of unmaintained complete remission.. Bev, in the combination that was used in this study, meets response, survival, and toxicity criteria for further testing against second- or multi-line chemotherapy-resistant tumors and also when a standard treatment is not safe.

Topics: Adenocarcinoma; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bile Duct Neoplasms; Camptothecin; Cholangiocarcinoma; Cisplatin; Deoxycytidine; Docetaxel; Endometrial Neoplasms; Female; Fluorouracil; Gemcitabine; Humans; Induction Chemotherapy; Irinotecan; Leucovorin; Middle Aged; Ovarian Neoplasms; Retrospective Studies; Taxoids

To evaluate the efficacy and tolerance of FOLFIRI plus bevacizumab treatment outcome as second-line treatment for metastatic intrahepatic cholangiocarcinoma.. Thirteen consecutive patients with metastatic intrahepatic cholangiocarcinoma who were refractory to first-line therapy consisting of gemcitabine plus oxaliplatin-based first-line chemotherapy given intravenously via intra-arterial infusion were treated with FOLFIRI [irinotecan (180 mg/m² i.v. over 90 min) concurrently with folinic acid (400 mg/m² i.v. over 120 min) followed by fluorouracil (400 mg/m² i.v. bolus) then fluorouracil 2400 mg/m² intravenous infusion over 46 h] and bevacizumab (5 mg/kg) every 2 wk. Tumor response was evaluated by computed tomography scan every 4 cycles.. The best tumor responses using response evaluation criteria in solid tumor criteria were: complete response for 1 patient, partial response for 4 patients, and stable disease for 6 patients after 6 mo of follow-up. The response rate was 38.4% (95%CI: 12.5-89) and the disease control rate was 84.5% (95%CI: 42-100). Seven deaths occurred at the time of analysis, progression free survival was 8 mo (95%CI: 7-16), and median overall survival was 20 mo (95%CI: 8-48). No grade 4 toxic events were observed. Four grade 3 hematological toxicities and one grade 3 digestive toxicity occurred. An adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity, and a delay in chemotherapy cycles was required for 3 patients.. FOLFIRI plus bevacizumab combination treatment showed promising efficacy and safety as second-line treatment for metastatic intrahepatic cholangiocarcinoma after failure of the first-line treatment of gemcitabine plus oxaliplatin chemotherapy.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Camptothecin; Cholangiocarcinoma; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Fluorouracil; France; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Retrospective Studies; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

We report a case of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) that developed in a patient with cholangiocarcinoma after receiving oxaliplatin-based chemotherapy. A 62-year-old man had multiple hypodense lesions with delayed enhancement in the both lobes of the liver on abdominal computed tomography. He was treated with 5-fluorouracil, leucovorin and oxaliplatin (100 mg/m(2)). After eight cycles of treatment and a cumulative oxaliplatin dose of 780 mg/m(2), he developed an unsteady gait, dysphagia, weakness of both the upper and lower limbs and impairment of all sensory modalities. Nerve conduction studies confirmed the diagnosis of AIDP. Immunoglobulin G i.v. was administered for 5 days but the neurological deficits of both his upper and lower limbs did not improve. This case highlights unusual peripheral nervous system manifestations in a patient who received chemotherapy with oxaliplatin.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cholangiocarcinoma; Fluorouracil; Guillain-Barre Syndrome; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin

The prognosis for patients with unresectable intrahepatic cholangiocarcinoma(ICC) is extremely poor. Case 1 was a 65- year-old woman who had an ICC of 9 cm in diameter (mass-forming type) in the right lobe with portal trunk invasion. She was treated with hepatic arterial infusion chemotherapy[cisplatin(CDDP)/5-fluorouracil(5-FU)/l-leucovorin(l-LV)] and radiation therapy (total dose, 50 Gy). After 6 months, abdominal computed tomography (CT) revealed that the tumor had regressed. She survived for 7 years without recurrence of the ICC; subsequently, she died of peritoneal cancer. Case 2 was a 59-year-old woman who had an ICC of 8 cm in diameter (mass-forming type) in the left lobe with lymph node metastasis in the hepatoduodenal ligament; the right hepatic artery was involved by the metastatic lymph nodes. She was treated with hepatic arterial infusion chemotherapy(CDDP/5-FU/l-LV) and radiation therapy(total dose, 30 Gy). After 10 months, abdominal CT revealed that the tumor had disappeared, but paraaortic and mediastinal lymph node metastases were detected. She was therefore treated with systemic chemotherapy. Treatment with systematic chemotherapy enabled her to survive for over 5 years with a good performance status.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Chemoradiotherapy; Cholangiocarcinoma; Cisplatin; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Middle Aged; Neoplasm Staging; Time Factors

