Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcinoma: a GERCOR study. Mitomycin C in combination with capecitabine or biweekly high-dose gemcitabine in patients with advanced biliary tract cancer: a randomised phase II trial. Phase II study of systemic gemcitabine chemotherapy for advanced unresectable hepatobiliary carcinomas. Outpatient Therapy with Gemcitabine and Docetaxel for Gallbladder, Biliary, and Cholangio-Carcinomas A Phase II study of gemcitabine and cisplatin in chemotherapy-naive, unresectable gall bladder cancer Weekly Gemcitabine for the Treatment of Biliary Tract and Gallbladder Cancer A phase II study of gemcitabine in gallbladder carcinoma. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. Gemcitabine, 5‐fluorouracil, and leucovorin in advanced biliary tract and gallbladder carcinoma
BACKGROUND Since gemcitabine-oxaliplatin ( GEMOX ) has been used in pancreatic adenocarcinoma , we studied its activity and tolerability in advanced biliary tract adenocarcinoma ( ABTA ) . PATIENTS AND METHODS Consecutive adult patients with confirmed ABTA were recruited from four centers . Those in group A had performance status ( PS ) 0 - 2 , bilirubin < 2.5x normal and received GEMOX as first-line chemotherapy . Those in group B had PS > 2 and /or bilirubin > 2.5x normal and /or prior chemotherapy . All received gemcitabine 1000 mg/m2 as a 10 mg/m2/min infusion on day 1 , followed by oxaliplatin 100 mg/m2 as a 2-h infusion on day 2 , every 2 weeks . RESULTS Tumor sites were gallbladder ( 19 ) , extrahepatic bile ducts ( 5 ) , ampulla of vater ( 3 ) and intrahepatic bile ducts ( 29 ) . Results for group A ( n = 3 ) were : objective response 36 % [ 95 % confidence interval ( CI ) 18.7 % to 52.3 % ] , stable disease 26 % , progressive disease 39 % , median progression-free survival ( PFS ) 5.7 months and overall survival ( OS ) 15.4 months . Results for group B ( n = 23 ) were : objective response 22 % ( 95 % CI 6.5 % to 37.4 % ) , stable disease 30 % , progressive disease 48 % , PFS 3.9 months and OS 7.6 months . National Cancer Institute Common Toxicity Criteria grade 3 - 4 toxicities were neutropenia 14 % of patients , thrombocytopenia 9 % , nausea/vomiting 5 % and peripheral neuropathy 7 % . CONCLUSION The GEMOX combination is active and well tolerated in ABTA BACKGROUND Patients with advanced biliary tract carcinoma face a particularly dismal prognosis , and no st and ard palliative chemotherapy has yet been defined . Among several different single agents , mitomycin C and , more recently , the oral fluoropyrimidine capecitabine and the nucleoside analogue gemcitabine , have been reported to exert antitumour activity . In view of a potential drug synergy , the present r and omised phase II trial was initiated . The aim was to investigate the therapeutic efficacy and tolerance of mitomycin C ( MMC ) in combination with gemcitabine ( GEM ) or capecitabine ( CAPE ) in previously untreated patients with advanced biliary tract cancer . PATIENTS AND METHODS A total of 51 patients were entered in this study and r and omly allocated to treatment with MMC 8 mg/m2 on day 1 in combination with GEM 2000 mg/m2 on days 1 and 15 every 4 weeks , or MMC 8 mg/m2 on day 1 plus CAPE 2000 mg/m2/day on days 1 - 14 , every 4 weeks . In both arms , chemotherapy was administered for a total of 6 months unless progressive disease occurred earlier . RESULTS Pretreatment characteristics were well balanced between the two treatment arms . The overall independent review committee-confirmed response rate among those treated with MMC + GEM was 20 % ( five of 25 ) compared with 31 % ( eight of 26 ) among those treated with MMC + CAPE . Similarly , median progression-free survival ( PFS ; 4.2 versus 5.3 months ) and median overall survival ( OS ; 6.7 versus 9.25 months ) tended to be superior in the latter combination arm . Chemotherapy was fairly well tolerated in both arms , with a comparably low rate of only grade 1 and 2 non-haematological adverse reactions . Also , only four ( 17 % ) patients