Gemcitabine Oxaliplatin Research Articles

ABCL-006 Azacytidine plus rituximab–gemcitabine–oxaliplatin as salvage treatment in patients with relapsed/refractory diffuse large B-cell lymphoma

ABCL-006 Azacytidine plus rituximab–gemcitabine–oxaliplatin as salvage treatment in patients with relapsed/refractory diffuse large B-cell lymphoma

Dual epigenetic agents plus rituximab-gemcitabine-oxaliplatin as salvage treatment in relapsed/refractory diffuse large B-cell lymphoma patients failure of salvage chemotherapy.

Refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) patients' failure of salvage chemotherapy had extremely worse prognoses. Herein, 14R/R DLBCL patients failed to salvage chemotherapy were exposed to dual epigenetic agents (Chidamide 30mg biw*2w and Decitabine 10mg/m2 qd*d1-d5) and sequential R-GemOx (rituximab 375mg/m2 qd d6; gemcitabine 1g/m2 d7, d14; and oxaliplatin 100mg/m2 d7) for further salvage chemotherapy. Finally, 11/14(78.6%) patients achieved overall response with 6/14(42.9%) achieving complete remission and 2-year overall survival (OS)/progression free survival (PFS) rate was 42.7%, extremely higher than reported previously. Further subgroup analysis demonstrated that 2-year OS/PFS rate was significantly higher in patients achieved complete/partial remission or with low international prognosis index (IPI 0-2) than that in patients with steady disease or high IPI (3-5). Common grade 3-4 adverse events were hematological toxicities. All toxicities were transient and reversible. Our report implicates that combination of dual epigenetic agents and R-GemOx is a safe and promising alternative for R/R DLBCL patients.

Outcomes of Front-Line Therapy for Adult T Cell Leukemia/Lymphoma: A Pooled Analysis of Two Institutions

Introduction: Adult T cell leukemia/lymphoma (ATLL) is an aggressive mature T cell neoplasm caused by Human T lymphotropic virus type 1/2 (HTLV1/2) infection. HTLV1/2 is endemic in several geographic areas such as Latin America, Japan and intertropical Africa with estimated 5-10 million individuals infected worldwide. There is no standard therapy for ATLL and most patients are treated with regimens used for aggressive lymphomas. We hereby reviewed the outcome of patients treated in two US academic medical centers with a high prevalence of ATLL. Methods: We retrospectively evaluated all of the patients with a confirmed diagnosis of ATLL seen in two academic medical centers in Florida, USA. Baseline characteristics, treatments regimens and clinical outcomes where evaluated. First line therapies were categorized as treatment with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), Intensive chemotherapy (HyperCVAD, VCAP-AMP-VECP, or EPOCH), vs others (Interferon and zidovudine, Gemcitabine Oxaliplatin, Pralatrexate, and Gemcitabine cisplatin dexamethasone). Patient and disease characteristics were compared using Chi-square. Progression free survival (PFS) and overall survival (OS) for different chemotherapy regimens were compared using log-rank testing. Results A total of 61 patients were included in the analysis. The median age was 58 (32-75) years. Two thirds of the patients were female. The majority were of African American descent (82.5%) (Table 1), and 35.6% were originally from Jamaica, followed by 13.6% from Haiti. Patients were more likely to have CR/PR to CHOP (72%) compared to those treated with intensive chemotherapy or others (27.3% and 29.4% respectively) (p=0.007) (figure 1A). While there was no statistically difference in baseline characteristics in patients receiving the three categories of treatments (i.e. age, stage, ECOG, CD30 status), patients with acute subtype were less likely to be treated with CHOP (21.1% vs 47.4% respectively, p=0.096) which might explain the discrepancies in response. There was no statistical difference in PFS and OS between the three CHOP, Intensive chemotherapy and others (6.4 mo, 3.1 mo, 2.1 mo, p=0.23) and (14 mo, 8.9 mo, 18.5 mo, p=0.14) respectively. Patients responding to first line therapy (CR/PR) had improved OS when compared to those having stable/progressive disease (15.9 mo vs 7.2 mo) (p=0.004) (Figure 1B). Conclusions: Our study results reflect the poor outcomes of ATLL patients, especially in the ones with primary refractory disease to frontline treatments. We also showed the suboptimal activity of frontline regimens for ATLL and lack of unifying therapeutic approach for this lymphoma in the US. Multi-institutional clinical trials exploring novel therapeutic frontline options to improve response rates, which translate in better OS are desperately needed in this population. Disclosures Sandoval-Sus: Massive Bio: Consultancy; Janssen: Consultancy; MorphoSys US: Consultancy; Celgene: Speakers Bureau. Sokol:Kymera Therapeutics: Membership on an entity's Board of Directors or advisory committees; Kyowa/Kirin Inc.: Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Consultancy, Honoraria, Speakers Bureau.

