Gemcitabine Combination Chemotherapy Research Articles

Efficacy of gemcitabine as second-line therapy after S-1 therapy failure in advanced pancreatic carcinoma.

248 Background: Gemcitabine (GEM) and GEM-containing combination chemotherapy have been established as standard first-line therapies for advanced pancreatic carcinoma (APC). In the GEST study, a phase III clinical trial that compared the results for GEM, S-1, and GEM+S-1 therapies, there was no significant difference between overall survival (OS) for GEM and GEM+S-1; S-1 and GEM had similar efficacies as first-line treatment for APC. Therefore, S-1 is expected to be used as first-line therapy. In our study, we have evaluated the efficacy and outcomes of second-line GEM therapy after S-1 therapy failure in APC. Methods: We retrospectively examined the data for 27 patients (pts) with APC refractory to first-line S-1 therapy. All the pts had undergone second-line GEM therapy during October 2000–February 2009 at National Cancer Center Hospital after first-line S-1 therapy. Tumor responses were analyzed using Response Evaluation Criteria in Solid Tumors. The Kaplan-Meier method was used to evaluate tumor progression and survival. Results: The Eastern Cooperative Oncology Group Performance Status was 0 or 1. The male:female ratio was 16:11 and median age was 62 years (range, 42–75 years). Four pts (14%) exhibited a partial response to second-line GEM therapy, 11 (40%) showed stable disease, and 12 (44%) showed progressive disease. Grade 3 adverse events for second-line GEM therapy were neutropenia in 2 pts and upper gastrointestinal hemorrhage in 1 pt. Grade 4 adverse events were not observed. The median progression-free survival was 77 days (95% confidence interval, 33–121 days) and the median OS after second-line GEM therapy was 240 days (95% confidence interval, 156–324 days). Conclusions: Although this study had a small sample population and retrospective design, the results indicate that GEM has good antitumor activity with tolerable toxicity. Second-line GEM therapy was found to be effective after first-line S-1 therapy failure in APC.

A case of advanced lung cancer treated by surgery followed by adjuvant combination therapy of gefitinib and interleukin-2 lymphokine-activated killer cell immunotherapy

A smoker, 55-year-old male with a small nodule in left S5 on computed tomographic (CT) scanning of chest was diagnosed with pulmonary adenocarcinoma (cT1N0M0, c-stage IA). However, the CT scanning revealed that several small nodules on pleural surface might suspect a pleural dissemination, that is, IV-staged advanced lung cancer. The patient desired for receiving an aggressive multimodality containing of surgery, immunotherapy, and gefitinib treatment. After thoracotomy, the small pleural nodules were intraoperatively diagnosed with pleural dissemination by pathological examination. However, there was no malignant pleural effusion and intraoperative cytological examination of intrathoracic lavage resulted in a negative finding. Because of clinical N2-negative disease without malignant pleural effusion, left upper lobectomy with mediastinal lymph nodes dissection was preceded. The postoperative pathological examination disclosed pulmonary adnocarcinoma with mixed subtypes (pT1N2M1a, p-stage IV) and with micropapillary pattern. A detection test of epidermal growth factor receptor (EGFR) gene mutation revealed a positive result (L858R). As a systemic therapy, a combination chemotherapy of gemcitabine and carboplatin was performed in 2 cycles for the remained pleural dissemination. The patient received combination therapy of gefitinib and interleukin-2 lymphokine-activated killer cell immunotherapy in 6 cycles. A CT scanning of chest displayed disappearances of the remained pleural dissemination. There had been uneventful for 25 months. On the third postoperative year, a stereotactic radiotherapy surgery was performed for small three brain metastases. He had been healthy and received the gefitinib treatment for 45 months without any regrowing of the irradiated cerebral metastases and the treated pleural dissemination. The combination therapy of gefitinib and immunotherapy in the postoperative early phase would take advantage of extending the patient's progression-free survival, and also in case of the selected population of the advanced lung cancer harboring a EGFR mutation-positive.

Reversal of jaundice in two patients with inoperable cholangiocarcinoma treated with Cisplatin and gemcitabine combination.

Two patients are presented with severe jaundice, due to inoperable cholangiocarcinoma. The chemotherapeutic approach in patients with severe jaundice is discussed. Many schedules of chemotherapy were developed in this tumor type with normal serum bilirubin. We report here the first successful use of cisplatin and gemcitabine combination chemotherapy in these patients. Tolerability was good and liver function tests gradually improved.

