Gemcitabine Combination Chemotherapy Research Articles

Phase II study of gemcitabine and vinorelbine as second- or third-line therapy in patients with primary refractory or platinum-resistant recurrent ovarian and primary peritoneal cancer by the Korean Cancer Study Group (KCSG)_KCSG GY10-10

ObjectiveThe main aim of this study was to evaluate the antitumor activity and safety of vinorelbine and gemcitabine combination chemotherapy in patients with primary refractory or recurrent platinum-resistant epithelial ovarian and primary peritoneal cancers. MethodsPatients with platinum-resistant or primary refractory disease were eligible. Patients were allowed one prior chemotherapy for the treatment of platinum-resistant or refractory disease. Vinorelbine 25mg/m2, followed by gemcitabine 1000mg/m2, was administered intravenously on days 1 and 8 every 3weeks. Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 and cancer antigen 125 test (CA-125 criteria) were adopted to classify responses. Results44 patients received the median of 4 (range, 1–24) treatments with fifteen (34.1%) receiving six or more cycles. The overall objective response rate was 22.7%. One patient (2.3%) had complete while 9 patients (20.4%) had partial responses with median duration of response of 5.9months. 17 patients (38.6%) had stable disease for a median of 3.3months. Median progression-free survival (PFS) was 3.4months and overall survival (OS) was 14.5months. Four (9.1%) patients were not assessable. Neutropenia was the most frequently encountered toxicity, with grade 3 or 4 observed in 22 patients (50.0%). Fifteen patients (34.1%) needed immediate dose reduction. No treatment related death was reported. ConclusionsThe combination chemotherapy with gemcitabine and vinorelbine achieved the primary end point of our clinical trial in management of platinum resistant recurrent ovarian cancer. However, further sophisticated dosing and scheduling of combination chemotherapy are needed because of a significant proportion of dose reduction.

O1-8-4 - Phase 2 Trial of Gemcitabine Plus Uft in Oxaliplatin, Irinotecan and Fluoropyrimidine-Refractory Colorectal Cancer

Purpose: To investigate the efficacy of gemcitabine plus UFT (uracil-tegafur) combination chemotherapy as salvage treatment in patients with metastatic or relapsed colorectal cancer (MRCRC).Methods: This single-arm phase 2 study was conducted at 3 institutions in Korea. Patients with MRCRC refractory to fluoropyrimidine, oxaliplatin and irinotecan were enrolled. Gemcitabine 800 mg/m2 was administered intravenously on days 1, 8 and 15. UFT 200 mg/m2/day was taken orally in 3 divided doses on days 1-21. Cycles were repeated every 4 weeks and tumor evaluation was carried out every 8 weeks. The primary endpoint of this study was 8-week progression-free survival (PFS) rate.Results: Forty-one patients were enrolled. Fourteen patients received gemcitabine/UFT as a third-line treatment and 37 patients as a 4th-line or later-line therapy. Toxicities were easily manageable and non-hematologic toxicities of ≥ grade 3 were rare. The most common toxicity of ≥ grade 3 was neutropenia (20.0%). One patient showed partial response (response rate, 2.4%) and 14 (34.1%) showed stable disease. The 8-week PFS rate was 42.3%. The median PFS was 1.7 months [95% confidence interval (CI), 1.6-1.8 months] and the median OS was 9.2 months (95% CI, 5.8-12.6 months).Conclusions: Overall efficacy of gemcitabine/UFT in refractory MRCRC was unsatisfactory. However, we could found a minor proportion of patients who showed prolonged tumor stabilization to gemcitabine/UFT. Further studies are warranted to identify a patient subgroup that might have benefits from gemcitabine/fluoropyrimidine therapy.

