Single-agent gemcitabine in patients with advanced, pre-treated angiosarcoma: A multicenter, retrospective study.

Gemcitabine has shown clinical activity against angiosarcoma in small series, alone, or combined with taxanes. We aimed to evaluate its activity as a single-agent in a larger series of patients with advanced angiosarcoma. We retrospectively reviewed the electronic medical records of consecutive adult patients with advanced angiosarcoma treated with single-agent gemcitabine at our institutions from January 2010 to January 2021. Response was evaluated according to RECIST 1.1, and toxicity was graded according to NCI-CTC v5.0. 42 patients were identified. 38 patients (90%) had received prior anthracyclines and weekly paclitaxel, and 9 (21%) had received pazopanib. The best tumor response was partial response (PR) in 16 patients (38%), or stable disease (10 patients, 24%). All 8 patients with cardiac angiosarcoma experienced a PR. Median PFS was 5.4 months (95%CI: 3.1-6.5), and median OS was 9.9 months (95%CI: 6.6-13.4). Single-agent gemcitabine has clinically meaningful activity in advanced, heavily pre-treated angiosarcoma.

Efficacy and Safety of Anti-PD-1 Immunotherapy in Patients With Advanced NSCLC With BRAF, HER2, or MET Mutations or RET Translocation: GFPC 01-2018.

INTRODUCTION: Immune-checkpoint inhibitor (ICI) efficacy in patients with NSCLC harboring molecular alterations remains poorly elucidated. This study was undertaken to determine ICI efficacy against BRAF-, HER2-, MET-, and RET-NSCLC in a real-world setting. METHODS: In this retrospective, multicenter study in ICI-treated BRAF-, HER2-, MET- or RET-NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS). RESULTS: There were 107 patients with NSCLC (mean age, 65.5 y) included from 21 centers: 37% were never-smokers, 54% were men, and 93% had adenocarcinoma. Among them, 44 had BRAF mutation (V600: 26), 23 had HER2 mutation, 30 had MET mutation, and nine had RET translocation. Programmed cell death ligand 1 (PD-L1) status was known for 70 patients and was greater than or equal to 1% in 34 patients. Before ICI, patients had received a median of one treatment line. Median duration of response, PFS, and OS were 15.4 (95% confidence interval [CI]: 12.6-not reached [NR]) months, 4.7 (95% CI: 2.3-7.4) months, and 16.2 (95% CI: 12.0-24.0) months, respectively, for the entire cohort. The response rates for BRAF-V600, BRAF-non-V600, HER2, MET, and RET-altered NSCLC were 26%, 35%, 27%, 36%, and 38%, respectively. For patients who were PD-L1 negative and those who were PD-L1 positive, PFS was 3.0 (95% CI: 1.2-NR) and 4.3 (95% CI: 2.1-8.5) months, respectively, and OS was 11.7 (95% CI: 4.1-NR) and 35.8 (95% CI: 9.0-35.2) months, respectively. Toxicities were reported in 28 patients (26%), including 11 patients (10%) with a grade greater than or equal to three. CONCLUSIONS: In this real-world setting, ICI efficacy against patients with BRAF-, HER2-, MET-, or RET-NSCLC seemed close to that observed in unselected patients with NSCLC. Large prospective studies on these subsets of patients are needed.

Four-arm robotic lung resection versus muscle-sparing mini-thoracotomy: retrospective experience.

BACKGROUND: Robotic surgery was introduced in the early 2000s but its use remains limited, particularly in thoracic surgery. Here we compare the first consecutive 185 four-arm robotic procedures carried out in our institution vs. muscle-sparing video-assisted mini-thoracotomy (MSMT), our previous minimally invasive approach for anatomical lung resection. METHODS: One hundred and eighty-five consecutive patients undergoing surgery using the four-arm robotic technique between February 2014 and December 2016 were compared to a control historical series of 136 consecutive patients undergoing surgery by MSMT in the same institution. The same senior surgeon performed all surgical procedures. Comparisons between the two groups were performed using the Chi2 test for qualitative data and the Wilcoxon, Mann-Whitney or Student's t-test for quantitative data. RESULTS: The demographic and clinical characteristics of the patients were similar in the two groups. In the robotic group, median (min-max) length of hospital stay (LOS) was significantly shorter (by 2 days) than in the MSMT group {7 days [3-63] vs. 9 days [5-63], respectively; P<0.0001}. The rate of complications was similar in the two groups, but the complications appeared to be less severe in patients undergoing robotic surgery (switch from Clavien-Dindo grade III and IV to grade II) although further studies are required to confirm this due to the large number of missing data. CONCLUSIONS: In a senior thoracic surgery practice, the switch from a minimally invasive technique to robotic surgery was safe and beneficial in patients undergoing anatomical lung resection in terms of LOS and possible complication severity.

