Background: Sorafenib is the first-line treatment for advanced hepatocellular carcinoma (HCC). The management of its side effects is improving. This study aimed to assess, in real life, if this ...translates into a better prognosis. Methods: This was a retrospective study of advanced HCC patients treated with sorafenib between 2007 and 2017. Results: 188 advanced HCC patients received > 4 weeks of sorafenib. Median treatment duration was 5.4 months and median overall survival (mOS) 10 months (95% confidence interval 15–27). Sorafenib was initiated in 65 patients in 2007–2012 and 123 in 2013–2017. Both groups were comparable except for Barcelona Clinic liver cancer class. Tumor progression, disease control (DC) rate, and incidence of toxicity were similar in the 2 periods, but the duration of treatment (4.3 vs. 5.9 months; p < 0.01) and mOS (8 vs. 12 months; p < 0.002) differed. Among progressive disease patients, mOS was similar (7 months) but for those who had DC at 8 weeks, mOS was longer in the recent period (13 vs. 27 months; p < 0.0001). In the univariate analysis of OS, the period of treatment had a prognostic value. Conclusion: When comparing 2 periods of treatment in advanced HCC patients under sorafenib, duration of treatment and mOS were higher in the recent period. While mOS did not differ for patients who progressed, it was 2-fold higher in the recent period for those who had tumor control. Improvements in the use of sorafenib seem to be associated with better outcomes limited to patients with DC.
The fast spread of COVID-19 is related to the highly infectious nature of SARS-CoV-2. The disease is suggested to be transmitted through saliva droplets and nasal discharge. The saliva quantification ...of SARS-CoV-2 in real-time PCR from asymptomatic or mild COVID-19 adults has not been fully documented. This study analyzed the relationship between salivary viral load on demographics and clinical characteristics including symptoms, co-morbidities in 160 adults diagnosed as COVID-19 positive patients recruited between September and December 2020 in four French centers. Median initial viral load was 4.12 log
copies/mL (IQR 2.95-5.16; range 0-10.19 log
copies/mL). 68.6% of adults had no viral load detected. A median load reduction of 23% was observed between 0-2 days and 3-5 days, and of 11% between 3-5 days and 6-9 days for the delay from onset of symptoms to saliva sampling. No significant median difference between no-symptoms vs. symptoms patients was observed. Charge was consistently similar for the majority of the clinical symptoms excepted for headache with a median load value of 3.78 log
copies/mL 1.95-4.58 (
< 0.003). SARS-CoV-2 RNA viral load was associated with headache and gastro-intestinal symptoms. The study found no statistically significant difference in viral loads between age groups, sex, or presence de co-morbidity. Our data suggest that oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.
To determine if commercially available mouthwash with β-cyclodextrin and citrox (bioflavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral ...load.
In this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive patients aged 18–85 years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8 days were recruited. A total of 176 eligible patients were randomly assigned (1:1) to CDCM or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6 days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2.
The intention-to-treat analysis demonstrated that, over the course of 1 day, CDCM was significantly more effective than placebo 4 hours after the first dose (p 0.036), with a median percentage (log10 copies/mL) decrease T1–T2 of –12.58% (IQR –29.55% to –0.16%). The second dose maintained the low median value for the CDCM (3.08 log10 copies/mL; IQR 0–4.19), compared with placebo (3.31 log10 copies/mL; IQR 1.18–4.75). At day 7, there was still a greater median percentage (log10 copies/mL) decrease in salivary viral load over time in the CDCM group (–58.62%; IQR –100% to –34.36%) compared with the placebo group (–50.62%; IQR –100% to –27.66%). These results were confirmed by the per-protocol analysis.
This trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva.
The aim of this study was to determine whether self-collected pure saliva (SCPS) is comparable to nasopharyngeal (NP) swabs in the quantitative detection of SARS-CoV-2 by RT-PCR in asymptomatic, mild ...patients with confirmed COVID-19. Thirty-one patients aged from 18 to 85 years were included between 9 June and 11 December 2020. A SCPS sample and a NP sample were taken for each patient. Quantitative PCR was performed to detect SARS-CoV-2 viral load. Results of SCPS vs. NP samples testing were compared. Statistical analyses were performed. Viral load was significantly correlated (r = 0.72). The concordance probability was estimated at 73.3%. In symptomatic adults, SCPS performance was similar to that of NP swabs (Percent Agreement = 74.1%; p = 0.11). Thus, the salivary test based on pure oral saliva samples easily obtained by noninvasive techniques has a fair agreement with the nasopharyngeal one in asymptomatic, mild patients with a confirmed diagnosis of COVID-19.