Abstract 2821: Dual-label microdosing approach to identify chemoresistance to carboplatin and gemcitabine combination chemotherapy

Abstract Gemcitabine is commonly given in combination with cisplatin or carboplatin (GC therapy) as the first-line chemotherapy regimen for several malignancies, including bladder cancer. Unfortunately, less than half of patients respond to the therapy, generating a critical need for a test that predicts tumor response to GC therapy. The goal of this project is to measure drug-DNA adducts after administration of a single non-toxic microdose of gemcitabine in combination with carboplatin and correlating the degree of modification to chemotherapy sensitivity. We have previously shown that resistance to carboplatin may be identified by using a [14C]carboplatin microdose (1% of therapeutic dose), and subsequent measurement of the [14C]-DNA adducts via accelerator mass spectrometry (AMS), an ultrasensitive method used for detecting rare isotopes. We postulate that adduct levels induced in tumors by GC microdoses are proportional to those formed during full dose chemotherapy. Furthermore, we hypothesize that there exists a threshold level of adducts above which tumors respond to GC therapy. We used bladder cancer cell lines and the nod scid gamma severe combined immunodeficient (NSG) mice containing patient-derived tumor xenografts (PDX) from bladder cancer patients to determine GC-DNA adduct levels using AMS. The NSG mouse is uniquely capable of accepting and propagating tumor tissue engrafted directly from patient biopsy samples. The resulting groups of mice each have identical tumors, but can be treated in a variety of ways with replicate experiments; characteristics that are impossible to achieve in normal clinical studies. We will report progress on developing protocols and preliminary GC microdosing data using the NSG-PDX mouse model of human bladder cancer. Citation Format: Maike Zimmermann, Tiffany M. Scharadin, Hongyong Zhang, Tzu-yin Lin, Ralph W. deVere White, Chong-xian Pan, Paul T. Henderson. Dual-label microdosing approach to identify chemoresistance to carboplatin and gemcitabine combination chemotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2821. doi:10.1158/1538-7445.AM2014-2821

Second-line systemic treatment for advanced cholangiocarcinoma.

Gemcitabine plus platinum (GEM-P) combination chemotherapy is standard treatment for first-line advanced cholangiocarcinoma (aCC). GEM-P first-line therapy reports a progression-free survival (PFS) of 8 months and overall survival (OS) of 11.7 months. Treatment in the second-line setting is less clear. Five-year survival for aCC remains dismal at 5-10%. The purpose of this study was to describe the outcomes with second-line systemic treatment at our institution. This study was a single institution retrospective chart review of aCC patients who initiated second-line systemic treatment during 1/1/2009 to 12/31/2012. The primary objective was to evaluate PFS with second-line systemic treatment. Secondary objectives were OS and disease control rate. Second-line systemic regimens were classified into four treatment groups: GEM-P, gemcitabine + fluoropyrimidine (GEM-FU), other FU combination (FU-combo), and others. Fifty-six patients were included and the majority had intrahepatic aCC. A total of 80% received first-line gemcitabine-based therapy. Second-line therapy consisted of GEM-P (19.6%), GEM-FU (28.6%), FU-combo (37.5%), and others (14.3%). Median PFS was 2.7-month (95% CI, 2.3-3.8 months) with a median OS of 13.8 months (95% CI, 12-19.3 months) and a disease control rate of 50%. No significant difference in survival was identified between the four treatment groups. This study revealed a 2.7-month PFS, 50% disease control rate, and potential survival benefit with second-line treatment. Options for second-line systemic therapy include GEM-FU, FU-combo, GEM-P if not given in the first-line setting. Targeted therapy with erlotinib or bevacizumab could be considered in addition to chemotherapy.

Effectiveness of gemcitabine, pegaspargase, cisplatin, and dexamethasone (DDGP) combination chemotherapy in the treatment of relapsed/refractory extranodal NK/T cell lymphoma: a retrospective study of 17 patients.