Switch from abiraterone plus prednisone to abiraterone plus dexamethasone at asymptomatic PSA progression in patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: To evaluate the effects of switching from prednisone (P) to dexamethasone (D) at asymptomatic prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). MATERIALS AND METHODS: Among 93 patients treated with AA between January 2013 and April 2016 in our institution, 48 consecutive asymptomatic patients with mCRPC, who experienced biochemical progression on treatment with AA+P 10 mg/day, were included. A corticosteroid switch to AA+D 0.5 mg/day at PSA increase was administered until radiological and/or clinical progression. The primary endpoint was progression-free-survival (PFS). A prognostic score based on independent prognostic factors was defined. RESULTS: The median time to PSA progression on AA+P was 8.94 months. The median PFS on AA+D and AA+corticosteroids (P then D) was 10.35 and 20.07 months, respectively. A total of 56.25% of patients showed a decrease or stabilization in PSA levels after the switch. In univariate analysis, three markers of switch efficiency were significantly associated with a longer PFS: long hormone-sensitivity duration (≥5 years; median PFS 16.62 vs 4.17 months, hazard ratio [HR] 0.30, 90% confidence interval [CI] 0.16-0.56); low PSA level at the time of switch (<50 ng/mL; median PFS 15.21 vs 3.86 months, HR 0.33, 90% CI 0.18-0.60); and short time to PSA progression on AA+P (<6 months; median PFS 28.02 vs 6.65 months, HR 0.41 (90% CI 0.21-0.81). In multivariate analysis, hormone sensitivity duration and PSA level were independent prognostic factors. CONCLUSION: A steroid switch from P to D appears to be a safe and non-expensive way of obtaining long-term responses to AA in selected patients with mCRPC. A longer PFS has been observed in patients with previous long hormone sensitivity duration, and/or low PSA level and/or short time to PSA progression on AA+P.

Everolimus induced mood changes in breast cancer patients: a case-control study.

Introduction The PI3K/Akt/mTOR pathway plays a critical role in cancer cell growth, proliferation and angiogenesis, but also in brain homeostasis and the pathophysiology of mood disorders. The impact of the mTOR inhibitor everolimus on the mood of breast cancer patients is unknown. Materials and methods Consecutive, post-menopausal metastatic breast cancer patients receiving hormone therapy +/- everolimus were prospectively followed-up using the Beck Depression Inventory (BDI) and the MADRS (Montgomery and Asberg Depression Rating Scale) questionnaires. Results Post hoc tests comparing everolimus + hormonotherapy to hormonotherapy alone demonstrated a significant effect of everolimus after 6 weeks of treatment on BDI scores (t(1,38) = -2.0716, p < 0.05), and after 3 weeks (t(1,38) = -3.9165, p < 0.001) and 6 weeks of treatment (t(1,38) = -2.0373, p < 0.05) on MADRS scores. Analysis within each treatment group showed that the effect of time since treatment initiation on BDI and MADRS scores was specifically observed in the everolimus + hormonotherapy group (F(2,34) = 11.875, p < 0.001 and F(2,34) = 7.820, p < 0.01 respectively), but not in the hormonotherapy alone group (F(2,34) = 1.671, p > 0.2 and F(2,34) = 0.830, p > 0.2 respectively). Conclusions The mTOR inhibitor everolimus induces significant mood alterations in breast cancer patients. The evaluation of psychiatric symptoms is not only mandatory in the context of phase 1, dose-finding studies of PI3K/Akt/mTOR inhibitors, but is also clinically relevant in daily practice.

Pharmacokinetics and safety of DTS-108, a human oligopeptide bound to SN-38 with an esterase-sensitive cross-linker in patients with advanced malignancies: a Phase I study.