in both treatment arms experienced grade 3 leukocytopenia , and three ( 13 % ) and four ( 17 % ) had grade 3 thrombocytopenia in the MMC + GEM and MMC + CAPE arm , respectively . CONCLUSIONS The results of this study indicate that both combination regimens are feasible , tolerable and clinical ly active . The MMC + CAPE arm , however , seems to be superior in terms of response rate , PFS and OS , and should therefore be selected for further clinical investigation in advanced biliary tract cancer BACKGROUND / AIMS Patients with advanced unresectable hepatobiliary carcinomas have a dismal prognosis . The efficacy of systemic chemotherapy in these patients is negligible and often , in particular in patients with hepatocellular carcinomas , the toxicity of chemotherapy outweighs the potential palliative effect of antineoplastic agents . Gemcitabine is a new anticancer agent with a mild toxicity profile , which has demonstrated antineoplastic activity in many solid tumors . Therefore we investigated the effect of gemcitabine in patients with advanced nonresectable hepatocellular and cholangiocellular carcinomas in a phase II study . METHODOLOGY Twenty-three patients with cholangiocellular carcinoma and 20 patients with hepatocellular carcinoma were enrolled into the study . Eighteen of the 20 patients with hepatocellular carcinomas had liver cirrhosis .  Gemcitabine was administered once weekly over 30 min for 3 consecutive weeks out of every 4 weeks . Patients with cholangiocellular carcinomas received gemcitabine also in the forth week of the first cycle with no rest to the following cycle . Disease status was assessed every 4 weeks . RESULTS Overall the regimen was well tolerated . The median number of gemcitabine administration was 15 ( range , 3 - 37 ) in the group of patients with cholangiocellular carcinomas and 7.6 ( range , 3 - 21 ) in the group of patients with hepatocellular carcinomas . In the group of patients with hepatocellular carcinomas thrombocytopenia was the most frequent side effect ( 30 % grade 3/4 ) . Among the patients with cholangiocellular carcinomas nausea and neutropenia were the most commonly observed side effects . The overall response rate of hepatocellular carcinomas was only 5 % and chemotherapy generally did not improve the tumor symptoms of the patients in this group . In contrast , in the group of cholangiocellular carcinomas , seven patients achieved a partial response ( overall response rate 30 % ) . Eleven patients with cholangiocellular carcinomas revealed tumor symptoms before the onset of gemcitabine treatment . Seven of these patients developed a treatment related clinical benefit as defined as a relief of tumor symptoms or gain of weight . CONCLUSIONS Our results indicate that the treatment of cholangiocarcinomas with gemcitabine is effective and should be further evaluated in phase III studies . In contrast , palliative chemotherapy with gemcitabine can not be recommended in patients with hepatocellular carcinoma and liver cirrhosis Abstract Purpose . The prognosis of patients withbiliary tree carcinomas is very poor . Thediagnosis often occurs at an advancedstage , when curative resection is notpossible . We combined gemcitabine and docetaxel to optimize the palliativetherapy for patients with gallbladder , biliary , and cholangio-carcinomas on anoutpatient basis . Patients and methods . Patients withhistologically proven biliary treecarcinomas and a WHO performance status<2 received gemcitabine 1000 mg/m2followed by docetaxel 35 mg/m2 weekly for 3weeks followed by 1 week of rest . Results . Forty-three patients , 14males/29 females , with an average age of63.3 years ( range , 41 to 78 ) have beenenrolled since 1998 ; 37 have completedtreatment . So far , 168 cycles ( range , 1 to16 ) have been administered . All 43 patients were included in the response and toxicity assessment s. There are no completeremissions ; however , 4 ( 9.3 % ) patients achieved partial remission , 1 ( 2.3 % ) had aminimal remission , and 24 (55.8%)reached