Les auteurs évaluent l'apport d'une chronothérapie comportant du 5-fluoro-uracile (5-FU), de l'acide folinique et du carboplatine (en infusion ambulatoire par pompe chronomodulable 5/21 jours) au ...traitement de patients souffrant d'un cancer de l'œsophage (52 cas) ou de l'estomac (56 cas) essentiellement de stade avancé. La tolérance au traitement fut très favorable (grades 3–4, pourcentage de patients
: mucite 11–23
%
; leucocytes 6–19
%
; plaquettes 18–50
%
; pas de troubles digestifs ni d'alopécie). L'évolution tumorale fut aussi intéressante avec des taux de réponses majeures de 61
% (estomacs métastatiques) à 79
% (œsophages). La survie modeste dans les cancers de l'œsophage (médiane
: 9,2 mois) fut plus favorable dans les cancers de l'estomac (médiane dans les cas disséminés
: 12,7 mois
; 72
% survivants à cinq ans dans les cas traités après chirurgie curative).
The authors evaluated the impact of a chronotherapy with 5-FU, folinic acid and carboplatine (chronomodulated infusions by ambulatory pumps; 5/21 days) for the management of oesophagus (52 cases) and gastric (56 cases) cancer patients. The overall tolerance of treatment was gauged excellent (grade 3–4; % patients: mucitis: 11–23%; leucopenia 6–19%
; thrombopenia 18–50%; almost no digestive disturbances nor alopecia). Also tumor outcome was considered interesting with major responses rate in 61% (gastric) to 79% (oesophagus) of patients. The median survival of oesophageal cancer was limited to 9.2 months; the one of disseminated gastric cancer was 12.7 months but 72% of curatively resected patients were alive at 5
+
years.
Abstract
Background
Human papillomavirus (HPV) vaccination programs achieve substantial population-level impact, with effects extending beyond protection of vaccinated individuals. We assessed trends ...in HPV prevalence up to 8 years postvaccination among men and women in the Netherlands, where bivalent HPV vaccination, targeting HPV types 16/18, has been offered to (pre)adolescent girls since 2009 with moderate vaccination coverage.
Methods
We used data from the PASSYON study, a survey initiated in 2009 (prevaccination) and repeated biennially among 16- to 24-year-old visitors of sexual health centers. We studied genital HPV positivity from 2009 to 2017 among women, heterosexual men, and unvaccinated women using Poisson generalized estimating equation models, adjusted for individual- and population-level confounders. Trends were studied for 25 HPV types detected by the SPF10-LiPA25 platform.
Results
A total of 6354 women (64.7% self-reported unvaccinated) and 2414 heterosexual men were included. Percentual declines in vaccine types HPV-16/18 were observed for all women (12.6% per year 95% confidence interval {CI}, 10.6–14.5), heterosexual men (13.0% per year 95% CI, 8.3–17.5), and unvaccinated women (5.4% per year 95% CI, 2.9–7.8). We observed significant declines in HPV-31 (all women and heterosexual men), HPV-45 (all women), and in all high-risk HPV types pooled (all women and heterosexual men). Significant increases were observed for HPV-56 (all women) and HPV-52 (unvaccinated women).
Conclusions
Our results provide evidence for first-order herd effects among heterosexual men against HPV-16/18 and cross-protective types. Additionally, we show second-order herd effects against vaccine types among unvaccinated women. These results are promising regarding population-level and clinical impact of girls-only bivalent HPV vaccination in a country with moderate vaccine uptake.
This study presents trends in human papillomavirus (HPV) positivity since girls-only HPV vaccine introduction in the Netherlands, with moderate vaccine uptake. We show declining prevalences of vaccine types HPV-16/18 in heterosexual men and unvaccinated women, and of cross-protective types in heterosexual men.
Cent dix patients consécutifs porteurs d’un cancer colorectal ont bénéficié d’une chronothérapie de 48heures administrée toutes les deux semaines, et comportant du 5-fluorouracil (5 FU) 3g/m2, de ...l’acide folinique (600mg/m2, forme lévogyre ou 1200mg/m2 – forme racémique) et de l’oxaliplatine (85mg/m2 en situation adjuvante ou 100mg/m2 en situation palliative). Les composés étaient administrés sur un mode chronomodulé, soit le 5 FU et l’acide folinique en infusion de 22h à 10h avec un pic à 4h, l’oxaliplatine de 10h à 22h avec un pic à 16h. La tolérance a été excellente, avec un maximum de 17 % des patients présentant une toxicité de grade 3. La toxicité fut plus importante chez les femmes, les sujets âgés (>=à 70ans) et en cas de délivrance à débit constant. En situation adjuvante (60 patients), les survies sans progression et globale ont été observées respectivement à 76 % à 42+mois et 88 % à 45+mois. Parmi les 50 patients métastatiques, 52 % ont répondu de façon significative à la chimiothérapie avec un contrôle global de la maladie chez 68 %. Trente pour cent des patients ont pu bénéficier également d’une chirurgie à visée curative après la chimiothérapie d’induction. La survie médiane sans progression fut de sept mois, mais la survie médiane globale n’était pas atteinte à 31+mois. Les sujets âgés ont eu une survie moins favorable. En conclusion, vu l’excellent index thérapeutique observé, nous proposons notre traitement chrono-FOLFOX 2-12 comme traitement standard chez les patients souffrant d’un cancer colorectal.