BACKGROUND: DTS-108 is a hydrosoluble prodrug, where the SN-38 moiety is covalently linked to a 20-amino acid vector peptide by a specific esterase-sensitive cross-linker, releasing 7-ethyl-10-hydroxycampthotecin (SN-38) by esterase bond cleavage. METHODS: The pharmacokinetics of DTS-108, adverse events graded according to NCI-CTCv3.1, dose-limiting toxicities at cycle 1, the maximum tolerated dose (MTD), and the recommended Phase II dose (RP2D) of intravenous DTS-108 (1-2 hours) every 2 weeks were evaluated in a first-in-human Phase I study in patients with advanced/metastatic carcinomas, according to an accelerated dose escalation design. SN-38 and SN-38 glucuronide (SN-38G) levels were evaluated with fluorescence high-performance liquid chromatography (HPLC) test, then liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods. RESULTS: Forty-two patients received DTS-108 across 14 dosing cohorts (range 3-416 mg/m2). At 416 mg/m2, three out of six patients had grade 4 neutropenia thereby defining the MTD and the RP2D at 313 mg/m2. Fluorescence HPLC was inaccurate to quantify DTS-108 and its metabolites (SN-38 and SN-38G). New processes and analytical LC/MS/MS methods for testing SN-38 were implemented. At a dose of 313 mg/m2, mean DTS-108, SN-38, and SN-38G area under the plasma concentration-time curve to infinity (coefficients of variation %) were 439,293 (24%), 1,992 (34%), and 4,538 (46%) h·ng/mL. Stable disease (according to Response Evaluation Criteria in Solid Tumors) was observed in nine patients. CONCLUSION: Assessing SN-38 concentration using fluorescence HPLC is questionable since this method failed to monitor dose escalation of DTS-108, a new topoisomerase I inhibitor, due to ex vivo degradation. LC/MS/MS methods were consistent in evaluating SN-38 exposures allowing drug monitoring. The maximum tolerated dose of DTS-108 was 416 mg/m2. The RP2D for intravenous DTS-108 was 313 mg/m2 every 2 weeks in patients with advanced/metastatic solid tumors.

Inaugural bone metastases in non-small cell lung cancer: a specific prognostic entity?

BACKGROUND: In non-small cell lung cancer patients (NSCLC), median survival from the time patients develop bone metastasis is classically described being inferior to 6 months. We investigated the subcategory of patients having an inaugural skeletal-related-event revealing NSCLC. The purpose of this study was to assess the impact of bone involvement on overall survival and to determine biological and tumoral prognosis factors on OS and PFS. An analysis of the subgroup of solitary bone metastasis patients was also performed. METHODS: In a population of 1208 lung cancer patients, 55 consecutive NSCLC patients revealed by inaugural bone metastasis and treated between 2003 and 2010, were retrospectively analysed. Survival was measured with a Kaplan-Meyer curve. Univariate and multivariate analysis were performed using the Stepwise Cox proportional hazard regression model. A p value of less than 0,05 was considered statistically significant. RESULTS: Estimated incidence of revealing bone metastasis is 4,5% among newly diagnosed lung cancer patients. Median duration of skeletal symptoms before diagnosis was 3 months and revealing bone site was located on axial skeleton in 70% of the cases. Histology was adenocarcinoma (78%), with small primary tumors Tx-T1-2 accounting for 71% of patients. Rate of second SRE is 37%.Median overall survival was 8.15 months, IQR [5-16 months], mean survival 13.4 months, and PFS was 3.5 months. In multivariate analysis, variables significantly associated with shortened survival were advanced T stage (HR=2.8; p=0.004), weight loss>10% (HR=3.1; p=0.02), inaugural spinal epidural metastasis (HR 2.5; p=0.0036), elevated C-reactive protein (HR=4.3; p=0.002) and TTF-1 status (HR=2.42; p=0.004). Inaugural spinal epidural metastasis is a very strong adverse pronostic factor in these cases, with a 3 months median survival. Single bone metastasis patients showed prolonged survival of 14.2 months versus 7.6 months, only in univariate analysis (HR=0.42; p=0.0059). CONCLUSION: Prognosis of lung cancer patients with inaugural SRE remains pejorative. Accurately estimating the survival of this population is helpful for bone surgical decision-making at diagnosis. The trend for a higher proportion of adenocarcinoma in NSCLC patients should result with an increasing number of patients with inaugural SRE at diagnosis.

Current, new and novel therapy for castration-resistant prostate cancer.