Whether triplet chemotherapy is superior to doublet chemotherapy in advanced biliary tract cancer (BTC) is unknown.
In this open-label, randomized phase II-III study, patients with locally advanced ...or metastatic BTC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive oxaliplatin, irinotecan, and infusional fluorouracil (mFOLFIRINOX), or cisplatin and gemcitabine (CISGEM) for a maximum of 6 months. We report the results of the phase II part, where the primary end point was the 6-month progression-free survival (PFS) rate among the patients who received at least one dose of treatment (modified intention-to-treat population) according to Response Evaluation Criteria in Solid Tumors version 1.1 (statistical assumptions: 6-month PFS rate ≥ 59%, 73% expected).
A total of 191 patients (modified intention-to-treat population, 185: mFOLFIRINOX, 92; CISGEM, 93) were randomly assigned in 43 French centers. After a median follow-up of 21 months, the 6-month PFS rate was 44.6% (90% CI, 35.7 to 53.7) in the mFOLFIRINOX arm and 47.3% (90% CI, 38.4 to 56.3) in the CISGEM arm. Median PFS was 6.2 months (95% CI, 5.5 to 7.8) in the mFOLFIRINOX arm and 7.4 months (95% CI, 5.6 to 8.7) in the CISGEM arm. Median overall survival was 11.7 months (95% CI, 9.5 to 14.2) in the mFOLFIRINOX arm and 13.8 months (95% CI, 10.9 to 16.1) in the CISGEM arm. Adverse events ≥ grade 3 occurred in 72.8% of patients in the mFOLFIRINOX arm and 72.0% of patients in the CISGEM arm (toxic deaths: mFOLFIRINOX arm, two; CISGEM arm, one).
mFOLFIRINOX triplet chemotherapy did not meet the primary study end point. CISGEM doublet chemotherapy remains the first-line standard in advanced BTC.
Small bowel adenocarcinoma (SBA) is a rare tumour. We conducted a prospective cohort to describe the prevalence, survival and prognostic factors in unselected SBA patients. The study enrolled ...patients with all stages of newly diagnosed or recurrent SBA at 74 French centres between January 2009 and December 2012. In total, 347 patients were analysed; the median age was 63 years (range 23–90). The primary tumour was in the duodenum (60.6%), jejunum (20.7%) and ileum (18.7%). The prevalence of predisposing disease was 8.7%, 6.9%, 1.7%, 1.7% and 0.6% for Crohn disease, Lynch syndrome, familial adenomatous polyposis, celiac disease and Peutz‐Jeghers syndrome, respectively. At diagnosis, 58.9%, 5.5% and 35.6% of patients had localised and resectable, locally advanced unresectable and metastatic disease, respectively. Crohn disease was significantly associated with younger age, poor differentiation and ileum location, whereas Lynch syndrome with younger age, poor differentiation, early stage and duodenum location. Adjuvant chemotherapy (oxaliplatin‐based in 89.9%) was performed in 61.5% of patients with locally resected tumours. With a 54‐months median follow‐up, the 5‐year overall survival (OS) was 87.9%, 78.2% and 55.5% in Stages I, II and III, respectively. The median OS of patients with Stage IV was 12.7 months. In patients with resected tumours, poor differentiation (p = 0.047) and T4 stage (p = 0.001) were associated with a higher risk of death. In conclusion, our study showed that the prognosis of advanced SBA remains poor. Tumour characteristics differed according to predisposing disease. In SBA‐resected tumours, the prognostic factors for OS were grade and T stage.
What's new?
Small bowel adenocarcinoma is a rare disease but incidences are increasing in Europe and the US because of increases in duodenal cancers. This study from France found that Crohn's disease and Lynch syndrome, a genetic condition associated with colorectal cancers, combined with younger age and poor differentiation predisposed for the disease. The authors also linked poor differentiation and advanced tumor staging with short overall survival in patients with locally resected tumors, underscoring that the prognosis for advanced adenocarcinomas remains poor.