Presentation and Outcomes with First-Line Chemotherapy in Advanced Cholangiocarcinomas-A Relatively Rare Component of Biliary Tract Cancers in India.

Background Biliary tract cancers (BTCs) are a rare group of cancers with limited data with respect to advanced unresectable cholangiocarcinoma (CCA). Materials and Methods The study is a retrospective study of patients with advanced unresectable/metastatic CCA, who received first-line palliative chemotherapy (CT1) from January 2014 to March 2019 at the Tata Memorial Hospital, Mumbai. Baseline clinical characteristics, chemotherapeutic regimens, and toxicities were evaluated. Results One hundred and forty patients satisfied criteria for evaluation. Median age of the entire cohort was 57 years (range: 32–80). There were 87 patients (62.1%) with intrahepatic CCA, 35 patients (25%) with perihilar CCA, and 14 patients (10%) with distal CCA. One hundred and twelve patients (80%) had metastatic disease at presentation. Commonest CT1 regimens were gemcitabine–cisplatin (GC) in 89 patients (63.5%) and gemcitabine–oxaliplatin (GO) in 34 patients (24.3%). Sixty-three patients (45%) received second-line chemotherapy. With a median follow-up of 27 months, median progression-free survival for the entire cohort was 7.56 months (95% confidence interval [CI]: 6.23–8.88), and median OS was 12.16 months (95% CI: 10.08–14.24). Common chemotherapy-related grade 3/4 side effects included vomiting in 25 patients (17.9%), diarrhea in 23 patients (16.4%), and thrombocytopenia in 22 patients (15.7%). Conclusion The current study in advanced CCAs is the largest of its nature from India. The common regimens used as first line were GC and GO. Tolerance and overall survival appear similar to previously published data.

The Effect of Inflammatory Markers on Survival in Advanced Biliary Tract Carcinoma Treated with Gemcitabine/Oxaliplatin Regimen.

In advanced biliary tract carcinoma (BTC), the prognosis is very poor, and the overall survival is less than 1year. This study aimed to determine the effect of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), C-reactive protein (CRP)/albumin ratio (CAR), and prognostic nutritional index (PNI) on the survival of BTC patients treated with gemcitabine/oxaliplatin (GEMOX) regimen. Data of 53 patients with advanced BTC were evaluated retrospectively. Association between inflammatory markers and 6-month PFS and 12-month OS were compared by the log-rank test. The optimal cutoff values were determined by a receiver operating characteristic (ROC) curve analysis. NLR, dNLR, CAR, and PNI were grouped based on cutoff points 1.95, 1.15, 0.57, and 33, respectively. Univariate and multivariate analyses were used to assess their prognostic values for survival. Lower dNLR (< 1.15) was prognostic for higher 6-month PFS and 12-month OS rates, while lower NLR (< 1.95) was prognostic for higher 6-month PFS rates only. CAR and PNI did not have statistically significant effects on survival. Pretreatment dNLR and NLR values in advanced BTC can be used as predictive markers for survival in patients undergoing the GEMOX regimen.

A systematic review and network meta-analysis of adjuvant therapy for curatively resected biliary tract cancers.

