One-year COVID-19 outcomes on the oncology care patient pathway: Results of a French descriptive, cross-sectional comprehensive study (ONCOCARE-COV).

BACKGROUND: The COVID-19 pandemic led to a widely documented disruption in cancer care pathway. Since a resurgence of the pandemic was expected after the first lockdown in France, the global impact on the cancer care pathway over the year 2020 was investigated. AIMS: This study aimed to describe the changes in the oncology care pathway for cancer screening, diagnosis, assessment, diagnosis annoucement procedure and treatment over a one-year period. MATERIALS & METHODS: The ONCOCARE-COV study was a comprehensive, retrospective, descriptive, and cross-sectional study comparing the years 2019 and 2020. All key indicators along the cancer care pathway assessing the oncological activity over four periods were described. This study was set in a high-volume, public, single tertiary care center divided in two complementary sites (Reims University Hospital and Godinot Cancer Institute, Reims, France) which was located in a high COVID-19 incidence area during both peaks of the outbreak. RESULTS: A total of 26,566 patient's files were active during the year 2020. Breast screening (-19.5%), announcement dedicated consultations (-9.2%), Intravenous and Hyperthermic Intraoperative Intraperitoneal Chemotherapy (HIPECs) (-25%), and oncogeriatric evaluations (-14.8%) were heavily disrupted in regard to 2020 activity. We identified a clear second outbreak wave impact on medical announcement procedures (October, -14.4%), radiotherapy sessions (October, -16%), number of new health record discussed in multidisciplinary tumor board meeting (November, -14.6%) and HIPECs (November, -100%). Moreover, 2020 cancer care activity stagnated compared to 2019. DISCUSSION: The oncological care pathway was heavily disrupted during the first and second peaks of the COVID-19 outbreak. Between lockdowns, we observed a remarkable but non-compensatory recovery as well as a lesser impact from the pandemic resurgence. However, in absence of an increase in activity, a backlog persisted. CONCLUSION: Public health efforts are needed to deal with the consequences of the COVID-19 pandemic on the oncology care pathway.

Mathematical modeling of peripheral blood neutrophil kinetics to predict CLAD after lung transplantation.

BACKGROUND: The presence of neutrophils in the lung was identified as a factor associated with CLAD but requires invasive samples. The aim of this study was to assess the kinetics of peripheral blood neutrophils after lung transplantation as early predictor of CLAD. METHODS: We retrospectively included all recipients transplanted in our center between 2009 and 2014. Kinetics of blood neutrophils were evaluated to predict early CLAD by mathematical modeling using unadjusted and adjusted analyses. RESULTS: 103 patients were included, 80 in the stable group and 23 in the CLAD group. Bacterial infections at 1 year were associated with CLAD occurrence. Neutrophils demonstrated a high increase postoperatively and then a progressive decrease until normal range. Recipients with CLAD had higher neutrophil counts (mixed effect coefficient beta over 3 years = +1.36 G/L, 95% Confidence Interval [0.99-1.92], p < .001). A coefficient of celerity (S for speed) was calculated to model the kinetics of return to the norm before CLAD occurrence. After adjustment, lower values of S (slower decrease of neutrophils) were associated with CLAD (Odds Ratio = 0.26, 95% Confidence Interval [0.08-0.66], p = .01). CONCLUSION: A slower return to the normal range of blood neutrophils was early associated with CLAD occurrence.

[Antineoplastic drug induced nausea and vomiting: What is the clinical practice in 2018? An update of AFSOS clinical guidelines]. / Nausées-vomissements induits par les traitements anti-cancéreux (NVITAC) : quelle prise en charge en 2018 ? Mise à jour du référentiel AFSOS.

Antineoplastic drug induced nausea and vomiting (ANDINV) (previously named: Chemotherapy-induced nausea and vomiting [CINV]) are one of the most feared adverse effect for patients who begin treatment with anti-cancer treatments and their bad control have a negative impact in the management of these patients. In this review article, it is proposed an update of French-speaking Association for oncologic supportive care (AFSOS) clinical practice of CINV guidelines. This update became necessary for several reasons: newly available anti-emetic drugs; new data published about individual risk factors of CINV; new antineoplastic agents available; changing in emetic risk levels for some molecules in the international guidelines. To address these guidelines, the various clinical presentations of ANDINV and their intensity classification are discussed. Then, the different therapeutic solutions are presented: classes of conventional drug therapies, complementary therapies and advice to patients. Then, the implementation of primary prophylaxis are presented in four steps: (1) to evaluate the emetic risk level of antineoplastic agent; (2) to set the emetic risk level of antineoplastic protocols; (3) to set types of antiemetic drugs to implement; (4) "Outperform" prophylaxis in case of individual risk factors. Finally, implementation of secondary prophylaxis and rescue treatments are adressed.

Venous thromboembolism: What pharmacists know? What do they need?