Androgen deprivation therapy is the standard of care for the initial treatment of metastatic prostate cancer. However, the majority of these patients live long enough to experience disease progression despite castration. This scenario is defined as castration-resistant prostate cancer (CRPC) and has a poor outcome and limited options for treatment. First-line treatment after hormonal therapy failure include secondary hormonal manipulation and docetaxel. Advances in the understanding of the molecular mechanisms underlying CRPC have translated into a recent increase in the number of effective systemic agents, and some of them have been already approved as first and second-line treatment. Despite these advances, the median survival in the first-line setting of metastatic CRPC is approximately 20 months and in the postdocetaxel setting is approximately 15 months. Promising and necessary new therapies in Phase III trials include hormonal agents, new cytotoxics agents, as well as other immunotherapeutics and antiprostate-specific membrane antigen therapies.

Cost effectiveness of integrated medicine in patients with cancer receiving anticancer chemotherapy.

PURPOSE: Ambulatory chemotherapy is patient friendly but may result in toxicity-induced unscheduled hospitalizations (TIUHs). This emerging issue may increase health care costs. We studied the cost effectiveness of a hospital-home monitoring program based on systematic iterative telephone calls after chemotherapy. PATIENTS AND METHODS: We retrospectively evaluated the rates of chemotherapy-induced unscheduled hospitalizations in patients who were treated in August 2008. Patients were contacted by telephone 1 day before chemotherapy and on the second and eighth days after undergoing chemotherapy. Costs associated with TIUHs were calculated and compared with those of a cohort concomitantly treated using the standard follow-up procedure. RESULTS: A total of 259 patients entered the hospital-home monitoring program. They were compared with 86 patients who had similar characteristics but underwent the standard treatment and follow-up procedure. Inclusion in the hospital-home monitoring program resulted in patients experiencing TIUHs approximately half as frequently as patients in the other group (2.4% v 4.9%; P < .01). Patients in the program experienced TIUHs for a median length of stay of 4 days, representing a nonsignificant reduction in duration of hospitalization (P not significant). Consequently, through a two-fold reduction in TIUH annual incidence, this program represents a reduction in unscheduled hospitalizations per year of 383 days, decreasing hospital costs by €201.468 ($292,468) per year. CONCLUSION: The hospital-home monitoring program is a cost-effective strategy for offering ambulatory chemotherapy treatment to patients with cancer. This program has become our standard procedure for ambulatory chemotherapy in patients with cancer.

Sorafenib-induced hepatocellular carcinoma cell death depends on reactive oxygen species production in vitro and in vivo.

Sorafenib is presently the only effective therapy in advanced hepatocellular carcinoma (HCC). Because most anticancer drugs act, at least in part, through the generation of reactive oxygen species, we investigated whether sorafenib can induce an oxidative stress. The effects of sorafenib on intracellular ROS production and cell death were assessed in vitro in human (HepG2) and murine (Hepa 1.6) HCC cell lines and human endothelial cells (HUVEC) as controls. In addition, 26 sera from HCC patients treated by sorafenib were analyzed for serum levels of advanced oxidation protein products (AOPP). Sorafenib significantly and dose-dependently enhanced in vitro ROS production by HCC cells. The SOD mimic MnTBAP decreased sorafenib-induced lysis of HepG2 cells by 20% and of Hepa 1.6 cells by 75% compared with HCC cells treated with 5 mg/L sorafenib alone. MnTBAP significantly enhanced by 25% tumor growth in mice treated by sorafenib. On the other hand, serum levels of AOPP were higher in HCC patients treated by sorafenib than in sera collected before treatment (P < 0.001). An increase in serum AOPP concentration ≥0.2 µmol/L chloramine T equivalent after 15 days of treatment is a predictive factor for sorafenib response with higher progression free survival (P < 0.05) and overall survival rates (P < 0.05). As a conclusion, sorafenib dose-dependently induces the generation of ROS in tumor cells in vitro and in vivo. The sera of Sorafenib-treated HCC patients contain increased AOPP levels that are correlated with the clinical effectiveness of sorafenib and can be used as a marker of effectiveness of the drug. .

Variability of sorafenib toxicity and exposure over time: a pharmacokinetic/pharmacodynamic analysis.