The prognosis of extranodal nature killer (NK)/T cell lymphoma (ENKL) is dismal because of its aggressive course and multidrug resistance. Currently, for patients with relapsed/refractory ENKL, L-asparaginase-based regimens such as L-asparaginase, ifosfamide, methotrexate, etoposide, and dexamethasone (SMILE) or L-asparaginase, methotrexate, and dexamethasone (AspaMetDex) are recommended. We retrospectively investigated the efficacy and safety of gemcitabine, pegaspargase, cisplatin, and dexamethasone (DDGP) combination chemotherapy in the treatment of 17 relapsed/refractory ENKL patients. Clinical data from these patients were collected and analyzed. The primary end point was overall response rate (ORR). All patients were subjected to 2 to 6 cycles of DDGP chemotherapy, and the median number of cycles of DDGP regimen administrated was four. The ORR was 88.2 % (15/17), with nine patients (52.9 %) achieved complete response (CR) and six patients (35.3 %) achieved partial response (PR). The median follow-up time was 17 months (range 2-28 months). The 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) were 82.4 and 64.7 %, respectively. For those CR responders, the median PFS was 17 months. Grade 3/4 neutropenia occurred in nine patients (52.9 %) and grade 3/4 thrombocytopenia occurred in six patients (35.3 %). DDGP combination chemotherapy produces favorable outcomes in relapsed/refractory ENKL, and more attention should be paid to treatment-related myelosuppression. Further prospective trials are expected to define the efficacy.

A phase II study of gemcitabine, oxaliplatin, and erlotinib (GEMOX-T) combination chemotherapy in previously untreated patients with locally advanced unresectable or metastatic pancreatic cancer.

e15260 Background: In a phase III trial, the addition of erlotinib to gemcitabine improved the survival in advanced pancreatic cancer compared with gemcitabine alone. In addition, gemcitabine in co...

Efficacy and toxicity of FOLFOX-4 as a second-line chemotherapy in locally advanced unresectable and metastatic carcinoma gall bladder: A prospective observational study.

e15101 Background: There is no standard second-line chemotherapy after progression on 1st line therapy Gemcitabine and platinum combination chemotherapy, in locally advanced (unresectable) and meta...

Second-line systemic treatment for advanced cholangiocarcinoma.

371 Background: Five-year survival for advanced cholangiocarcinoma (aCC) is reported at 5-10%. For advanced, unresectable patients, gemcitabine plus platinum (GEM-P) combination chemotherapy is common practice as first-line treatment with progression free survival (PFS) of 8 months and overall survival (OS) of 11.7 months. Data regarding chemotherapy treatment after first-line progression is limited. Methods: We performed a retrospective chart review of patients with aCC from 1/1/2009 to 12/31/2012 who received second-line chemotherapy at M.D. Anderson Cancer Center (MDACC). Median PFS was the primary endpoint. Secondary objectives included disease control rate (complete response + partial response + stable disease) and OS. Inclusion criteria: aCC diagnosis, progression on first-line therapy, and reimaging studies at MDACC. Exclusion criteria: patients who received localized treatment for aCC prior to second-line therapy or consolidative chemoradiation, mixed histology tumors, and those with a history of another malignancy. Results: 56 patients were identified, with the majority having intrahepatic aCC (95%). 80% of patients received gemcitabine based first-line treatment (GEM-P +/- erlotinib, GEM monotherapy). Second-line systemic treatment included GEM-P (19.6%), GEM + fluoropyrmidine (GEM-FU) (28.6%), fluoropyrmidine combination (FU-combo) (37.5%), and other consisting of chemotherapy or biotherapy monotherapy or combination (14.3%). Total median PFS was 2.7 months (95% CI = 2.3 to 3.8). Disease control rate was 50% with a median OS of 13.8 months (95% CI = 12 to19.3). No significant difference in PFS or OS was identified between the four second line treatment groups. A higher CA 19-9 at the start of second line treatment correlated with a worse survival (p= <0.01). Conclusions: This retrospective study revealed a 50% disease control rate, median PFS of 2.7 months, and a potential for improvement in OS in patients who received second line systemic treatment. Agents that may be considered include GEM + FU, FU-combination therapy, or GEM-P if not given first line.