INTRODUCTION: Venous thromboembolism is common in cancer. Low-molecular weight heparins are recommended for prolonged treatment (3-6 months or more if the cancer is active) and prevention of recurrence of venous thromboembolism in cancer. Community pharmacists are often faced with questions from patients. The main objective of this study was to describe the organization, practices and knowledge of pharmacists in care of venous thromboembolism in cancer patients. METHODS: A descriptive survey was conducted electronically in October and November 2013 with pharmacists in the Champagne-Ardenne region. The questionnaire collected data on the general organization of the pharmacy, management of outpatients with cancer and thrombosis, and the level of knowledge regarding recommendations on the management of thrombosis in patients with cancer. RESULTS: The participation rate was 31.6%. In 93% of cases, pharmacists had no particular expertise in oncology and/or supportive care. In addition, 96% did not know the existence of recommendations for "thrombosis in cancer." Finally, 49% gave the correct answer to the case report (low-molecular weight heparins). CONCLUSION: Training sessions on the management of venous thromboembolism in cancer are currently available to pharmacists in the region. A new assessment of knowledge will be performed at the end of the year 2014. This regional experience is now extended to a national level (all French regions).

Prevalence of hepatitis B and C and sensibility of a selective screening questionnaire in patients receiving chemotherapy for solid tumors.

BACKGROUND: Reactivation of hepatitis B or C virus can occur in patients undergoing chemotherapy. Recommendations for selective or systematic hepatitis B virus testing prior chemotherapy for solid tumors differ. The primary aim was to determine the seroprevalence of hepatitis B or C in a low endemic country. The second objective was to assess the relevance of a questionnaire on hepatitis B/C risk factors to consider a selective screening. METHODS: Patients were prospectively tested for hepatitis B/C markers. HBs antigen positive patients and isolated anti-HBc positive patients with detectable viral load received antiviral preventive treatment. Patients or physicians completed the questionnaire on infection risk factors. RESULTS: Among the 450 patients included, 388 were tested for all serological markers and had gastrointestinal (63.7%), lung (31.2%) and skin (4.6%) cancers. The prevalence of subjects exposed to hepatitis B virus was 8.5% (33/388). One patient tested positive for HBs antigen and received preventive treatment. Prevalence of subjects exposed to hepatitis C was 1.3% (5/388). The questionnaire sensitivity was 45.5%, 100% and 50% for detecting carriers of hepatitis B, C and one or the other, respectively. CONCLUSIONS: Seroprevalence of hepatitis B was low. Selective screening with the questionnaire was insufficiently sensitive. Systematic screening with serological tests prior to chemotherapy in patients with solid tumors is therefore relevant.

[Renovascular safety of bevacizumab in breast cancer patients. The prognostic value of hypertension and proteinuria]. / Tolérance rénovasculaire du bévacizumab dans le cancer du sein. Valeur pronostique de l'hypertension et de la proteinuria.

INTRODUCTION: The potential prognostic value of hypertension and proteinuria of anti-vascular endothelial growth factor (VEGF) drugs has not been assessed in routine clinical practice so far in breast cancer. The objectives of the MARS study were to assess the prevalence of proteinuria and hypertension at baseline, their incidence under anti-VEGF treatment, and to evaluate a possible link with overall survival. METHODS: Patients from 8 centres were included between 2009 and 2011 with a follow-up of 1 year. They were naive of any previous anti-VEGF treatment and planned to be started on one. The results of the group of patients with breast cancer receiving bevacizumab are presented. RESULTS: Four hundred and two patients with breast cancer and treated with bevacizumab were included. At inclusion, hypertension prevalence was 12.4%, proteinuria 23.9%. The incidence of de novo proteinuria and hypertension during the follow-up was 61.7% and 16.8%, respectively. Among patients with de novo proteinuria, 62.2% afterwards improved/normalized. No thrombotic microangiopathy was reported. Baseline or de novo proteinuria/hypertension were not associated with overall survival in breast cancer patients treated with bevacizumab. DISCUSSION: These results on the renovascular safety of bevacizumab in breast cancer patients showed that the prevalence of hypertension and proteinuria was high at baseline and, moreover, patients treated with bevacizumab frequently developed de novo hypertension and/or proteinuria. Finally, neither hypertension, nor proteinuria, neither at baseline, nor de novo, were associated with overall survival in our cohort of "real-life'' patients

Regorafenib as a single-agent in the treatment of patients with gastrointestinal tumors: an overview for pharmacists.

Regorafenib (BAY 73-4506, Stivarga® Bayer HealthCare Pharmaceutical Inc) is an oral multikinase inhibitor with a distinct and wide-ranging profile of tyrosine kinase inhibition, resulting in antiangiogenic and antiproliferative properties in tumors. Single-agent regorafenib administered as a 160-mg daily dose for the first 21 days of a 28-day cycle is approved for use in patients with pretreated metastatic colorectal cancer (mCRC) and gastrointestinal stromal tumor (GIST) progressing on imatinib and sunitinib, following publication of data from the phase III CORRECT and GRID studies respectively. Regorafenib is currently under phase III investigation in patients with hepatocellular carcinoma and is in several phase II studies in patients with gastrointestinal (GI) tumors. This review describes the clinical development of regorafenib in patients with GI cancers, and highlights the key issues important for the modern day clinical pharmacist who forms part of the multidisciplinary team ensuring safe and effective delivery of the drug to the patient. This information is considered of particular importance to the clinical pharmacist for the future development of regorafenib in this treatment setting.