Differential diagnosis of liver lesion in the absence of proven primary tumor is still a challenge. We experienced a case of an asymptomatic 14 cm lesion of right hemiliver in a 67 year-old man submitted to right hepatectomy in December 2010. One year before the patient underwent to endoscopic removal of a tubular adenoma of the right colon. Preoperative diagnosis was supported by ultrasound, CT scan, PET and liver biopsy. The patient received 6 cycles of preoperative chemotherapy (FOLFOX) with down-staging of the lesion diameter. Immunohistochemistry on the surgical specimen showed positivity for cytokeratins 19 and 20, CEA, MUC-2, negativity for cytokeratin 7 and a-fetoprotein. Moreover, the neoplastic cells showed a focal positivity with lower intensity for MUC-1 and MUC-5AC. The immunohistochemical profile suggested the possibility of a metastatic tumour from the large bowel, without excluding a primitive mucinous cholangiocarcinoma with intestinal phenotype. At 6 months after intervention, the patient was submitted to chemotherapy (FOLFOX). At present he is in good condition, without radiological signs of recurrence. Oncologists must evaluate the possible benefits of further adjuvant treatments based on the differential diagnosis between a primitive or metastatic liver tumour. In conclusion, correct diagnosis of liver masses is mandatory and remains a challenge that can differentiate either follow-up or surgical and adjuvant treatment. Histology and immunohistochemistry must be related to clinical findings as they may not always be sufficient to reach a correct final diagnosis, and can even be confusing. At present, molecular biology cannot be considered a helpful for diagnosis in these cases.

Topics: Adenoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Cholangiocarcinoma; Diagnosis, Differential; Fluorouracil; Humans; Immunohistochemistry; Intestinal Neoplasms; Leucovorin; Male; Neoplasms, Second Primary; Neoplasms, Unknown Primary; Organoplatinum Compounds

Extrahepatic biliary duct cancers (EBDC) are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT) in a series of patients treated in one institution.. Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma) received 3D conformal external beam RT to a median total dose of 50.4 Gy. Concurrent chemotherapy based on 5-FU was delivered to 21 patients (91%). Surgical margins were negative in 11 patients (48%), narrow in 2 (9%), and microscopically involved in 8 (35%). Eleven patients (55%) had metastatic nodal involvement. The average follow-up time for all patients was 30 months (ranging from 3-98).. Acute gastrointestinal grade 2 toxicity (RTOG scale) was recorded in 2 patients (9%). Nausea or vomiting grade 1 and 2 was observed in 8 (35%) and 2 patients (9%) respectively. Only one patient developed a major late radiation-induced toxicity. The main pattern of recurrence was both loco-regional and distant (liver, peritoneum and/or lung). No difference was observed in loco-regional control according to the tumor location. The 5-year actuarial loco-regional control rate was 48.3% (67% and 30% for patients operated on with negative and positive/narrow/unknown margins respectively, p=0.04). The 5-year actuarial overall survival was of 35.9% for the entire group (61.4% in case of negative margins and 16.7% in case of positive/narrow/unknown margins, p=0.07).. Postoperative RT with 50-60 Gy is feasible with acceptable acute and late toxicities. The potential benefit observed in our series may support the use of adjuvant RT in patients with locally advanced disease. Prospective randomized trials are warranted to confirm definitively the role of RT in this tumor location.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Chemotherapy, Adjuvant; Cholangiocarcinoma; Cisplatin; Combined Modality Therapy; Digestive System Surgical Procedures; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Lymphatic Irradiation; Male; Middle Aged; Radiotherapy, Adjuvant; Radiotherapy, Conformal; Retrospective Studies

This patient is a male in his 30's. He was diagnosed as hepatitis B virus-related huge primary liver cancer, 10cm in diameter, located in segment 4, accompanied with left portal thrombus and multiple lung metastases. Ten months after repeating systemic chemotherapy using gemcitabine (GEM)+carboplatin (CBDCA)+5-FU/leucovorin (LV) and hepatic arterial infusion chemotherapy with cisplatin (CDDP) 4 times, extended left lobectomy with caudate lobe could be successfully performed because of marked reducion of the huge tumor. The pathology revealed almost entirely necrotic changes of the main tumor, and the remaining, viable tumor nests showed combined hepatocellular and cholangiocarcinoma. Systemic chemotherapy was repeatedly given afterwards, which kept the pulmonary metastases stable without growth. The present case suggests that systemic chemotherapy using GEM+CBDCA+5-FU/LV may be useful in the multimodal treatment for the combined hepatocellular and cholangiocarcinoma with distant metastases.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carboplatin; Carcinoma, Hepatocellular; Cholangiocarcinoma; Cisplatin; Combined Modality Therapy; Deoxycytidine; Fluorouracil; Gemcitabine; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male