Gemcitabine and Cisplatin Combination Chemotherapy in Triple Negative Metastatic Breast Cancer Previously Treated with a Taxane/Anthracycline Chemotherapy; Multicenter Experience

This study was aimed to establish clinical efficacy and tolerability of gemcitabine and cisplatin combination in patients with metastatic triple negative breast cancer progressing after anthracycline and taxane based chemotherapies.Thirty-three patients who were given cisplatin and gemcitabine for triple negative and metastatic breast cancer were evaluated retrospectively. A total of 141 cycles were administered with a median 4 cycles per patient. Median follow-up time was 14 months (range, 2-36 months). Objective response rate was 27.3%. Total clinical benefit of the combination was 48.4%. The estimated median progression free survival and median overall survival were 5 months and 14 months, respectively. The most common Grade 3 and 4 toxicity were neutropenia and thrombocytopenia observed in 10 (27.7%) and 9 (24.9%) patients, respectively. The combination of the gemcitabine and cisplatin after taxane/anthracycline is well tolerated and seems to be effective with acceptable toxicity profile.

Gemcitabine and cisplatin-based combination chemotherapy in advanced hepatocellular carcinoma: An Indian experience

Background:Gemcitabine, an anti-metabolite, has some activity in hepatocellular carcinoma (HCC) in terms of responses and median survival.Aims:To analyze our experience with the use of gemcitabine in combination with cisplatin in HCC with respect to response, toxicity and survival.Materials and Methods:We studied the records of patients of HCC treated from January 2000 to December 2005 with gemcitabine and cisplatin, and found 24 of them to be evaluable for response, toxicity and survival.Results:Of 24 patients receiving three or more cycles of chemotherapy, six (25%) had a partial response and an additional 12 (50%) had stable disease. The median overall survival (OS) was 7.5 months (95% confidence interval, 4.5–10.5 months) and 1-year survival was 18%. Grade 3 and 4 anemia, thrombocytopenia and neutropenia were observed in, respectively, 17, 17 and 33% patients. The most frequent non-hematologic toxicities were nausea and vomiting and peripheral neuropathy.Conclusion:We report a partial response rate of 25% with stable disease in an additional 50% to three or more cycles of chemotherapy with gemcitabine and cisplatin, with a median OS of 7.5 months (95% confidence interval, 4.5–10.5) and acceptable toxicity profile from our single-center retrospective study of 24 patients of HCC. We trust that, in HCC, gemcitabine is a good drug to be the foundation to build the chemotherapeutic or targeted agents’ combinations on.

Phase II Trial of Biweekly Paclitaxel and Gemcitabine as Second-Line Chemotherapy for Non-Small Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy

A phase II study was conducted to evaluate the feasibility and efficacy of biweekly administration of paclitaxel and gemcitabine in patients with non-small cell lung cancer (NSCLC) who had been treated previously with platinum-based chemotherapy.Paclitaxel (150 mg/m )and gemcitabine (1,000 mg/m )were administered biweekly for at least 4 cycles.Thirty-one patients with a median age of 64 years (39-75 years) were enrolled in this study(stage IIIB/IV:11/20,PS 0/1/2:13/16/2).Partial response was observed in 7 cases (23%),and stable disease was seen in 18 cases (58%).Median survival time was 8.8 months with a one-year survival rate of 41.9 %.Hematological toxicities were mild and neutropenia of grade 3 or above was observed in one patient (3%).Non-hematological toxicities were also mild, including neurotoxicity (3%). Biweekly paclitaxel and gemcitabine combination chemotherapy was effective and tolerated well as second-line therapy against NSCLC.Shinshu Med J 59 : 411―418, 2011 (Received for publication May 2,2011;accepted in revised form August 8,2011)

Phase II study of a cremophor-free, polymeric micelle formulation of paclitaxel for patients with advanced urothelial cancer previously treated with gemcitabine and platinum