Recent randomized controlled trials (rcts) have contributed high-quality data about adjuvant therapy in curatively resected biliary tract cancer (btc); however, a standard approach to treating those patients still has not been developed. We conducted a systematic review of published studies and abstracts up to and including June 2018, choosing rcts involving patients with btc receiving adjuvant chemotherapy after complete surgical resection. Network meta-analysis methods were used for indirect comparisons of overall survival (os) and relapse-free survival (rfs) for various adjuvant therapies. Five rcts were included in qualitative synthesis, and three rcts (bilcap, prodige 12-accord 18, and bcat) had data sufficient for inclusion in the meta-analysis. Results from the indirect comparison demonstrated no significant improvement in os for capecitabine compared with gemcitabine or with gemcitabine-oxaliplatin (gemox), the hazard ratios (hrs) being 0.82 [95% confidence interval (ci): 0.53 to 1.27] and 0.86 (95% ci: 0.56 to 1.34) respectively. Similarly, no significant improvement in rfs was observed for capecitabine compared with gemcitabine or gemox. Although in the present analysis, we found no statistically significant improvements in os or rfs for capecitabine compared with gemox or gemcitabine, capecitabine can-until further prospective trials are completed-be considered the standard of care in the adjuvant setting based on a single randomized phase iii study.

Second-line rituximab-bendamustine versus rituximab-gemcitabine-oxaliplatin in diffuse large B-cell lymphoma in the real world.

Aim: Despite long-term responses to first-line immunochemotherapy, many patients with diffuse large B-cell lymphoma (DLBCL) have relapsed/refractory disease. Second-line treatment options are available. However, a large proportion of patients are ineligible for transplantation/intensive therapy. Patients & methods: This observational study of 702 patients in the USA, who used second-line therapies for relapsed/refractory DLBCL, evaluated treatment patterns and overall survival (OS). The study focused on the OS outcome of patients receiving second-line rituximab-bendamustine or rituximab-gemcitabine-oxaliplatin. Results & conclusion: Rituximab-bendamustine and rituximab-gemcitabine-oxaliplatin were received by 4.6 and 1.4% of patients, respectively (N= 42/702). Median and 1-year OS rates were similar between regimens. Many of the 200 different treatment regimens observed in second line were modified versions of National Comprehensive Cancer Network regimens.

Clinical efficacy of GEMOX regimen combined with targeted therapy for advanced gallbladder cancer

Objective To evaluate the clinical efficacy of gemcitabine-oxaliplatin (GEMOX) regimen combined with targeted therapy for advanced gallbladder cancer. Methods The retrospective descriptive study was conducted. The clinical data of 21 patients with advanced gallbladder cancer who were admitted to the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine between January 2016 and December 2017 were collected, including 8 males and 13 females, aged from 28 to 80 years, with the age of (58±12)years. Patients received GEMOX regimen combined with targeted therapy. According to the results of gene test, patients selected tageted therapy with Cetuximab, Herceptin or Apatinib. Observation indicators: (1) gene test situations; (2) situations of GEMOX regimen combined with targeted therapy; (3) adverse reactions of GEMOX regimen combined with targeted therapy. Measurement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were described as M (range). Count data were represented as absolute number or percentage. The survival curve and rate were respectively drawn and calculated using the Kaplan-Meier method. The survival analysis was done using the Log-rank test. Results (1) Gene test situations: of 21 patients, 19 were confirmed as K-ras wild type, including 13 of single K-ras wild type, 4 of K-ras wild type combined with human epidermal growth factor receptor 2 (HER2), 2 of K-ras wild type combined with vascular endothelial growth factor receptor 2(VEGFR2); 5 were detected positive HER2, including 1 of single positive HER2, 4 of positive HER2 combined with K-ras wild type; 3 were detected positive VEGFR2, including 1 of single positive VEGFR2, 2 of positive VEGFR2 combined with K-ras wild type. Two and 19 patients had 0 and 1 of Eastern Cooperative Oncology Group score. (2) Situations of GEMOX regimen combined with targeted therapy: all the 21 patients underwent ≥ 2 courses of GEMOX regimen combined with targeted therapy. Among the 21 patients, 0, 4, 9 and 8 were respectively detected in the complete remission (CR), partial remission (PR), stable disease (SD) and disease progression (PD). Fourteen patients (13 of single K-ras wild type and 1 of K-ras wild type combined with positive VEGFR2) received GEMOX regimen combined with Cetuximab therapy, including 0 with CR, 4 with PR, 5 with SD and 5 with PD; 5 patients (1 of single positive HER2 and 4 of positive HER2 combined with K-ras wild type) received GEMOX regimen combined with Herceptin therapy, including 0 with CR, 0 with PR, 2 with SD and 3 with PD; 2 patients (1 of single positive VEGFR2 and 1 of positive VEGFR2 combined with K-ras wild type) received GEMOX regimen combined with Apatinib therapy, including 0 with CR, 0 with PR, 2 with SD and 0 with PD. The objective response rate was 19.0%(4/21) and disease control rate was 61.9%(13/21) in the 21 patients. The median onset time was 1.8 months in the 21 patients. The 3-, 6- and 9-month progression free survival (PFS) rates and median PFS time were respectively 90.5%, 71.4%, 58.5% and 10.7 months. The 6- and 12-month overall survival rates were respectively 90.2% and 58.6%, and median overall survival (OS) time was 15.5 months in the 21 patients. The PFS and OS time were 8.4 months and 10.4 months in the 7 patients combined with jaundice, 10.5 months and 14.8 months in the 14 patients without jaundice, with no statistically significant difference (χ2=0.868, 0.774, P>0.05). (3) Adverse reactions of GEMOX regimen combined with targeted therapy: the most common adverse events were skin rash and digestive tract reactions. No serious adverse event occurred during the therapy. All the adverse events were improved after symptomatic treatments. Conclusion GEMOX regimen combined with targeted therapy for advanced gallbladder cancer has good outcomes, less adverse reactions and higher safety. Key words: Biliary tract neoplasms; Gallbladder cancer; Chemotherapy; Targeted therapy; Efficacy; Safety