First-Line Gemcitabine Plus Cisplatin in Nonsmall Cell Lung Cancer Patients

Aim. To evaluate the predictive value of RRM1, ERCCl, and BRCA1 expression in Chinese NSCLC patients treated with gemcitabine and cisplatin. Methods. Real-time fluorescent quantitative PCR was used to determine the RRM1, ERCC1, and BRCA1 mRNA expression levels of peripheral blood in late-stage NSCLC patients. The relationship between peripheral blood and mRNA expression in tumor tissues was analyzed further. Results. In terms of the tumor susceptibility to chemotherapy, the response rate in the low-RRM1-expression group was significantly greater than in the high-expression group (52.9% versus 5.9%, χ 2 test, P = 0.007). Subjects with low peripheral blood RRM1 expression survived longer than those with high RRM1 expression (15.5 versus 12.0 months, logrank 3.980, P = 0.046). Linear correlations were observed between peripheral blood and tumor tissue expression levels for RRM1 (R 2 = 0.045, P = 0.048) and BRCA1 (R 2 = 0.021, P = 0.001). Conclusion. Our study demonstrates increased survival and superior efficacy of gemcitabine and cisplatin combination chemotherapy in the treatment of NSCLC patients with low peripheral blood RRM1 expression. The linear correlations of the relative expression of mRNA were observed between peripheral blood and tumor tissue expression levels for RRM1 and BRCA1. RRM1 gene expression may contribute to chemotherapy sensitivity and may be an indicator of survival. It was significant to individual chemotherapy of patients with advanced NSCLC who do not have sufficient tumor tissue.

Genetic polymorphisms of SLC28A3, SLC29A1 and RRM1 predict clinical outcome in patients with metastatic breast cancer receiving gemcitabine plus paclitaxel chemotherapy

BackgroundPaclitaxel and gemcitabine (PG) combination chemotherapy is effective as a maintenance chemotherapeutic regimen in metastatic breast cancer (MBC) patients because it increases progression-free survival (PFS), which increases overall survival (OS). The primary purpose of our study was to investigate the association between genetic polymorphisms in the genes involved in PG pathways and clinical outcomes in MBC patients treated with PG chemotherapy. MethodsA total of 324 MBC patients were enrolled in this prospective multicenter trial of PG as the first-line chemotherapy. Eighty-five of the 324 patients from two institutes were available for analysis of single nucleotide polymorphisms (SNPs). Germline DNA was extracted from peripheral blood mononuclear cells. Thirty-eight SNPs in 15 candidate genes selected from pathways that may influence the metabolism and transport of, or sensitivity, to PG were analysed. ResultsThe median PFS and OS of all 324 patients were 8.7months (95% confidence interval [CI]: 7.5–9.6months) and 26.9months (95% CI: 23.6–30.1months), respectively. An SNP in SLC28A3 (rs7867504, C/T) was associated with OS (CC or CT versus TT: 37 versus 21months, p=0.027, hazard ratio [HR] 2.6, 95% CI: 1.1–6.3). SLC29A1 GA haplotype had a significantly shorter OS (p=0.030, HR 3.391, 95% CI: 1.13–10.19). RRM1 (ribonucleotide reductase large subunit M1) SNP (rs9937), and haplotypes ATAA and ATGA were significantly associated with neurotoxicity. ConclusionGenetic polymorphisms in SLC28A3, SLC29A1 and RRM1 can influence the clinical outcome of MBC patients treated with PG chemotherapy. Further studies on the functional mechanisms relating to these germline polymorphisms in these genes are warranted.

The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer.