Cetuximab has been proved to be effective alone or in combination with other chemotherapeutic agents in the treatment of various malignancies. The aim of this report was to describe our experience of using cetuximab with chemotherapeutics agents to treat advanced-stage biliary tract cancer.. We retrospectively analyzed the outcomes of 5 biliary tract cancer patients receiving cetuximab-containing therapy. Four of them had stage IV disease, and 1 patient had incomplete resection at the time of diagnosis. Epidermal growth factor receptor (EGFR) expression and K-ras status were assessed when a specimen was available. After cetuximab treatment, complete response was achieved in 1 patient, partial response in 3 patients, and stable disease in 1 patient. Three surgical specimens were available, and all revealed positive EGFR expression. Only 1 surgical specimen was adequate for K-ras mutation test, and the wild type was confirmed. Complete response was found in the patient who had wild type K-ras. The progression-free survival of these patients varied from 4 to 16 months.. Cetuximab-containing therapy might be an effective treatment for advanced biliary tract cancer.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Camptothecin; Cetuximab; Cholangiocarcinoma; Combined Modality Therapy; Deoxycytidine; Disease Progression; Drug Administration Schedule; Female; Fluorouracil; Gallbladder Neoplasms; Gemcitabine; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Staging; Survival Rate

Confusion still exists in the diagnosis of drug-induced immune haemolysis (DIH). The aim of this study was to demonstrate antibodies specific to 5-fluorouracil (5-FU) in a patient with fatal immune haemolysis (IH). The case of a patient who died due to protracted IH is described. A 57-year-old female underwent treatment with oxaliplatin, 5-FU and folinic acid due to cholangiocarcinoma. Following drug administration, she was transfused because of a mild non-haemolytic anaemia and died following haemolysis. Serological testing including antibody screening, direct antiglobulin test and detection of drug-dependent antibodies was performed using standard techniques. The patient's serum was observed to be red in colour due to the presence of free haemoglobin prior to and following blood transfusion, and contained antibodies reactive with RBCs only in the presence of urine from several patients treated with 5-FU (ex vivo antigens). Drug-induced immune haemolysis (DIH) and metabolite-dependent antibodies should always be taken into consideration when a patient being administered any type of drug develops haemolysis.

Topics: Anemia; Anemia, Hemolytic; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Blood Transfusion; Cholangiocarcinoma; Coombs Test; Cryoglobulins; Dialysis; Drug Hypersensitivity; Fatal Outcome; Female; Fluorouracil; Humans; Leucovorin; Low Back Pain; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Specimen Handling; Temperature

Cholangiocarcinoma is a malignant neoplasm arising from the biliary epithelium. The disease is notoriously difficult to diagnose and is usually fatal because of its late clinical presentation and the lack of effective nonsurgical therapeutic modalities. The overall survival rate, including in patients who underwent tumor resections, is poor, with less than 5% surviving more than 5 years. Over the past 5 years, several important studies have yielded new insight into the molecular mechanisms involved in the development and growth of these tumors. The tumor cells of the cholangiocarcinoma express an epidermal growth factor receptor which plays an important role in the pathogenesis of these tumors.. A 49-year-old woman with cholangiocarcinoma of the liver developed spinal metastases. The antiepidermal growth factor receptor (anti-EGFR) antibody was used successfully in combination with radiotherapy. The response to treatment was assessed by magnetic resonance imaging and positron-emission tomography.. The patient with cholangiocarcinoma had a response to cetuximab-based therapies. This may lead to another option for the treatment of hepatic cholangiocarcinoma.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Bone Neoplasms; Cetuximab; Chemotherapy, Adjuvant; Cholangiocarcinoma; Combined Modality Therapy; ErbB Receptors; Female; Fluorouracil; Humans; Leucovorin; Liver Transplantation; Magnetic Resonance Imaging; Middle Aged; Positron-Emission Tomography; Radiotherapy, Adjuvant; Spinal Neoplasms; Thoracic Vertebrae

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cholangiocarcinoma; Cisplatin; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Time Factors; Treatment Outcome

The patient was a 50-year-old woman who suffered from gastric discomfort. She was first diagnosed as intrahepatic cholangiocarcinoma with hepatic, paraaortic lymphnodal and bone metastasis. Initial systemic chemotherapy using gemcitabine (GEM) and 5-FU failed to control the disease activity. Then she was given GEM and cisplatin (CDDP) combination chemotherapy. The response was assessed as stable disease (SD), but grade 4 leukopenia was seen. Then systemic therapy using GEM, and hepatic arterial infusion therapy with CDDP, l-leucovorin and 5-FU were continued biweekly. Partial response (PR) was achieved six months later, and her disease status was maintained as SD. This hepatic arterial infusion chemotherapy would be safe and feasible as therapy for inoperable intrahepatic cholangiocarcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Bone Neoplasms; Cholangiocarcinoma; Cisplatin; Deoxycytidine; Drug Administration Schedule; Female; Fluorouracil; Gemcitabine; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Middle Aged