Genexol-PM is a novel Cremophor® EL (CrEL)-free polymeric micelle formulation of paclitaxel. This multicenter phase II study was designed to evaluate the efficacy and safety of Genexol-PM monotherapy in patients with advanced urothelial carcinoma who developed disease progression after gemcitabine and cisplatin combination chemotherapy. Patients received Genexol-PM 240 mg/m(2) intravenously over 3 h every 3 weeks without premedication. Intra-patient dose escalation to 300 mg/m(2) was allowed during the second and subsequent cycles if pre-specified toxicities were not observed during the first cycle. The primary endpoint was response. Thirty-seven patients were enrolled in this study. Platinum-free interval was less than 6 months in 27 (73%) patients, and 24 (64%) were categorized as having intermediate or poor prognosis according to Bajorin's criteria. Of 34 evaluable patients, there were 7 responses (21%; 95% CI, 7-34%), including one complete response (CR), with a median response duration of 6.5 months (95% CI, 3.5-9.6 months). The median time to progression was 2.7 months (95% CI, 0.9-4.6 months) with a median overall survival of 6.5 months (95% CI, 5.0-8.0 months). The most common grade 3/4 non-hematologic toxicities were peripheral neuropathy (sensory type 5.9%; motor type 8.8%) and infection (5.9%). Grade ≥3 hematologic toxicities occurred in only one patient. Genexol-PM was generally well tolerated and demonstrated sufficient antitumor activity to warrant further development when used as second-line chemotherapy after gemcitabine-cisplatin failure in patients with urothelial carcinoma (NCT01426126).

The clinical observation on the effect of gemcitabine plus oxaliplatin in treatment of relapsed or refractory non-Hodgkin's lymphoma

Objective To analyze the clinical efficacy of gemcitabine plus oxaliplatin in treatment of relapsed or refractory non-Hodgkin's lymphoma(NHL).Methods 39 cases with relapsed or refractory NHL were treated by gemcitabine and oxaliplatin combination chemotherapy. After three cycles, its efficacy and adverse reactions were observed. Serum lactate dehydrogenase(LDH) concentration was detected before and after treatment and all the patients were followed up. Results The rate CR was 11cases (28. 1％ ), PR 16cases (41.03％), NC 7cases (17.95％),PD 5cases(12.82％).Thetotalresponserate(CR+PR) was 69. 23％. Conclusion Gemcitabineand oxaliplatin combination chemotherapy in treatment of patients with relapsed or refractory NHL was safe and effective. Key words: Lymphoma, non-hodgkin's; Gemcitabine; Oxaliplatin

Gemcitabine and Oxaliplatin Combination Chemotherapy for Patients with Refractory Pancreatic Cancer

Objective: The aim of this study was to investigate the effect of gemcitabine and oxaliplatin combination chemotherapy on refractory pancreatic cancer. Methods: Patients with advanced pancreatic cancer refractory to gemcitabine and S-1 were treated with gemcitabine 1,000 mg/m² over 30 min and oxaliplatin 85 mg/m² over 120 min on days 1 and 15. Treatment was repeated every 4 weeks and tumor response was assessed every two cycles by RECIST version 1.0. Results: Twenty-two patients with pathologically confirmed pancreatic cancer were enrolled. The treatment was administered as a second-line chemotherapy in eighteen patients (82%) and as a third-line chemotherapy in four patients (18%). Tumor response did not occur in any of the cases. Thirteen patients demonstrated stable diseases, and the disease control rate was 59%. Median overall survival and time to progression were 6.8 months (95% CI, 2.8–11.5) and 2.6 months (95% CI, 1.5–3.8), respectively. Median overall survival from the first-line chemotherapy was 22.7 months (95% CI, 14.8–24.4). The major grade 3/4 adverse events included neutropenia (14%), anorexia (23%), and peripheral neuropathy (14%). Conclusions: Gemcitabine and oxaliplatin combination chemotherapy was tolerable but had limited activity in patients with advanced pancreatic cancer in a refractory setting.

Reversible Posterior Leukoencephalopathy Syndrome Associated with Concurrent Bevacizumab, Gemcitabine, and Oxaliplatin for Cholangiocarcinoma

Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare disorder characterized by altered mental status, seizure, hypertension, and symmetrical white matter edema (leukoencephalopathy) typically in the posterior cerebral hemispheres on brain imaging. It is often linked to certain medication use, in particular, chemotherapeutic agents. Here, we present a case of chemotherapy-related RPLS and review the current literature on this topic. We report a case of RPLS associated with concurrent bevacizumab (Avastin), gemcitabine, and oxaliplatin use for unresectable intrahepatic cholangiocarcinoma. This is the first reported case of RPLS associated with bevacizumab, gemcitabine, and oxaliplatin combination chemotherapy. Concurrent use of multiple agents could significantly increase the risk of RPLS, a potentially fatal disease. Our case suggests that gradual progression of hypertension and proteinuria may be early warning signs before the onset of RPLS that should alarm clinicians.