BACKGROUND: Sorafenib displays major interpatient pharmacokinetic variability. It is unknown whether the pharmacokinetics of sorafenib influence its toxicity. METHODS: We analyzed the severity and kinetics of sorafenib-induced toxicities in unselected consecutive patients with cancer, as well as their relationship with biological, clinical, and pharmacokinetic parameters. Toxicity was recorded bimonthly. Sorafenib plasma concentrations were assessed by liquid chromatography. RESULTS: For 83 patients (median age, 62 years; range, 21-84 years), median sorafenib 12-hour area under the curve (AUC(0-12)) was 52.8 mg · h/L (range: 11.8-199.6). A total of 51 patients (61%) experienced grade 3-4 toxicities, including hand-foot skin reactions (23%), asthenia (18%), and diarrhea (11%). Sorafenib AUC(0-12) preceding grade 3-4 toxicities was significantly higher than that observed in the remaining population (61.9 mg · h/L vs. 53 mg · h/L). In 25 patients treated with fixed doses of sorafenib for the first 4 months, median dose-normalized AUC(0-12) on day 120 was significantly lower than on day 15 (63 vs. 102 mg · h/L). The incidence of hypertension and hand-foot skin reactions significantly decreased over time. CONCLUSION: Sorafenib AUC(0-12) decreases over time, similarly to the incidence of hypertension and hand-foot skin reactions. Monitoring of sorafenib plasma concentrations may help to prevent acute severe toxicities and detect patients with suboptimal exposure at disease progression.

Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma.

BACKGROUND: Sorafenib induces frequent dose limiting toxicities (DLT) in patients with advanced hepatocellular carcinoma (HCC). Sarcopenia has been associated with poor performance status and shortened survival in cancer patients. PATIENTS AND METHODS: The characteristics of Child Pugh A cirrhotic patients with HCC receiving sorafenib in our institution were retrospectively analyzed. Sorafenib plasma concentrations were determined at each visit. Toxicities were recorded during the first month of treatment, and sarcopenia was determined from baseline CT-scans. RESULTS: Forty patients (30 males) were included. Eleven (27.5%) were sarcopenic. Eighteen patients (45%) experienced a DLT during the first month of treatment. Sarcopenic patients experienced significantly more DLTs than non-sarcopenic patients did (82% versus 31%, p = 0.005). Grade 3 diarrhea was significantly more frequent in sarcopenic patients than in non-sarcopenic patients (45.5% versus 6.9%, p = 0.01), but not grade 3 hand foot syndrome reaction (9% versus 17.2%, p = 1). On day 28, median sorafenib AUC (n = 17) was significantly higher in sarcopenic patients (102.4 mg/l.h versus 53.7 mg/l.h, p = 0.013). CONCLUSIONS: Among cirrhotic Child Pugh A patients with advanced HCC, sarcopenia predicts sorafenib exposure and the occurrence of DLT within the first month of treatment.

Feasibility of gemcitabine and oxaliplatin in patients with advanced biliary tract carcinoma and a performance status of 2.

The use of gemcitabine and oxaliplatin is well documented in selected patients with advanced biliary tract carcinoma (BTC), but little is known on the feasibility of systemic treatments in patients with a performance status (PS) of 2. We retrospectively examined the medical records of consecutive BTC patients with a PS of 2 receiving gemcitabine 1000 mg/m(2) plus oxaliplatin 100 mg/m(2) every 2 weeks from January 2003 to December 2011 in our institution. Body composition was analysed by computed tomography scan to detect sarcopenia. The primary evaluation criterion was safety. The secondary evaluation criteria were the response rate, progression-free survival (PFS) and overall survival (OS). Twenty-eight patients (median age: 63 years, range 41-83) received a total of 175 cycles (median per patient: 6, range 2-12). Ten patients (35.7%) had sarcopenia on the pretreatment computed tomography scan. The most frequent toxicities were thrombocytopenia (grades 2-4: n=4, 14.3%), peripheral neuropathy (grades 2-3: n=9, 32.1%) and cholangitis (n=4, 14.3%). The best response was a partial response in 10.7% of patients [95% confidence interval (CI): 0-22.2] and stable disease in 42.9% of patients. The median PFS and OS were 4.6 (95% CI: 2.5-6.3) and 7.5 (95% CI: 5.2-9.5) months, respectively. The median PFS and OS were significantly longer in patients without sarcopenia: 7.0 months (95% CI: 4.4-8.0) vs. 2.2 months (95% CI: 2.0-2.5), P less than 0.01, and 10.4 months (95% CI: 7.5-11.6) vs. 4.9 months (95% CI: 3.7-5.2), P less than 0.01, respectively. In our experience, gemcitabine-oxaliplatin was feasible and induced effective palliation in PS2 patients with advanced BTC. Further studies are warranted to confirm these findings.

Interaction between serotonin reuptake inhibitors, 5-HT3 antagonists, and NK1 antagonists in cancer patients receiving highly emetogenic chemotherapy: a case-control study.