Treatment Patterns and Outcomes of Relapsed/Refractory Peripheral T-Cell Lymphoma (RR-PTCL) Patients Treated in the Community Oncology Setting

Introduction: The majority of PTCL cases are pathologically heterogeneous, aggressive and chemorefractory; nearly 70% of patients who undergo induction chemotherapy develop RR disease. Data on how RR-PTCL patients are managed outside of clinical trials and academic settings have not been adequately studied. Understanding how PTCL patients are treated in the real world allows better design of future clinical trials and refined development of novel therapies. This study aimed to describe contemporary treatment patterns, clinical characteristics, and overall survival (OS) among RR-PTCL patients treated in the US community oncology setting.Methods: We conducted a retrospective, observational cohort study of RR-PTCL patients treated between 1/1/2010-12/31/2016. Data were collected from patient medical records abstracted from 30 community oncologists across all geographic areas in the US (38% South, 22% West, 7% Midwest, 26% Northeast, and 7% unknown). Patient characteristics, treatment patterns, adverse events (AEs), physician-reported response to first- and second-line (1L, 2L) treatments, and date of death were collected. Descriptive statistics were calculated to summarize patient characteristics and study outcomes. Median (95% confidence interval [CI]) OS from RR disease was calculated by the Kaplan-Meier method.Results: We analyzed 200 RR PTCL patients (71% received CHOP, 20% received CHOEP, and 9% received another regimen as 1L systemic therapy). The majority (58%) were PTCL not otherwise specified (NOS), 61% were males, and median age was 62 years (range: 20-90) (Table). Overall response rate (ORR) to 1L treatment was 80% (CR, 54%; PR, 26%), and ORR to 2L treatment was 55% (CR, 31%, PR, 24%). Among all PTCL patients and among those with PTCL NOS, the OS (95% CI) from RR disease was 13.0 months (95% 7.0-not estimable) and 9.0 months (95% 6.0-not estimable), respectively (Figure). Median time to RR disease from 1L initiation was 12.9 months. Median durations of 1L and 2L treatments were 4.4 months and 3.7 months, respectively. Among those who continued to 2L therapy, 27% received brentuximab vedotin (2% in combination), 19% received ICE (carboplatin/cisplatin, ifosfamide, etoposide), 13% received romidepsin (2% in combination with pralatrexate), 10% received pralatrexate monotherapy, 7% received GEMOX (gemcitabine, oxaliplatin), and the rest (22%) received other 2L regimens or an unknown regimen (2%). After 1L initiation, only 14/200 (7%) received hematopoietic stem cell transplant (HSCT) and 28/151 (19%) after 2L. AEs resulting in a dose reduction, discontinuation, or hospitalization during 1L treatment and occurring among ≥10% included anemia (39%), thrombocytopenia (27%), neutropenia (23%), mouth sores (16%), diarrhea (15%), neuropathy (14%), febrile neutropenia (13%), and vomiting (10%).Conclusions: While response to 1L treatment in this cohort was high (80%), all developed RR disease (or died), for whom the prognosis remains poor. Very few patients underwent HSCT in any line of therapy. Our data demonstrate the unmet medical need for RR-PTCL patients and the need for novel therapies in the 1L setting. It also underscores the need to better understand factors leading to treatment selection and optimal treatment sequencing in the real world. [Display omitted] DisclosuresNabhan:Cardinal Health: Employment, Equity Ownership. Laney:Cardinal Health: Employment, Equity Ownership. Feliciano:Seattle Genetics: Employment, Equity Ownership. Lee:Cardinal Health: Employment. Klink:Cardinal Health: Employment, Equity Ownership.