Combination chemotherapy of gemcitabine and cisplatin by double way plus implantation of radioactive seed 125I in treating stage III non-small cell lung cancer

Objective To assess the therapeutic effect of combination chemotherapy of gemcitabine and cisplatin by double way plus implantation of radioactive seed 125I implantation in treating stage Ⅲ non-small cell lung cancer. Methods Sixty cases with stage Ⅲ non-small cell lung cancer were randomly divided into two groups with random number table. In group A (in interventional treatment group, n = 30),the gemcitabine 1000 mg/m2 and one third of the cisplatin 100 mg/m2 was given using seldinger technique for transcatheter bronchial arterial infusion chemotherapy on day 1. Two-thirds of the cisplatin 100 mg/m2 was infused in veins on day 2 and 3. The gemcitabine 1000 mg/m2 was infused in veins on day 8, 21 days for a period. In group B (interventional - 125I groups), the method of combination chemotherapy of gemcitabine and cisplatin was the same as in Group A. After ten days of arterial perfusion, 125I seeds were implantated, 21 days for a period. All patients received at least 2 cycles. The imaging evaluation of patients after treatment standards included complete remission (CR), partial remission (PR), stable (SD),progressive disease (PD), effective rate (CR + PR)/30 and clinical benefit rate (CR + PR + SD)/30.Non-parametric rank sum test was used to compare short-term effect of the two groups treatment of two cycles.x2 test was used to compare year survival, Kaplan-Meier method was used to calculate median survival,log-rank test method was used to difference between the groups. Results In group A, there were 17 PR,9SD and 4 PD. The overall response rate was 56. 7% (17/30) and clinical beneficial rate was 86. 7% (26/30). In Group B, there were 2 CR, 21 PR, 7 SD. The overall response rate was 76.7% (23/30) and clinical beneficial rate was 100% (30/30). There was significant difference between the two groups (P =0. 036). In group A, the 1 year survival rate was 46. 7% (14/30) and the 2 year survival rate was 36. 7%(11/30), median survival time (MST) was 10 months . In group B, the 1 year survival rate was 76. 7%(23/30) and the 2 year survival rate was 63. 3% (19/30) , median survival time (MST) was 27 months.There was a significant difference between two group in 1 year survival rate (P = 0. 017), 2 year survival rate (P = 0. 039) and median survival time (P = 0. 006). Conclusion The treatment effects of Ⅲ stage non-small cell lung cancer by gemcitabine and cisplatin combination chemotherapy with double way plus radioactive seed 125I implantation was better than gemcitabine and cisplatin combination chemotherapy with double way. Key words: Carcinoma,non-small-cell lung; Radiology,interventional; Iodine isotopes

Phase II study of a polyethoxylated castor oil–free, polymeric micelle formulation of paclitaxel for patients with advanced urothelial cancer previously treated with gemcitabine and platinum.

272 Background: Paclitaxel-loaded polymeric micelle (Genexol-PM; G-PM) is a novel polyethoxylated castor oil (Cremophor EL [CrEL])-free formulation of paclitaxel. This multicenter phase II study was designed to evaluate the efficacy and safety of the G-PM monotherapy for the treatment of gemcitabine- and cisplatin-refractory advanced urothelial cancer. Methods: Patients with advanced urothelial cancer received G-PM 240 mg/m2 intravenously over 3 hours every 3 weeks without premedication as salvage chemotherapy after failure to gemcitabine and cisplatin combination chemotherapy. Intrapatient dose escalation of G-PM to 300 mg/m2 was carried out from the second cycle if the prespecified toxicities were not observed after the first cycle. Results: Thirty-seven patients were enrolled in this study. Platinum-free interval was less than 6 months in 72% of patients and 64% of patients were categorized into intermediate or poor prognostic group. Overall response rate was 19% including one complete response. When response occurs it is long lasting with a median response duration of 7.8 months (range 1.5∼19.3+). The median progression-free survival was 2.7 months (95% CI, 09-4.6) with a median overall survival of 5.7 months (95% CI, 3.1-8.3). The most common major grade 3-4 non-hematologic toxicity was peripheral neuropathy (sensory type 5.6% and motor type 8.3%) followed by infection (5.6%). Grade 3 or worse hematologic toxicities were observed in only one patient. Conclusions: G-PM showed modest activity with favorable toxicity profiles when used as salvage therapy after gemcitabine-cisplatin failure in advanced urothelial cancer. No significant financial relationships to disclose.