In pre-clinical models, the only two chemotherapy drugs which have been demonstrated to directly reduce the number of myeloid-derived suppressor cells (MDSCs) are gemcitabine and 5-fluorouracil. Here we analyze the dynamics of MDSCs, phenotyped as Lin-DR-CD11b+, in patients with advanced pancreatic cancer receiving the combination of gemcitabine and capecitabine, a 5-FU pro-drug. We found no evidence that gemcitabine and capecitabine directly reduce MDSC% in patients. Gemcitabine and capecitabine reduced MDSCs in 42% of patients (n = 19) and MDSC% fell in only 3/9 patients with above-median baseline MDSCs. In 5/8 patients with minimal tumour volume change on treatment, the MDSC% went up: increases in MDSC% in these patients appeared to correlate with sustained cancer-related inflammatory cytokine upregulation. In a separate cohort of 21 patients treated with gemcitabine and capecitabine together with concurrently administered GV1001 vaccine with adjuvant GM-CSF, the MDSC% fell in 18/21 patients and there was a significant difference in the trajectory of MDSCs between those receiving GV1001 and GM-CSF in combination with chemotherapy and those receiving chemotherapy alone. Thus, there was no evidence that the addition of low-dose adjuvant GM-CSF increased Lin-DR-CD11b+ MDSC in patients receiving combination chemoimmunotherapy. 9/21 patients developed an immune response to GV1001 and the MDSCs fell in 8 of these 9 patients, 6 of whom had above-median pre-vaccination MDSC levels. A high pre-vaccination MDSC% does not preclude the development of immunity to a tumour-associated antigen.

Association between single nucleotide polymorphism (SNPs) of CYP3A4 and SLC28A3 and clinical outcome in metastatic breast cancer (MBC) patients receiving paclitaxel plus gemcitabine (PG) chemotherapy as first-line treatment.

1088 Background: Paclitaxel and gemcitabine (PG) combination chemotherapy is an effective regimen in metastatic breast cancer (MBC) patients as first-line chemotherapy. The primary purpose of our study was to investigate the association of the single nucleotide polymorphisms (SNPs) and clinical outcome in MBC patients treated with PG chemotherapy. Methods: A total of 324 MBC patients were enrolled in this prospective multicenter trial as the first-line chemotherapy. Eighty five of 324 patients were available for SNP analysis. Germline DNA from peripheral blood (PB) mononuclear cells was extracted. SNPs in 15 genes (27 SNPs) from pathways that may influence cellular sensitivity to paclitaxel and gemcitabine were genotyped from PB sample. Results: Median progression free survival (PFS) and overall survival (OS) of all 324 patients was 8.7 months (95% CI: 7.5-9.6 mo.) and 26.9 months (95% CI: 23.6-30.1 mo.), respectively. Among clinical parameters, young age (p = 0.047, HR 1.03 [95% CI, 1-1.07]), positive hormonal receptor status (p = 0.0004, HR 0.26 [95% CI, 0.12-0.54]), and hepatic metastasis (p = 0.046, HR 2.30 [95% CI, 1.02-5.18]) were identified predictive factors for OS in Cox-regression analysis. SLC28A3 SNP which participates in transcription showed correlation with OS. OS of the patients with CC and CT genotypes in SLC28A3 was significantly longer than the OS of the patients with TT genotype (median OS: 31 vs. 37 vs. 21 months, p = 0.027, HR 2.6 [95% CI, 1.1-6.3]). OS of the patients with TT genotype in CYP3A4 was significantly longer than the OS of the patients with TC genotype (median OS: 37 vs. 19 months, p = 0.021, HR 5.8 [95% CI, 1.3-25.7]). After adjusting hormonal receptor status, age, and hepatic metastasis, prognostic value of SLC28A3 remained significant (HR 2.9, p = 0.047). Other SNPs were not significantly associated with PFS, OS, or toxicities. Conclusions: SLC28A3 SNP can predict with the clinical outcome of MBC patients treated with PG chemotherapy. Further studies for functional mechanism of germline polymorphisms in SLC28A are warranted.

A Case of Common Bile Duct Cancer That Completely Responded to Combination Chemotherapy of Gemcitabine and TS-1