GEMPAX was an open-label, randomized phase III clinical trial designed to assess the efficacy and tolerability of gemcitabine plus paclitaxel versus gemcitabine alone as second-line treatment for ...patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who previously received 5-fluorouracil, oxaliplatin, and irinotecan.
Patients with histologically or cytologically confirmed mPDAC were randomly assigned (2:1) to receive GEMPAX (paclitaxel 80 mg/m
+ gemcitabine 1,000 mg/m
; IV; once at day (D) 1, D8, and D15/arm A) or gemcitabine (arm B) alone once at D1, D8, and D15 every 28 days until progression, toxicity, or patient's decision. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), quality of life, and safety.
Overall, 211 patients (median age, 64 30-86 years; 62% male) were included. After a median study follow-up for alive patients of 13.4 versus 13.8 months in arm A versus arm B, the median OS (95% CI) was 6.4 (5.2 to 7.4) versus 5.9 months (4.6 to 6.9; hazard ratio HR, 0.87 0.63 to 1.20;
= 0.4095), the median PFS was 3.1 (2.2 to 4.3) versus 2.0 months (1.9 to 2.3; HR, 0.64 0.47 to 0.89;
= 0.0067), and the ORR was 17.1% (11.3 to 24.4) versus 4.2% (0.9 to 11.9;
= 0.008) in arm A versus arm B, respectively. Overall, 16.7% of patients in arm A and 2.9% in arm B discontinued their treatment because of adverse events (AEs). One grade 5 AE associated with both gemcitabine and paclitaxel was reported in arm A (acute respiratory distress), and 58.0% versus 27.1% of patients experienced grade ≥3 treatment-related AEs in arm A versus arm B, among which 15.2% versus 4.3% had anemia, 15.9% versus 15.7% had neutropenia, 19.6% versus 4.3% had thrombocytopenia, 10.1% versus 2.9% had asthenia and 12.3% versus 0.0% had neuropathy.
While GEMPAX did not meet the primary end point of OS versus gemcitabine alone in patients with mPDAC in the second-line setting, both PFS and ORR were significantly improved.
Abstract 4002
In lower-risk MDS, anemia is the main therapeutic challenge. ESAs can frequently correct anemia, but not all pts respond and median response duration to ESAs is only about 2 years. LEN ...yields RBC transfusion-independence (TI) in 65% of lower risk MDS with del(5q) and about 25% of lower risk MDS without del 5q (Raza A, et al, Blood, 2008, 111, 1). However, in the last study, pretreatment with ESAs was not always documented, and the efficacy of LEN on anemia of non-del(5q) MDS refractory to ESAs remains unknown.
31 consecutive lower-risk non-del(5q) MDS with anemia refractory to ESAs were treated with LEN through a compassionate program. Pts wn@ere from 7 centers of the Groupe Francophone des Myélodysplasies. They had previously received an ESA during at least 12 weeks, including epoetin alfa (80,000 U qw, n= 17), epoetin beta (60,000 qw, n=3), darbepoetin (500 μg q2 w, n=11), and GCSF was added in 20 patients.