Phase II study of fixed-dose-rate infusion of gemcitabine and UFT combination chemotherapy in patients with advanced bile duct cancer: Daegu Gyeoungbuk Oncology Group.

280 Background: This phase II study evaluated efficacy of fixed dose rate (FDR) infusion of gemcitabine (10mg/m2/min) and UFT combination in chemo-naïve patients with advanced bile duct cancer. Methods: This was an open-label, single-arm, multicenter, phase II study with a Simon two-stage minimax design. Patients received the FDR gemcitabine 1,000mg/m2 for 3 consecutive weeks and UFT 400 mg/m2 on days 1-21. The cycle was repeated every 28 days. The primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) -defined objective response rate. Secondary end points included clinical benefit response (CBR), safety, progression-free survival (PFS), and overall survival (OS). Clinical characteristics including four single nucleotide polymorphisms in DNA repair genes (RecQ1, RAD54L, XRCC1, ATM) were evaluated whether these influence the overall survival. Results: Between December 2006 and February 2008, fifty-one patients were enrolled, with a median age of 58 years. The majority of patients (76%) had intra-hepatic disease. Fourteen patients (27%) had a RECIST investigator-assessed, partial response (PR); disease control rate (PR + stable disease) was 55%. CBR was 14% among 37 evaluable patients. Hematologic toxicity was main grade 3 or 4 treatment-related adverse events. Median PFS was 4.0 months (95% CI, 2.9 to 5.1 months). Median OS was 7.0 months (95% CI, 3.5 to 10.5 months). Intrahepatic disease, poor performance, and, XRCC1 R194W C/C type were predictive markers of poor overall survival. Conclusions: FDR gemcitabine and UFT demonstrated apparent activity in patients with advanced bile duct cancer. However, this activity did not translate to prolong survival. The location of disease, performance status, and, polymorphic variants of DNA repair genes may affect clinical outcome of patients with advanced bile duct cancer. No significant financial relationships to disclose.

Increased Expression of P-Glycoprotein Is Associated with Doxorubicin Chemoresistance in the Metastatic 4T1 Breast Cancer Model

Development of drug resistance is one of the major causes of breast cancer treatment failure. The goal of this study was to understand the chemoresistance mechanism using the highly metastatic 4T1 breast cancer model, which emulates stage IV breast cancer in humans. The metastatic 4T1 breast cancer cell line treated with either doxorubicin or 5-FU showed a concentration-dependent reduced cell proliferation, with induced G2-phase growth arrest (doxorubicin) or G1-phase growth arrest (5-FU). Doxorubicin treatment partially suppressed the multiorgan metastasis of 4T1 breast cancer cells in the lung, heart, liver, and bone, compared with either 5-FU or cyclophosphamide. We isolated and characterized 4T1 breast cancer cells from doxorubicin-resistant metastatic tumors (cell line 4T1-R). Multiorgan metastasis of drug-resistant 4T1 breast tumors was totally resistant to doxorubicin treatment. Our results indicate that doxorubicin is localized exclusively in the cytoplasm of resistant 4T1 breast cancer cells and that it cannot reach the nucleus because of increased nuclear expression of P-glycoprotein. Pretreatment of doxorubicin-resistant 4T1-R breast cancer cells with verapamil, a general inhibitor of P-glycoprotein, increased nuclear translocation of doxorubicin and cellular cytotoxicity. Thus, impaired nuclear translocation of doxorubicin due to increased expression of P-glycoprotein is associated with doxorubicin resistance of highly metastatic 4T1 breast cancer.

Recent progress and limitations of chemotherapy for pancreatic and biliary tract cancers

Gemcitabine chemotherapy has been the standard for advanced pancreatic cancer for more than a decade. New oral fluoropyrimidines such as S-1 and capecitabine are other key drugs. Gemcitabine plus erlotinib was the only combination therapy that significantly prolonged survival, although the effect was minimal. Little or no improvement in survival with recent molecular-targeted drugs might be attributed to the very high incidence of K-ras gene mutation in pancreatic cancer. Recently, the non-gemcitabine-based-regimen of FOLFIRINOX showed significantly greater overall survival compared with gemcitabine for the first time. For biliary tract cancer, gemcitabine plus cisplatin combination chemotherapy has been proved to significantly prolong survival and will become the standard therapy. Further improvement in survival is expected by the addition of cetuximab.