Common bile duct (CBD) cancer is a relatively rare malignancy that arises from the biliary epithelium and is associated with a poor prognosis. Here, we report a case of advanced metastatic CBD cancer successfully treated by chemotherapy with gemcitabine combined with S-1 (tegafur+gimeracil+oteracil). A 65-year-old male presented with pyogenic liver abscess. After antibiotic therapy and percutaneous drainage, follow-up computed tomography (CT) showed an enhanced nodule in the CBD. Biopsy was performed at the CBD via endoscopic retrograde cholangiopancreatography, which showed adenocarcinoma. Additional CT and magnetic resonance imaging showed multiple small nodules in the right hepatic lobe, which were confirmed as metastatic adenocarcinoma by sono-guided liver biopsy. The patient underwent combination chemotherapy with gemcitabine and S-1. After nine courses of chemotherapy, the hepatic lesion disappeared radiologically. Pylorus-preserving pancreaticoduodenectomy was performed, and no residual tumor was found in the resected specimen. Three weeks after the operation, the patient was discharged with no complications. Through 3 months of follow-up, no sign of recurrence was observed on CT scan. Gemcitabine combined with S-1 may be a highly effective treatment for advanced cholangiocarcinoma.

Phase II trial of first-line chemotherapy with gemcitabine, etoposide, and cisplatin for patients with advanced urothelial carcinoma

ObjectivesThis study sought to examine the combination chemotherapy of gemcitabine, etoposide, and cisplatin (GEP) as a first-line treatment for advanced urothelial carcinoma (UC) to assess its antitumor activity and toxicity. Methods and materialsEligible patients with advanced UC had undergone no previous chemotherapy. Advanced UC was defined as unresectable or metastatic disease. Subsequent recurrent disease, either locally or distantly following primary radical surgery, was not excluded. GEP was recycled every 4 weeks. Etoposide and cisplatin were given on days 1 through 3 at doses of 60mg/m2 and 20mg/m2, respectively, and gemcitabine was given on days 1, 8, and 15 at a dose of 800mg/m2. The primary end point was objective response rate, and the secondary end points included progression-free survival, overall survival (OS), and toxicity. ResultsForty-two patients were enrolled and subsequently treated with GEP. Nineteen had visceral/bone metastases, 16 had disease restricted to the lymph nodes, and the remaining 7 had unresectable disease at the primary site. The median number of GEP courses was 4. Thirty of the 42 assessable patients (71.4%, 95% confidence interval [CI]: 56.4%–82.8%) demonstrated objective responses. At a median follow-up of 14.6 months, median progression-free survival and OS periods were 8.7 months (95% CI: 6.9–14.6mo) and 16.2 months (95% CI: 13.1–25.4mo), respectively. In the multivariate analysis, anemia and visceral/bone metastasis were significant pretreatment prognostic factors for OS. Grade 4 hematologic events were neutropenia (83.3%), thrombocytopenia (23.8%), and anemia (7.1%). There were no toxic deaths and no instances of severe nonhematologic toxicity. ConclusionsGEP as a first-line chemotherapy treatment was very active and moderately tolerable for advanced UC. Anemia and visceral/bone metastasis were important negative predictive factors of GEP for OS.

P2-026 - The Combination Chemotherapy of Gemcitabine and Carboplatin–Bevacizumab in Patients with Advanced Non-Small-Cell Lung Cancer

ABSTRACT Background The addition of bevacizumab–paclitaxel and carboplatin showed significant benefits in progression-free survival and overall survival in patients with advanced non-small-cell lung cancer. We are conducting a prospective study about safety and efficacy of combination chemotherapy with gemcitabine and carboplatin–bevacizumab (GC + BV) in previously untreated patients with advanced or metastatic NSCLC. Methods Between April 2010 and January 2012, a total of 35 patients with recurrent or advanced NSCLC (stage IIIB or IV) were treated with the GC + BV regimen. The regimen consists of gemcitabine of 1000 mg/m2 on days 1 and 8, carboplatin of AUC 5 and bevacizumab of 15 mg/kg on day 1. Treatment repeats every 3 weeks up to six cycles, followed by bevacizumab until disease progression or intolerable toxicity. Results Thirty-four patients were male. The median age of patients was 68 (55–79) years. Twenty-six patients were stage IV or recurrent disesase and 9 were IIIB. Fifteen (69%) patients were adenocarcinoma (12, squamous cell carcinoma; 8, others). Twenty-four (68%) patients had ECOG PS of 0–1. The overall response rate was 46% with no complete response and 16 partial responses. Grade 3 and 4 neutropenia were 16 and 1%, respectively. Clinically significant hemorrhagic events were not identified till now. There was one treatment-related death (septic shock with neutropenia during the first cycle). Non-hematologic toxicities were mild and manageable, but two patients complained grade 3 general weakness and one patient experienced grade 4 pneumonia. The median PFS was 5.7 months (95% CI, 3.69–6.45 months). Conclusions The addition of bevacizumab–gemcitabine and carboplatin in the treatment of selected patients is effective and tolerable in NSCLC including squamous cell carcinoma. This is ongoing study and we present preliminary results.