At inclusion in the program, median age was 69 (range 41–87), including RA (n=3), RAEB-1 (n=2), RARS (n=11), RCMD (n=12), and RCMD-RS (n=3). Karyotype was fav (n=27), int (n=2), and unfav (n=2). IPSS was low (n=15), int-1 (n=16). Median ESAs treatment duration was 3 months (3-36+). According to IWG 2006 criteria, 18 pts were primary resistant to ESAs while 13 relapsed after a 12 months median duration of erythroid response (range 3–36). At onset of LEN, median Hb level was 8.9 g/dl (range 6.3–9.9), median endogenous EPO level 172 UI/l (48-1092 UI/l). The starting doses of LEN were 5 (n=10) or 10 mg (n=21), daily (n=26) or daily × 3 wks q28d cycle (n=5). 20 pts also received ESAs including EPO alone (n=6) and EPO+GCSF (n=14). Deep vein thrombosis (DVT) prophylaxis was made in 22 pts (71%) with aspirin (n=20), heparin (n=1) or warfarin (n=1). With a median follow-up of 16 months (range 3–27), 13 (42%) pts obtained an erythroid response (IWG 2006 criteria). All responses occurred within the first 3 months of treatment. 4 of the responders (31%) relapsed at 4, 9, 15, and 16 months whereas 9 (69%) were still responding after 3+ to 24+ months. Median response duration was 12 months. Of the 24 RBC-TD patients, 10 (42 %) achieved RBC-TI of 12 months median duration (range 3+-22+). The most common drug-related grade 3/4 adverse events were neutropenia (n=6, 19%) and thrombocytopenia (n=6, 19%). No pt developed DVT. One pt with RCMD and complex karyotype developed AML and died at 3.1 months from treatment onset, 2 additional pts who resisted to LEN died 5 and 6 months after LEN interruption. According to IWG 2006 criteria, the proportion of erythroid responses was significantly lower in the 8 patients who had developed neutropenia or thrombocytopenia: 1/8 vs 12/23, p = 0.038. Among the 24 RBC-TD patients, the proportion of RBC-TI was significantly lower in the 8 patients who had developed neutropenia or thrombocytopenia: 1/8 vs 9/16, p = 0.05. Median RBC-TI duration was significantly lower in the 8 patients who had developed neutropenia or thrombocytopenia: 0 vs 9 months, p=0.05. Other factors such as age, sex, WHO classification, time between diagnosis and treatment, response to ESAs, interval between ESAs and REV, WBC count, hemoglobin level, platelet count, LEN dose, combination to ESAs, did not significantly influence response to LEN, and RBC-TI duration.
In this cohort of lower-risk non-del(5q) MDS refractory to ESAs LEN yielded RBC transfusion independence in more than 40% of the pts and was well-tolerated. Treatment-induced cytopenia was associated with fewer erythroid responses and shorter response duration.
No relevant conflicts of interest to declare.
Epidermal growth factor receptor (EGFR) and hepatocyte growth factor (HGF)/mesenchymal–epithelial transition (MET) pathways, which promote tumour growth and proliferation, are often deregulated in ...advanced gastroesophageal adenocarcinomas. We assessed whether adding panitumumab (an EGFR inhibitor) or rilotumumab (a HGF inhibitor) to first-line fluoropyrimidine-based and platinum-based chemotherapy (modified oxaliplatin, leucovorin and fluorouracil mFOLFOX6) benefits to patients with advanced gastroesophageal adenocarcinoma.
This phase II, open-label, randomised, three-arm study enrolled patients ≥18 years, with advanced gastroesophageal adenocarcinoma, Eastern Cooperative Oncology Group performance status 0–1 and no known HER2 overexpression. Patients were randomly assigned (1:1:1) mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h) alone or combined with panitumumab (6 mg/kg) or rilotumumab (10 mg/kg) every 2 weeks until limiting toxicity, patient's refusal or disease progression. The primary end-point was the 4-month progression-free survival (PFS) rate. Secondary end-points included overall survival (OS) and tolerance.
The study enrolled 162 patients in 29 French centres. The median follow-up was 23.6 months (interquartile range = 16.4–29.0). The 4-month PFS rate was 71% (95% confidence interval CI = 57–82) with chemotherapy alone, 57% (95% CI = 42–71) combined with panitumumab and 61% (95% CI = 47–74) combined with rilotumumab. Median OS was 13.1 months (95% CI = 8.7–16.9) with chemotherapy alone, 8.3 months (95% CI = 6.2–13.2) combined with panitumumab and 11.5 months (95% CI = 7.9–17.1) combined with rilotumumab. Adverse events grade ≥III occurred less frequently with chemotherapy alone (62%) than with panitumumab (83%) and rilotumumab (89%).
We found no benefit in adding panitumumab or rilotumumab to mFOLFOX6 first-line chemotherapy to treat advanced gastroesophageal adenocarcinoma patients.
European Clinical Trials Database, number 2009-012797-12.
•Fluoropyrimidine-platinum doublets are the standard for advanced gastric cancer.•EGFR and HGF/MET pathways are often deregulated in advanced gastric cancer.•Panitumumab and rilotumumab are directed against EGFR and HGF, respectively.•Adding panitumumab to chemotherapy is ineffective in advanced gastric cancer.•Adding rilotumumab to chemotherapy is ineffective in advanced gastric cancer.
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