ESHAP versus GEMOX in Management of Relapsed or Refractory Lymphoma: A Prospective Randomized Study

Background: There is lack of evidence about the best chemotherapy regimen in treatment of relapsed/refractory Hodgkin'slymphoma (HL) and aggressive non-Hodgkin’s lymphoma (NHL) lymphoma.Aim: To compare GEMOX (gemcitabine, oxaliplatin) with ESHAP (etoposide, methylprednisolone, cytarabine arbinoside,cisplatin) regimes as 2nd line in lymphomas.Methods: This was a prospective randomized study that included relapsed/refractory HL and aggressive NHL patientswho failed 1st line chemotherapy. After assessment for eligibility, patients were randomized to receive GEMOX orESHAP.Results: The study included 41 patients, 21 of them received GEMOX and 20 received ESHAP. The response rate did notdiffer significantly between the GEMOX and ESHAP arms (28.6% vs. 35%, p=0.793) as well as progression free survival(8.7 months vs. 6.6 months, p=0.711). By univariate analysis for the whole group, the response rate differed significantlyaccording to disease status at relapse, time to relapse, lactate dehydrogenase, International Prognostic Index (IPI) andsecondary age-adjusted IPI (2ry aa-IPI). Hematological toxicity was not statistically different between the two treatmentarms. GEMOX was associated with significantly less vomiting of any grade (p=0.013). Acute renal toxicity of any gradewas significantly lower in GEMOX compared to ESHAP (p=0.003). In terms of peripheral neuropathy, GEMOX wasassociated with significantly higher all grades (p=0.0001).Conclusion: The current study results suggest that the response rate and progression free survival of GEMOX and ESHAPare comparable with different toxicity profile.

Third line Treatment in Relapsed/Refractory Hodgkin's Lymphoma and Aggressive non-Hodgkin Lymphoma after 2nd line ESHAP or GEMOX

Background: Treatment after failure of 2nd line chemotherapy in patients with Hodgkin's lymphoma (HL) or aggressive non-Hodgkin’s lymphoma (NHL) is not well studied. Aim: To assess the value of 3rd line treatment in a cohort of HL and aggressive NHL patients. Methods: This was a retrospective study of patients with relapsed/refractory HL or aggressive NHL treated with 3rd line treatment based on physician choice. Response rate as well as overall survival (OS) and factors affecting it were assessed. Results: Fifteen (41%) out of 37 patients who failed 2nd line received 3rd line. The remaining 22 received single-agent palliative chemotherapy or best supportive care only. Third line treatment was IGEV (ifosfamide, gemcitabine, navelbine) in 7 (47%) patients, lenalidomide in 4 (26%), ESHAP (etoposide, methylprednisolone, cytosine arabinoside, cisplatin) in 2 (13%) and GEMOX (gemcitabine, oxaliplatin) in 2 (l3%). Four (27%) patients achieved complete remission (2 with IGEV and 2 with lenalidomide) and 3 of them underwent autologous stem cell transplantation. One (7%) patient achieved partial response and another one (7%) had stable disease. The median OS for the whole group was 4.7 months. For patients who received 3rd line the OS was significantly longer than those who didn’t (13.4 vs. 3.4 months, p=0.001). Among the whole set of patients, performance status, lactate dehydrogenase, tertiary age-adjusted International Prognostic Index, 3rd line treatment, response to 3rd line and transplantation had significant impact on OS.Conclusion: Third line treatment may be feasible in selected HL and aggressive NHL patients who failed 2nd line.

Successful treatment with GEMOX in patient with metastatic pancreatic adenosquamous carcinoma.

Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreatic cancer characterized by a dual histological component and aggressive behavior. This form is not well known, its histogenesis is uncertain, and there are different opinions on the diagnostic histopathological criteria. The differential diagnosis with more common ductal adenocarcinoma, squamous cell carcinoma, squamous or adenosquamous metastases is complex. The available therapies do not improve the poor prognosis and it is difficult to find long-term survivors (more than 1 year), even after demolitive surgery with complementary therapies. We report a case of advanced PASC with excellent progression-free survival and overall survival, 20 months and 29 months, respectively. Furthermore, an almost complete response was obtained to first-line chemotherapy with gemcitabine/oxaliplatin (GEMOX) followed by maintenance gemcitabine. GEMOX followed by gemcitabine as maintenance could be an effective treatment for this pancreatic entity. Further reports are needed to confirm this outcome.

Optimal therapy for patients with hepatocellular carcinoma and resistance or intolerance to sorafenib: challenges and solutions.

The only US Food and Drug Administration (FDA)-approved first-line systemic therapy for hepatocellular carcinoma (HCC) is sorafenib; however, resistance or intolerance to sorafenib is unfortunately common. In this review, we briefly describe systemic therapies that can be considered for patients with HCC who show resistance or intolerance to sorafenib. For all patients with HCC who need systemic therapy, we strongly advocate for participation in clinical trials. Cytotoxic chemotherapy plays a minor role in the treatment of advanced HCC, with some data supporting the use of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) and GEMOX (gemcitabine-oxaliplatin). Multi-target kinase inhibitors such as lenvantinib and regorafenib have recently met their primary endpoints as first- and second-line therapy, respectively, with regorafenib now representing the only FDA-approved drug for second-line treatment of HCC. Other targeted therapies remain under investigation, but results so far have not significantly changed clinical practice. Immunotherapy is an interesting area of research in the treatment of HCC with preclinical and early clinical data demonstrating exciting results; thus numerous investigational studies are currently focusing on immunotherapy in the treatment of HCC. While systemic treatment options in HCC remain a challenge for providers, in this review, we summarize the current literature and highlight areas of progress with respect to the treatment of patients with HCC and resistance or intolerance to sorafenib.

Gemcitabine-cisplatin versus gemcitabine-oxaliplatin doublet chemotherapy in advanced gallbladder cancers: a match pair analysis.

Gemcitabine-cisplatin (GC) and gemcitabine-oxaliplatin (GO) are the most commonly used regimens in advanced gallbladder cancer (GBC). The data of patients with advanced GBC, treated between January 2013 and June 2015 were retrieved. A 1:1 matching without replacement was performed by using nearest neighbor matching method. A total of 326 patients (163 GC and 163 GO), were matched 1:1 by age and gender. The response rates for GC and GO were 31.2% and 36.3% (P = 0.350). The overall median event free survival (EFS) was 4.34 months (95% CI 4.030-4.644 months). The median EFS was 4.67 months (95% CI 4.060-5.271 months) in GC cohort and 3.88 months (95% CI 3.369-4.385 months) in GO cohort (P = 0.023). The overall median OS was 8.016 months (95% CI 7.361-8.672 months). The median OS was 8.02 months (95% CI 7.257-8.776 months) in GC cohort and 7.79 months (95% CI 6.690-8.88 months) in GO cohort (P = 0.455). The incidence of Grade 2/3 peripheral neuropathy (9.2% vs. 3.1%; P = 0.445) and Grade 3/4 transamintis (14.7% vs. 6.1%) was higher with GO while the incidence of anemia (22.1% vs. 6.7%; P < 0.001), neutropenia (7.3% vs. 2.4%; P = 0.49) and thrombocytopenia (9.8% vs. 3.7%; P = 0.033) was higher with GC. Gemcitabine-cisplatin or gemcitabine-oxaliplatin can be used as an initial regimen in advanced GBC. Higher EFS, potentially lower costs, lower incidence of peripheral neuropathy and hepatotoxicity favor the use of GC, whereas a lower incidence of hematological toxicities, and potential ease of administration in patients with borderline renal and cardiac functions favor GO.

Treatment of advanced Gall bladder cancer in the real world-can continuation chemotherapy improve outcomes?