disease stabilization for a medianperiod of 5.2 months . Fourteen ( 32.6 % ) patients progressed . The median overallsurvival rate is currently 11.0 months . Grade 3 hematologic toxicities wereinfrequent , and there were no grade 4hematologic toxicities . Grade 3 leukopeniawas reported in 4 ( 9.3 % ) patients , grade 3thrombozytopenia in 1 ( 2.3 % ) patient , and grade 3 anemia in 1 ( 2.3 % ) patient . Twenty-eight ( 65.1 % ) patients had grade 3/4 alopecia , 8 ( 18.6 % ) hadnausea/vomiting , and 2 ( 4.6 % ) hadmucositis . Conclusion . The combination ofgemcitabine/docetaxel is an effective and well tolerated therapy for patients withadvanced or metastatic gallbladder , biliary , and cholangio-carcinomas The primary objective of this study was to determine the response rates of the gemcitabine and cisplatin combination in unresectable gall bladder cancer patients . The secondary objectives were to evaluate the toxicity , time to progressive disease , and overall survival . Chemonaïve patients with histologically proven , unresectable bidimensionally measurable gall bladder cancer were enrolled into this study . All patients were required to have a Zubrod 's performance status ⩽2 , no prior radiotherapy , and adequate major organ function . Patients received gemcitabine ( 1000 mg m−2 intravenously over 30–60 min ) on days 1 and 8 , and cisplatin ( 70 mg m−2 intravenously over 2 h ) on day 1 , every 21 days . Response assessment was done by a CT scan after every other cycle of chemotherapy . In all , 30 patients were eligible for efficacy and toxicity analysis . There were four ( 13.3 % ) complete responders , seven ( 23.3 % ) partial responders , and seven ( 23.3 % ) with stable disease , with four ( 13.2 % ) patients showing disease progression . The median time to progression was 18 weeks ( 95 % confidence interval ( CI ) 14–24 weeks ) , and the median duration of response was 13.5 weeks ( range 5.5–104 weeks ) . The median overall survival was 20 weeks ( 95 % CI 14–31 weeks ) , with 1-year survival rate of 18.6 % . WHO grade 3 or 4 anaemia was seen in seven ( 23.3 % ) and four ( 13.3 % ) patients , respectively . Five ( 16.6 % ) patients each experienced grade 3 or 4 neutropenia , and grade 3 or 4 thrombocytopenia was seen in three ( 10 % ) and two ( 6.6 % ) patients , respectively . The present study shows that gemcitabine/cisplatin combination is well tolerated and active in advanced unresectable gall bladder cancer Objectives : To evaluate the efficacy and safety of weekly administration of gemcitabine treatment in chemotherapy-naïve patients with advanced biliary tract and gallbladder cancer . Patients and methods : Gemcitabine at a dose of 800 mg/m2 was administered weekly as a 30-min infusion to patients with previously operated , histologically confirmed , metastatic , or unresectable locally advanced cholangiocarcinoma . Treatment was continued until unacceptable toxicity or disease progression . Results : A total of 30 patients ( median age 66 years ; range 54–72 years ) were included in the study . A median of 14 ( range , 4–33 ) weekly doses was administered . Out of 30 patients evaluable for response , nine partial responses were observed ( 30.0 % ) , while a further 11 patients demonstrated stable disease ( 36.7 % ) . The median time to disease progression was 7 months ( range , 5–34 ) . Overall response rate was superior in patients with cancer of the gallbladder ( ORR=35.7 % ) compared with those patients with biliary duct cancer ( ORR=27.3 % ) . This correlated to a significantly longer time to progression of 6.4 months ( 95 % confidence interval ( CI ) , 5.6–7.1 months ) versus 3.6 months ( 95 % CI , 2.9–4.3 months ; p=0.03 ) and a significantly better overall survival of 17.1 months ( 95 % CI , 15.8–18.5 months ) versus 11.4 months ( 95 % CI , 10.2–12.6 months , p=0.021 ) . Toxicities were generally mild with only one case of grade 3 neutropenia . There were no cases of febrile neutropenia and no treatment-related deaths . Conclusions : Weekly administration