BACKGROUND: Previous reports suggested that selective serotonin reuptake inhibitors (SSRI) could decrease the activity of 5-hydroxytryptamine type 3 (5-HT3) antagonists against acute chemotherapy-induced nausea and vomiting (CINV), possibly through serotonin accumulation for 5-HT3 receptors. PATIENTS AND METHODS: Chemonaive cancer patients receiving SSRI and antiemetic agents, including the 5-HT3 antagonist ondansetron and the neurokinin 1 (NK1) antagonist aprepitant for highly emetogenic chemotherapy (etoposide-platinum), were matched to control patients for the following variables: age, gender, primary tumor, past history of gestational emesis, chronic intake of benzodiazepines and/or corticosteroids, chronic alcohol intake, and aprepitant use. The primary evaluation criterion was the occurrence of acute vomiting during the first two cycles of treatment. RESULTS: Forty-four patients were eligible for this analysis. The proportion of patients, who experienced at least one episode of grade ≥ 1 acute vomiting in patients receiving SSRI, compared to patients who did not, was significantly higher (59.1 vs. 22.7%, respectively, p = 0.03, odds ratio 4.72, 95% confidence interval 1.13-22.88). Grade ≥ 2 acute vomiting was also significantly more frequent in patients receiving SSRI, even after the implementation of aprepitant to antiemetic prophylaxis (41.2 vs. 5.9%, p = 0.04). CONCLUSIONS: Our findings reinforce the hypothesis that SSRI decrease the antiemetic activity of the 5-HT3 serotonin antagonist ondansetron, resulting in higher rates of acute vomiting in cancer patients despite adequate antiemetic prophylaxis. Adding the NK1 antagonist aprepitant do not counterbalance the deleterious effect of SSRI, probably due to the synergistic effects of SSRI and NK1 antagonists on serotonin transmission.

[Management of metastatic castration-resistant prostate cancer following docetaxel]. / Prise en charge des cancers de prostate résistants à la castration métastatiques après échec du docétaxel.

Abiraterone acetate and cabazitaxel have shown an overall survival benefit in patients with metastatic castration-resistant prostate cancer following docetaxel failure. Both have been approved in this indication. The search, follow-up and characterisation of circulating tumor cells should help for the response evaluation and the choice between the two treatments. Recently, alpharadin (radium-223 chloride) has demonstrated also an overall survival advantage in a large phase III trial. Other hormone therapies as MDV3100 or TAK700 are very promising. In undifferentiated cancers with neuroendocrine features, etoposide and platinum salts combinations have shown low efficiency.

Gemcitabine and oxaliplatin as second-line treatment in patients with hepatocellular carcinoma pre-treated with sorafenib.

Some patients with advanced hepatocellular carcinoma (HCC) progressing under sorafenib remain eligible for further systemic therapy. Little is known on the feasibility of systemic treatment beyond sorafenib in this setting. Consecutive HCC patients pre-treated with sorafenib received gemcitabine 1,000 mg/m² and oxaliplatin 100 mg/m² every 14 days. Exclusion criteria included Child C cirrhosis, PS≥3, creatinine clearance<20 ml/min, albumin<25 g/L and bilirubin>54 µmol/L. Pre-treatment body composition was evaluated by CT scan to detect muscle wasting (sarcopenia). The primary evaluation criterion was safety. Secondary evaluation criteria were response rate, and progression-free (PFS) and overall survival (OS). Eighteen patients (median age: 64 years, range 25-77) received a total of 90 cycles (median per patient: 4, range 1-16). Eight patients (44.4 %) had a PS of 2, 5 (27.8%) had Child-Pugh B cirrhosis and 13 (72.2%) had a CLIP score>3. The most frequent toxicities were thrombocytopenia (grade 2-4: n=7, 38.9%) and peripheral neuropathy (grade 2-3: n=7, 38.9%). The overall response rate was 18.8% (95% CI: 0-37.9), and another 18.8 % of patients had stable disease. The median PFS and OS were 3.2 (95% CI: 2.3-3.9) and 4.7 (95% CI: 3.8-8.1) months, respectively. Overall survival was significantly longer in patients without sarcopenia [10.0 months (95% CI: 7.0-13.8) vs. 3.0 months (95 % CI: 2.5-3.9), p<0.001] and in patients with an ECOG PS<2 [8.1 months (95% CI: 7.0-13.8) vs. 3.8 months (95% CI: 2.5-3.9), p=0.017]. In our experience, gemcitabine-oxaliplatin was feasible and had detectable clinical activity in HCC patients pre-treated with sorafenib. Further studies are needed to confirm these findings.