A Pilot Study of Gemcitabine and Epirubicin Combination Chemotherapy as a Salvage Regimen for Recurrent Platinum Resistant and/or Refractory Epithelial Ovarian Cancer

BACKGROUND AND OBJECTIVES: The objective of this study was to assess the antitumor activity and toxicity profile of gemcitabine combined with epirubicin in patients with recurrent platinum refractory ovarian epithelial cancer. PATIENTS AND METHODS: Patients with recurrent platinum refractory ovarian cancer and with adequate hematologic, renal and hepatic function and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 were enrolled. The regimen was Gemcitabine 1000 mg/m2 (day 1, 8) and Epirubicin 60 mg/m2 (day 1), the cycle was repeated at interval of 21 days. RESULTS: Twenty eight patients were recruited and received 156 cycles of gemcitabine-epirubicin combination chemotherapy (median 6 cycles). Overall response rate was 42.9% (95% CI equal 24.5 to 62.7) and tumor control rate was 75% (95% CI equal 55.1 to 89.3). No complete responses were observed. Median progression-free and median overall survival times were 7 and 15 months, respectively. The most common grade 3/4 hematological toxicities were neutropenia (57.1%), anemia (10.7%), and thrombocytopenia (7.1%), while the most common grade 3/4 non-hematological toxicities were mucositis (14.3%) and vomiting (3.6%). No treatment related deaths were observed. CONCLUSION: Gemcitabine combined with epirubicin regimen appeared to offer an acceptable clinical profile in patients with recurrent platinum-refractory epithelial ovarian cancer.

Gemcitabine and vinorelbine combination is effective in both as a salvage and mobilization regimen in relapsed or refractory Hodgkin lymphoma prior to ASCT

We investigated the efficacy of gemcitabine and vinorelbine (Gem/Vin) combination chemotherapy as a salvage and mobilization regimen in relapsed or refractory Hodgkin lymphoma (HL) patients prior to autologous hematopoietic stem cell transplantation. We retrospectively reviewed the data of our relapsed or primary refractory HL patients treated with Gem/Vin regimen which consisted of gemcitabine 1,000mg/m(2)/day and vinorelbine 30mg/m(2)/day on days1, 8, and 15 every 28days. The overall response rate was 72.4%. Ten (34.5%) patients achieved complete remission, 11 (37.9%) partial remission, and eight (27.6%) patients had no response. Mobilization with Gem/Vin regimen was successful in 20/23 (87%) patients while mobilization failure was seen in three (13%) patients. Gemcitabine and vinorelbine is an effective salvage regimen with acceptable toxicity and high mobilization potential in relapsed or refractory HL patients.

Combination of gemcitabine and cisplatin is highly active in women with endometrial carcinoma

AbstractBACKGROUND:The treatment of patients with advanced or recurrent endometrial cancer remains problematic, because chemotherapy and hormonal therapy have yielded low response rates and limited progression‐free survival. Because the combination of gemcitabine and cisplatin demonstrated synergism in preclinical studies, the authors attempted to determine the efficacy and toxicity of this combination in women with advanced or recurrent endometrial cancer.METHODS:A prospective, single‐institution, phase 2 study was performed in women with histologically documented International Federation of Gynecology and Obstetrics (FIGO) stage III or IV or recurrent endometrioid endometrial carcinoma. Gemcitabine at a dose of 1000 mg/m2 and cisplatin at a dose of 35 mg/m2 were administered intravenously on Days 1 and 8 of each 21‐day cycle; because of myelosuppression, the protocol was revised to gemcitabine at a dose of 900 mg/m2 and cisplatin at a dose of 30 mg/m2. Patients were treated until disease progression, unacceptable toxicity, or complete response.RESULTS:A total of 21 patients were enrolled and received a median of 5 courses of therapy (range, 1‐9 courses). The median age at the time of study enrollment was 62 years (range, 41‐75 years). Of 20 evaluable patients, 2 (10%) had a confirmed complete response, 8 (40%) had a partial response, 6 (30%) had stable disease, and 4 (20%) developed progressive disease. The median progression‐free survival was 7.5 months (range, 2.3‐33.6 months), and the median overall survival was 18.2 months (range, 2.5‐49.4 months). The development of toxicity mandated dose reductions in 16 of 20 patients (80%). Eighteen patients experienced grade 3 or 4 toxic effects (graded according to the Common Terminology Criteria for Adverse Events [version 3.0]).CONCLUSIONS:The objective response rate of 50% noted with gemcitabine and cisplatin combination chemotherapy merits the further development of this regimen in women with advanced or recurrent endometrial cancer. Cancer 2010. © 2010 American Cancer Society.