One hundred and ten consecutive patients suffering from a colorectal cancer received chronotherapy infused over two days every two weeks. Each course comported 5 FU 3g/m2, folinic acid (600mg/m2 – l. form or 1200mg/m2 – racemic form) and oxaliplatin (85/mg/m2 – adjuvant indication or 100mg/m2 – palliative indication). According to chronobiological concepts, 5 FU and folinic acid were infused from 10 pm to 10 am with a peak at 4 am while oxaliplatin was delivered from 10 am to 10 pm with a peak at 4 pm. The overall tolerance was excellent with a maximum of 17% patients experiencing a grade 3 toxicity. The toxicity was higher in women, in older patients (>=70) or in case of flat infusion. In adjuvant situation (60 cases), progression free and overall survivals established respectively at 76% (42+months) and 88% (45+months). Fifty-two percent response rate were recorded within the palliative group (50 cases) with an overall 68% disease control. Median progression free survival was seven months but median survival was not attained at 31+ months. Thirty percent patients could benefit from a curative surgery after chemotherapy. Older patients (>=70) experienced worsened survival. In conclusion, we think that our chrono-FOLFOX 2-12 should be proposed as standard treatment for colorectal cancer patients.
Data on the impact of human papillomavirus (HPV) vaccination on the population HPV prevalence are largely obtained from women. We assessed the impact of the girls‐only HPV16/18 vaccination program in ...the Netherlands that started in 2009, on trends in HPV prevalence among women and heterosexual men, using data from the PASSYON study. In this cross‐sectional study, the HPV prevalence among 16‐ to 24‐year‐old visitors to sexually transmitted infection clinics was assessed in 2009, 2011, 2013, and 2015. We compared the genital postvaccination HPV prevalence with the prevaccination prevalence (2009) using Poisson GEE models. In total, we included 4,996 women and 1,901 heterosexual men. The percentage of women who reported to be vaccinated increased from 2.3% in 2009 to 37% in 2015. Among all women, the HPV16/18 prevalence decreased from 23% prevaccination to 15% in 2015 (adjusted prevalence ratio aPR 0.62, ptrend < 0.01). Among heterosexual men, the HPV16/18 prevalence decreased from 17% prevaccination to 11% in 2015 (aPR 0.52, ptrend < 0.01). Of the heterosexual men with a steady partner, HPV16/18 prevalence was lower among those whose steady partner had been vaccine‐eligible in the national immunization program (aPR 0.13). Among unvaccinated women, the HPV16/18 prevalence in 2015 was not different from prevaccination. The decreasing HPV16/18 prevalence among heterosexual men and the reduced HPV16/18 prevalence among heterosexual men with a vaccine‐eligible steady partner strongly suggests herd protection from girls‐only vaccination. Absence of notable herd effects among unvaccinated women 6 years postvaccination may be due to the moderate vaccine uptake among girls in the Netherlands.
What's new?
Human papillomavirus (HPV) is a sexually transmitted virus that plays a causal role in the development of anogenital and oropharyngeal cancers in both men and women. The population‐level impact of HPV vaccination programs on the HPV prevalence has however mainly been studied in women. This study shows decreasing trends in the HPV16 and HPV18 prevalence among both women and heterosexual men after the introduction of a girls‐only HPV16/18 vaccination program in the Netherlands. The findings provide compelling evidence for herd protection in men. Because HPV16/18 are the most oncogenic types, HPV‐related cancers are expected to decline in both sexes after girls‐only HPV vaccination.
Abstract
Background: Trastuzumab (Herceptin®; H) is a standard component of adjuvant treatment in patients with HER2+ early breast cancer (eBC) and is supported by all major treatment guidelines. The ...efficacy and safety of Herceptin intravenous (H IV) and Herceptin subcutaneous (H SC) have been shown to be comparable. The main advantage of SC administration is its shorter administration time. Administration at home for selected patients will allow greater independence and may lead to an improved quality of life. In this study, we assessed the safety and tolerability of H SC administered at home by a healthcare professional (HCP) in patients with HER2+ eBC.