768 - Gemox Plus Erlotinib for the Treatment of Metastatic Pancreatic Adenocarcinoma

ABSTRACT Introduction Based on demonstration of a significant improvement in overall survival in a placebo-controlled phase III trial, gemcitabine in combination with erlotinib has been approved for the treatment of metastatic pancreatic cancer. In patients with good performance status, gemcitabine combination chemotherapy, i.e. with oxaliplatin (GEMOX) is commonly being used. Although there is some evidence that GEMOX plus erlotinib is beneficial in a subgroup of patients compared to GEMOX alone in cholangiocellular carcinoma no such data exist for pancreatic cancer. Thus, we performed this retrospective analysis in unselected patients to investigate the efficacy and safety of this chemotherapy regimen. Patients and methods Forty-four patients with metastatic adenocarcinoma of the pancreas receiving off-protocol GEMOX in combination with erlotinib at a single institution between January 2006 and September 2011 were included in this analysis. Data collection included baseline demographic, clinical and toxicity data as well as objective response according to RECIST criteria, progression-free survival (PFS) and overall survival (OS). Results A total of 44 patients were included in this study. The mean age was 60.5 years, and the median ECOG performance score was 1 (range, 0-1). GEMOX in combination with erlotinib was first line regimen in 84% of the patients. Clinical response and disease stabilization was achieved in 45% of the patients. The median PFS was 4 months (range 0.5-43) and median overall survival was 9.6 months (range 0.7-54.7). However, the subgroup of 20 patients, who benefited from this regimen in terms of abrogation of progression, had a PFS of 11.2 and an OS of 15.4 months. Myelosuppression was the most frequent side effect. The most common severe nonhematological toxicity was diarrhea (5/44). Conclusions These data suggest that the combination of GEMOX plus erlotinib is safe and active in about half of the patients treated with this regimen. Identification of (bio)markers would be desirable in order to be able to select patients, who are most likely to benefit from this therapeutic strategy. Disclosure All authors have declared no conflicts of interest.

A Case of Metastatic Penile Cancer Showing a Prolonged Disease Free Survival of over Five Years After Cisplatin and Gemcitabine Combination Chemotherapy

This is the first reported case of prolonged survival of metastatic disease in penile cancer in a patient treated using this chemotherapy regime. Authors: Nowicki, Stefan; Hendry, David; Russell, John Corresponding Author: Stefan Nowicki, Beatson West of Scotland Cancer Centre, Glasgow, UK. Email: stefan.nowicki@ggc.scot.nhs.uk Introduction Penile cancer is a rare cancer in the […]

Biweekly combination therapy with gemcitabine and carboplatin compared with gemcitabine monotherapy in elderly patients with advanced non-small-cell lung cancer: A randomized, phase-II study