Feasibility study of gemcitabine and cisplatin combination chemotherapy for patients with refractory biliary tract cancer

Gemcitabine and cisplatin combination chemotherapy have been shown to have promising efficacy for the treatment of advanced biliary tract cancer (BTC) as a first-line chemotherapy. However, this treatment has not been approved for clinical practice in Japan. Oral fluoropyrimidines (e.g., S-1 and capecitabine) are also promising agents that are widely used with or without gemcitabine. Unfortunately, there is no standard chemotherapy for patients refractory to gemcitabine and oral fluoropyrimidine. We conducted a feasibility study of gemcitabine and cisplatin combination chemotherapy for patients with advanced BTC who are refractory to gemcitabine and S-1. Gemcitabine (1,000mg/m(2)) and cisplatin (25mg/m(2)) were administered intravenously on days 1 and 8, and this regimen was repeated every 3weeks. Tumor response was assessed every two cycles using the Response Evaluation Criteria in Solid Tumors version 1.0. Twenty patients with pathologically confirmed BTC were enrolled. Gemcitabine and cisplatin combination chemotherapy was administered as a second-line chemotherapy in thirteen patients and as a third-line chemotherapy in seven patients. Tumor response did not occur in any of the cases. Fourteen patients demonstrated stable diseases, and the disease control rate was 70%. Median overall survival and time-to-progression were 5.9months (95% CI, 3.9-11.3months) and 3.6months (95% CI, 2.2-4.2months), respectively. Grade 3/4 toxicities included leucopenia (35%), neutropenia (35%), anemia (20%), and thrombocytopenia (15%). Two patients treated for approximately 1year developed cisplatin-related toxicities. In conclusion, gemcitabine and cisplatin combination chemotherapy produces a limited tumor response in BTC, but may prolong patient's survival.

Phase II study of fixed dose-rate infusion of gemcitabine and UFT combination chemotherapy in patients with advanced bile duct cancer: Daegu Gyeoungbuk Oncology Group.

e14547 Background: This phase II study evaluated efficacy of fixed dose rate (FDR) infusion of gemcitabine (10 mg/m2/min) and UFT combination in chemo-naïve patients with advanced bile duct cancer. Methods: This was an open-label, single-arm, multicenter, phase II study with a Simon two-stage minimax design. Patients received the FDR gemcitabine 1,000 mg/m2 for 3 consecutive weeks and UFT 400 mg/m2 on days 1-21. The cycle was repeated every 28 days. The primary end point was Response Evaluation Criteria in Solid Tumors (RECIST)-defined objective response rate. Secondary end points included clinical benefit response (CBR), safety, progression-free survival (PFS), and overall survival (OS). Clinical characteristics including four single nucleotide polymorphisms in DNA repair genes (RecQ1, RAD54L, XRCC1, ATM) were evaluated whether these influence the overall survival. Results: Between December 2006 and February 2008, fifty-one patients were enrolled, with a median age of 58 years. The majority of patients (76%) had intra-hepatic disease. Fourteen patients (27%) had a RECIST investigator- assessed, partial response (PR); disease control rate (PR + stable disease) was 55%. CBR was 14% among 37 evaluable patients. Hematologic toxicity was main grade 3 or 4 treatment-related adverse events. Median PFS was 4.0 months (95% CI, 2.9 to 5.1 months). Median OS was 7.0 months (95% CI, 3.5 to 10.5 months). Intrahepatic disease, poor performance, and, XRCC1 R194W C/C type were predictive markers of poor overall survival. Conclusions: FDR gemcitabine and UFT demonstrated apparent activity in patients with advanced bile duct cancer. However, this activity did not translate to prolong survival. The location of disease, performance status, and, polymorphic variants of DNA repair genes may affect clinical outcome of patients with advanced bile duct cancer. No significant financial relationships to disclose.