Gemcitabine-Platinum doublet chemotherapy is the standard of care in patients with locally advanced inoperable and metastatic (LA/M) Gall bladder cancers (GBC). Consecutive patients with LA/M GBC treated with Gemcitabine-Cisplatin (GC) or Gemcitabine-Oxaliplatin (GO) as first line palliative chemotherapy from January 2013 to June 2015 were retrospectively analysed. Patients who were able to continue chemotherapy beyond 6-8 cycles were separately compared to those who were potential candidates for this approach, but chose not to continue chemotherapy. A total of 396 patients received first line palliative chemotherapy during the period of analysis, 276 patients (69.6%) were unable to complete 6-8 cycles of chemotherapy, while 120 patients (30.4%) were potential candidates for continuing chemotherapy. Seventy patients (n=120; 58.3%) received a median of 4 cycles of continuation chemotherapy. Median overall survival (OS) for the entire cohort was 7.65 months [95% confidence interval (CI), -7.14 to 8.16], while median event free survival (EFS) was 4.53 months (95% CI, -4.23 to 4.83). Patients receiving continuation chemotherapy had a statistically improved median OS compared to all other patient cohorts, 14.88 months (95% CI, -12.48 to 17.27; P=0.005 on multivariate analysis). Burden/number of sites of metastases, receiving of continuation chemotherapy, fit and able to receive second line chemotherapy (CT2) were identified on multivariate analysis as prognostic factors for OS. OS in our study appeared lower than published literature, but a group of patients were identified whose survival could be prolonged by continuing chemotherapy. Easily available factors can predict prognosis of GBC undergoing first line palliative chemotherapy.

Neutrophil/lymphocyte ratio helps select metastatic pancreatic cancer patients benefitting from oxaliplatin.

High Neutrophil/Lymphocyte ratio (NLR), as a measure of enhanced inflammatory response, has been negatively associated with prognosis in patients with localized pancreatic ductal adenocarcinoma (PDA). In the present study, we aimed at investigating the prognostic value of NLR in two homogeneous groups of chemotherapy-naïve metastatic PDA patients. Patients were treated with either gemcitabine (GEM) or gemcitabine/oxaliplatin (GEMOXA). We also assessed whether NLR could identify patients benefiting from the use of oxaliplatin. Consecutive PDA patients treated at the Medical Oncology Unit of Tor Vergata University Hospital of Rome with either GEM or GEMOXA were included (n= 103). NLR was assessed before and during chemotherapy and correlated with outcome together with common clinical and biochemical variables. Among 17 analyzed variables NLR, Karhofsky Perfomance Status (KPS), d-dimer and erythrocyte sedimentation rate were found to be significantly associated with median Overall Survival (mOS) at the univariate analysis. Only NLR and KPS were independent prognosticator at multivariate analysis, with NLR displaying the highest statistical significance. NLR was also predictive of oxaliplatin activity, as only patients with NLR > 2.5 (cutoff determined upon ROC analysis) derived benefit from GEMOXA over GEM. NLR is both an independent prognostic and predictive factor in metastatic PDA, since only patients with high NLR seem to benefit from the addition of oxaliplatin. NLR may help select patients for whom a particularly poor prognosis might justify more intensive, yet less tolerable, combination regimens.

Efficacy of a sequential treatment strategy with GEMOX-based followed by FOLFIRI-based chemotherapy in advanced biliary tract cancers

Background: Gemcitabine (GEM)-platinum chemotherapy stands as first-line therapy for patients with recurrent/advanced biliary tract cancer (BTC), yielding progression-free survival (PFS) of 3.4–6.4 months. No standard second-line chemotherapy after GEM-platinum failure exists and data on survival benefit remain limited.Material and methods: We retrospectively reviewed patients with recurrent/advanced BTC who received gemcitabine-oxaliplatin (GEMOX)-based chemotherapy followed by 5-fluorouracil-irinotecan (FOLFIRI)-based chemotherapy to evaluate the efficacy of the sequential treatment strategy. Overall survival (OS) and PFS were calculated by Kaplan–Meier method.Results: Fifty-two patients were analyzed, 21 (40%) had intrahepatic, 14 (27%) had hilar/extrahepatic, and 17 (33%) had gallbladder cancer. Median age was 64 years (range 38–79 years). Prior curative intent resection of the primary tumor was performed in 23 (44.2%) patients and GEMOX adjuvant chemotherapy was given in 12 (23.1%) patients. After a median follow-up of 36.3 months, 47 (90.4%) patients completed the treatment strategy. First-sequence GEMOX and second sequence FOLFIRI achieved 4.8 months and 3.2 months median PFS, respectively. The global OS for the sequential chemotherapy was 21.9 months. The sequence of FOLFIRI resulted in a median OS of 8.4 months.Conclusion: The sequence of GEMOX-FOLFIRI is a potential treatment strategy for patients with recurrent/advanced BTC.