Methods: Patients with HER2+ eBC who previously completed 6 cycles of H IV could be included in the study to receive 12 additional cycles of H for a total of 18 cycles. The 12 additional 3-week cycles consisted of 3 cycles of H IV in the hospital (6 mg/kg; cycles 7 to 9; period 1); 3 cycles of H SC in the hospital (600 mg; cycles 10 to 12; period 2); and 6 cycles of H SC administered in the home by a HCP (600 mg; cycles 13 to 18; period 3). Patients are being followed for a total of 24 months after their last treatment. Safety is being assessed from the adverse events (AEs) reported during the study. Patient-reported outcomes were obtained from validated questionnaires for: the satisfaction and quality of the treatments and care, and for symptom severity (0 absent to 10 worst). HCPs also reported on their experiences with both treatments.
Results: A total of 102 patients were treated in the study between November 2013 and July 2015 and will be followed for safety and efficacy through July 2017. The primary analysis reported here was done after the last 4-week post-treatment follow-up was completed (September 2015). Patient mean age at baseline was 54.4±12.3 (SD) years. A total of 91 (89%) patients reported 549 AEs: 535 (97%) of these were grade 1 or 2 and 194 (35%) were considered treatment related. The proportions of patients with at least one related AE were 7% for H IV period 1, 32% for H SC period 2, and 47% for H SC period 3, which was twice as long as periods 1 or 2. A total of 8 serious AEs were reported in 8 patients (2 each in periods 1 and 2; 4 in period 3). Prior to the first at-home SC administration (cycle 13), 99% of patients were satisfied to a large or very large extent with the IV and SC treatments at the hospital. At cycle 17, 100% of patients were satisfied to a large or very large extent with the SC treatment at home, and 100% of patients thought treatment at home was beneficial to a large or very large extent. In all 3 treatment periods, maximum mean scores were 3.0−3.8 for the most severe symptoms (fatigue, disturbed sleep, and numbness or tingling). All HCPs considered both administration routes to be fairly easy or very easy, and SC administration to be quicker and require fewer preparation resources.
Conclusions: The safety analyses and patient-reported outcomes recorded in this study indicate that H SC administered by a HCP at home instead of at the hospital was not associated with any new safety signals and was considered beneficial by the patients and HCPs.
Citation Format: Cocquyt VF, Martinez-Mena CL, Martens MT, D'Hondt RG, Graas M-PL, Evron E, Fried G, Ben-Baruch NE, Dijkstra AC, Van De Walle EI. BELIS: Safety and tolerability of at home administration of trastuzumab (Herceptin®) subcutaneous for the treatment of patients with HER2-positive early breast cancer abstract. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-17.
Summary Objectives Data from a vaccine trial and from post-vaccine surveillance in the United Kingdom have suggested that the bivalent HPV-16/18 vaccine offers cross-protection against HPV-6/11 and ...protection against anogenital warts (AGW). We studied the effect of the bivalent vaccine on genital HPV-6/11 positivity and AGW in the Netherlands. Methods We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional study among 16- to 24-year-old sexually transmitted infection (STI) clinic attendants. Vaginal self-swabs were analyzed for type specific HPV and AGW were diagnosed at the STI-clinic. Prevalence of HPV-6 and/or HPV-11 and AGW were compared between self-reported vaccinated and unvaccinated women by log-binomial regression analysis, adjusted for demographics and risk behavior. Results Of the 1198 women included, 56% reported to be vaccinated at least once. Relative to unvaccinated women, the adjusted prevalence ratio (PR) for HPV-6/11 was 1.03 (95% confidence interval CI 0.74–1.43) for women vaccinated at least once. The crude PR for AGW was 0.67 (95% CI 0.22–2.07) for women vaccinated at least once. Adjustment did not change these results. Conclusions We observed no cross-protective effect of the bivalent vaccine on genital HPV-6/11 positivity and a non-significant partially protective effect on AGW.
In a previous study of a t(4;16)(q26;p13) translocatlon, found in a human malignant T-cell lymphoma the BCMA gene, located on chromosome band 16p13.1, has been characterized. In this study we show ...that the BCMA gene is organized into three exons and its major initiation transcription site is located 69 nucleotldes downstream of a TATA box. RNase protection assays demonstrated that the BCMA gene is preferentially expressed in mature B cells, suggesting a role for this gene in the B-cell developmental process. A cDNA complementary to the BCMA cDNA was cloned and sequenced and its presence was assessed by RNase protection assay and anchor-PCR amplification. This antlsense-BCMA RNA is transcribed from the same locus as BCMA, and exhibits mRNA characteristic features, e.g. polyadenylation and splicing. It also contains an ORF encoding a putative 115 aa polypeptlde, presenting no homology with already known sequences. RNase protection assays demonstrated the simultaneous expression of natural sense and antisense-BCMA transcripts In the majority of human B-cell lines tested.
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