IntroductionThe strategy of chemotherapy in the elderly is controversial. We wanted to evaluate the efficacy and safety of biweekly gemcitabine and low-dose carboplatin combination therapy in elderly patients with advanced non-small-cell lung cancer (NSCLC). MethodsIn this phase-II trial, chemotherapy-naive elderly patients (aged ≥76 years) with NSCLC were randomly treated with biweekly combination therapy with gemcitabine and carboplatin (1000mg/m2 gemcitabine and carboplatin at an area under the curve (AUC) of 3 on days 1 and 15, every 4 weeks) or gemcitabine monotherapy (1000mg/m2 on days 1, 8 and 15, every 4 weeks). The primary endpoint was overall response rate and analysis was based on intention-to-treat. ResultsThirty-one patients were randomly assigned combination therapy and 30 were assigned monotherapy. The median age was 79.0 years. Response rate was 22.6% (95% confidence interval (CI): 11.4–39.8%) for biweekly combination therapy and 10.0% (95% CI: 3.5–25.6%) for monotherapy. Median progression-free survival in combination chemotherapy was 3.9 months (95% CI: 0.5–8.5 months), which was significantly longer that that in monotherapy (2.4 months, 95% CI: 0.5–6.7 months). The prevalence of hematological and non-hematological adverse events reaching grade 3/4 was not significantly different between combination therapy and monotherapy. ConclusionsBiweekly gemcitabine and low-dose carboplatin combination chemotherapy showed acceptable efficacy, toxicity, and tolerability in those aged ≥76 years with NSCLC. Further investigations with a large population are required to confirm our results.

Abstract 3705: Multicenter phase II clinical trial of gemcitabine and liposomal paclitaxel combination chemotherapy in patients with advanced biliary cancer

Abstract OBJECTIVE: Advanced biliary tract cancer is associated with a poor prognosis due to wide resistance to chemotherapeutic agents. This phase II clinical trial was conducted to determine the safety and efficacy of weekly gemcitabine and liposomal paclitaxel (Genexol-PM®) in patients with unrectable or metastatic biliary cancer. METHODS: The eligibility criteria were patients 1) with pathologically proven unresectable or metastatic biliary cancer, 2) with an ECOG performance status 0 to 2, 3) aged more than 18, 4) with measurable lesions, 5) with adequate hematologic, renal and liver functions, and 6) who provided written informed consent. Each treatment cycle was consisted of gemcitabine 1000 mg/m*2 and liposomal paclitaxel 100 mg/m*2 on days 1, 8 followed by rest perioid of 14 days. It was repeated until the appearance of disease progression or unacceptable toxicity up to maximal 9 cycles. The primary end point of this study was reponse rate, and secondary end points included toxicity, progression free survival and overall survival. RESULTS: Thirty five patients were enrolled; median age was 63 years; male (n=30) and female (n-10). The median number of cycles administered was 3.5 (range, 1-10). Thirty patients were assessable for efficacy. Nine partial responses and 16 stable diseases were confirmed. Giving an overall response rate was 35.6% and disease control rate was 55.6% in per-protocol population. Median overall survival was 12.3 months (95% CI: 5.79-18.74) and median progression free survival was 4.07 months(95% CI: 3.12-5.01). The most frequent adverse events (AE) of all grades were anemia and neutropenia (n=17) followed by leucopenia (13). Grade 3/4 hematologic AEs: anemia (n=6), neutropenia (n=11), thrombocytopenia (n=1). Grade 3/4 non-hematologic AEs: elevated liver function tests (n=3), hyperbilirubinemia (n=1) hyponatremia (n=1). CONCLUSION: Weekly gemcitabine combined with liposomal paclitaxel appears to be effective against advanced biliary cancers. Further randomized trials are needed to confirm this finding. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3705. doi:1538-7445.AM2012-3705

Targeted therapy for biliary tract cancers

Biliary tract cancers (BTCs) are a heterogeneous group of malignancies, with a historically poor prognosis as a whole. Until recently, the development of effective therapeutics was hampered by the relatively low incidence, heterogeneity in patients and tumors, and correspondingly poor clinical trial enrollments. With the publication of the landmark phase III ABC-02 trial demonstrating the superiority of gemcitabine and cisplatin combination chemotherapy, the landscape changed for the development of new agents. Despite this progress, there are currently no approved targeted agents for BTC. This review will focus on recent developments in targeted therapeutics, directed against several key signaling pathways in BTC, including epidermal growth factor receptor, angiogenesis, and the mitogen-activated protein kinase pathway. Data from recent phase I and II trials will be discussed, along with a preview of upcoming trials involving targeted therapies.