Gemcitabine–oxaliplatin (GEMOX) for epithelial ovarian cancer patients resistant to platinum-based chemotherapy

BackgroundPatients with platinum-resistant epithelial ovarian cancer (EOC) experience poor outcome. Currently, no clearly superior management strategy exists for platinum-resistant EOC patients. PurposeAnalyze the efficacy and safety of gemcitabine–oxaliplatin (GEMOX) in platinum resistant EOC patients. Patients and methodsThirty-two patients with platinum-based resistant EOC were included. Studied patients had received GEM at the dose of 1000mg/m2 on days 1 and 8 and OX 100mg/m2 on day 1, administered over 2h 30min after GEM infusion of 3week treatment cycle. ResultsIn the evaluation of tumor response, none of patients had achieved CR while PR, SD, were observed in 7 (21.9%), 9 (28.1%) respectively, clinical benefit (CR+PR+SD) was recorded in 50% of patients while PD was observed in 16 (50%) patients. In regard to survival, the median value of OS was 10.5months (range, 2.2–17.5months). The median value of PFS was 6.37months (range, 1–17.5months). The one-year OS rate was 34.4% and the one-year PFS rate was 12.5%. Concerning hematological toxicity grade 3 neutropenia was recorded in 4 (12.5%) patients while grade 4 febrile neutropenia was recorded in 2 (6.3%) patients and grade 4 anemia was represented by 3.1%. Grade 1–2 fatigue was the most common non-hematological toxicity and represented by 65.6% of patients. Grade 3 non hematological toxicity was recorded with nausea/vomiting and hepatic toxicity represented by 3.1% for both. ConclusionThe GEMOX combination is a regimen with a moderate therapeutic efficacy and tolerable toxic side effects in patients with platinum-resistant EOC.

Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors

Purpose: The role of chemotherapy in low-/intermediate-grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs. Methods: Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR + SD (partial response + stable disease) at 6 months, progression-free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling index, grade of differentiation and excision- repair-cross-complementing group 1 (ERCC-1) were analyzed in tissue tumor samples. Results: Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19 and unknown in 10% of patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of the patients were metastatic, and 87% were pretreated and progressive to previous therapies. Sixty-five percent of the patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), and 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). PR occurred in 26% of the patients, half of them with pancreatic NETs, and SD in 54%. With a median follow-up of 21 months, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical overexpression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome. Conclusion: This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8-month PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary tumors.

Clinical efficacy of pegaspargase plus GEMOX regimen for initial treatment of nasal NK/T-cell lymphoma

Objective: To evaluate the efficacy and safety of pegaspargase plus GEMOX (pegaspargase, gemcitabine, oxaliplatin) regimen in the initial treatment of nasal NK/T-cell lymphoma. Methods: Twelve preliminarily diagnosed nasal NK/T-cell lymphoma patients in Tianjin Medical University Cancer Institute and Hospital from June 2011 to March 2012 were analyzed. All patients took the pegaspargase plus GEMOX regimen (gemcitabine 800-1 000 mg/m on days 1 and 8, oxaliplatin 130 mg/m on day 1, and pegaspargase 2 500 IU/m on day 2), every three weeks for one cycle. The efficacy and toxicity of the regimen were evaluated in the follow-up treatment. Results: After two cycle treatments, 1 patient dropped out of treatment because of acute pancreatitis; the remaining 11 patients had response, in which 1 achieved complete response , 7 had partial response, 2 had stable disease, and 1 had progressive disease. The objective response rate was 72.7%, and the disease control rate was 90.9%. The 2-year overall survival rate was 90.9%. With median 6-cycle P-GEMOX regimen treatment, 81.8% of 11 patients presented side effects, primarily myelosuppression and hepatic dysfunction. Conclusion: Pegaspargase plus GEMOX regimen showed high efficacy on the initial treatment of nasal NK/T-cell lymphoma patients, but the incidence of adverse effect was still high.