of gemcitabine provides a safe , well-tolerated , and effective treatment for chemotherapy naïve patients with advanced cholangiocarcinoma , particularly with a gallbladder origin BACKGROUND Due to the high mortality rates from gallbladder carcinoma in Chile , we conducted a phase II trial to test the efficacy and safety of gemcitabine in patients with locally advanced or metastatic gallbladder carcinoma . PATIENTS AND METHODS From January 1998 to February 2000 , 26 patients with metastatic or unresectable gallbladder carcinoma and no prior chemotherapy received gemcitabine 1,000 mg/m2 over 30 minutes weekly for three weeks followed by a week of rest . RESULTS Patients received a median of 4.2 cycles ( range 1 - 10 ) . Out of the 25 patients whose response could be evaluated , 9 went into partial remission , an overall response rate of 36 % ( 95 % confidence interval ( 95 % CI ) : 17.1 % to 57.9 % ) . In six ( 25.0 % ) patients , the cancer remained stable , and in 10 ( 40 % ) it progressed . Median survival time was 30 weeks ( range 7 - 80 + . Hematological toxicities were mild , with no cases of febrile neutropenia or hemorrhage . However , four and one patient(s ) had grade s 1 - 2 and 3 - 4 neutropenia , respectively , and two patients had grade 2 thrombocytopenia . Nine patients experienced grade 1 - 2 nausea/vomiting , but were able to continue treatment . There were no toxic deaths . CONCLUSIONS In this phase II trial , gemcitabine is an active chemotherapy in metastatic or inoperable gallbladder carcinoma , with a manageable toxicity profile PURPOSE Biliary cancer has a poor prognosis , and chemotherapy has had little impact . The objectives of this trial were to determine the response rate , time to disease progression , survival , and safety profile of the combination of gemcitabine and capecitabine ( GemCap ) in patients with advanced biliary cancer . PATIENTS AND METHODS Eligible patients had pathologically proven , locally advanced or metastatic adenocarcinoma arising from the intra- and extrahepatic bile ducts or gallbladder with no prior chemotherapy . Patients were treated on a 3-week cycle consisting of capecitabine at 650 mg/m(2 ) orally twice a day for 14 days and gemcitabine at a fixed dose of 1,000 mg/m(2 ) intravenously over 30 minutes on days 1 and 8 . RESULTS Forty-five patients were enrolled between July 2001 and January 2004 . Fifty-three percent of patients had cholangiocarcinoma , 47 % had gallbladder cancer , and 89 % had metastatic disease . The overall objective response rate was 31 % , with an additional 42 % of patients with stable disease , for a disease control rate of 73 % . The median overall survival time was 14 months ( 95 % CI , 7.3 months to not available ) , and the median progression-free survival time was 7 months ( 95 % CI , 4.6 to 11.8 months ) . This chemotherapy combination was generally well tolerated . Transient neutropenia , thrombocytopenia , fatigue , and h and -foot syndrome were commonly observed but were easily managed without discontinuing further treatment . CONCLUSION The significant antitumor activity combined with a mild toxicity profile seen in this study argue that GemCap chemotherapy may benefit patients with advanced biliary cancer . This regimen warrants further evaluation in a r and omized study with survival and quality of life end points 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 )
BACKGROUND Cholangiocarcinoma and gallbladder cancer are difficult to treat curatively .
The treatment of choice is surgery , dependent on detection at a resectable stage .
No chemotherapy or radiotherapy options have shown substantial activity .
Gemcitabine has demonstrated response in similar cancers .
Considering the lack of treatment options for cholangiocarcinoma and gallbladder cancer , a systematic review of the evidence on gemcitabine use for these indications was performed .
OBJECTIVE To perform a systematic review to evaluate the role of gemcitabine in the treatment of cholangiocarcinoma and gallbladder cancer .