[A new perspective in the treatment of non-small-cell lung cancer (NSCLC). Role of afatinib: An oral and irreversible ErbB family blocker]. / Nouvelle perspective de traitement dans le cancer bronchique non à petites cellules (CBNPC). Place de l'afatinib : un inhibiteur oral et irréversible de la famille ErbB.

Tyrosine kinase inhibitors (TKI) that block epidermal growth factor receptor (EGFR) pathway have demonstrated a clinical benefit for patients with non-small-cell lung cancer (NSCLC) harboring EGFR mutations. The currently available TKI (gefitinib and erlotinib) are EGFR reversible inhibitors. Afatinib is an oral, irreversible ErbB family blocker that covalently binds and blocks signaling from EGFR (ErbB1), HER2 (ErbB2) and ErbB4. The compound inhibits also the transphosphorylation of ErbB3. With this mode of action, afatinib is thought to have a mechanistic advantage over EGFR blockade alone, in that it provides a sustained, covalent inhibition of ErbB homo- and hetero-dimers. In the pivotal LUX-Lung 3 study, afatinib demonstrated a prolonged progression free survival over standard pemetrexed plus cisplatin chemotherapy (11.1 versus 6.9 months; HR = 0.58, 95% CI: 0.43-0.78; P = 0.001) in EGFR mutation positive NSCLC patients. The compound has recently been granted a marketing authorization (MA) for the treatment of patients with locally advanced or metastatic NSCLC with activating EGFR mutation(s) and EGFR TKI-naive. In this paper are summarized the efficacy and safety data in this indication.

Administration of intravenous iron complexes on implantable central venous access port in cancer patients in France: the FERPAC survey.

PURPOSE: Implantable central venous access port (portacath) is used to provide long-term venous access and to deliver chemotherapy in cancer patients. Intravenous iron complexes are frequently prescribed in this setting, and some physicians use a portacath for their administration. The aim of this survey was to assess the frequency of this practice and the reasons supporting it. METHODS: This declarative survey was conducted in France; 497 oncologists/hematologists were contacted to answer a survey on their practices regarding the administration of intravenous iron via a portacath. RESULTS: A total of 141 recipients (29.5 %) completed the questionnaire. The intravenous iron complexes most frequently used were iron sucrose and ferric carboxymaltose, and 55.2 % of the responders reported using a portacath to administer intravenous iron complexes. The main reasons mentioned for this practice were ease of administration (27.9 %) and preservation of venous capital (27.6 %). The main reasons reported for not using a portacath to administer intravenous iron were a history of thrombosis (45.1 %) or potential drug interactions (17.7 %). Efficacy and safety were expected to be similar to those observed with peripheral administration. A 47.6 % of physicians declared that they usually did not observe adverse reactions after use of a portacath for iron administration. Intravenous iron administration was always planned after chemotherapy for 46.6 % of the responders and before chemotherapy for 38.2 %, whereas 15.3 % did not have any preference for either option. CONCLUSIONS: Intravenous iron complexes (mainly iron sucrose and ferric carboxymaltose) are commonly administered through a portacath in cancer patients in France. The choice for this route of administration is supported by clinical considerations, but further studies are needed to confirm the efficacy and safety of this practice.

Colony stimulating factors (CSF) biosimilars. Progress?

Biosimilars are equivalent drugs for other biotechnological drugs for which patent has expired. These biopharmaceuticals are often looked upon as simple copies of parent drugs whose goal is solely to potentially generate costs savings. The expansion of available drugs is a subject of attention, criticism and quarrels, often related to a lack of product knowledge. These drugs are copies but need scientific development that must meet many strict rules. Many questions arise in connection with the marketing of several biosimilar drugs in the field of hematopoietic growth factors of white and red cells. Many of them should be discussed.

[Management of analgesics in cancer patients with renal impairment]. / Gestion des antalgiques chez les patients insuffisants rénaux en cancérologie.

Pain is frequent in cancer patients. To date, there is a consequent therapeutic arsenal so to manage pain; the different treatment strategies are the subject of various recommendations. Patients with cancer also frequently suffer from renal insufficiency, and this comorbidity may disrupt or jeopardize the analgesic strategy by changing the risk-benefit ratio of treatment options. This article provides recommendations for the use of drugs used for pain treatment after pointing out: 1) etiological and pathophysiological elements of pain; 2) therapeutic strategies for pain management; 3) data regarding renal failure in cancer and; 4) a point on drugs pharmacokinetics.

Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care.

Antineoplastic drugs used in the treatment of cancers present with variable renal tolerance profiles. Among drugs with a potential for renal toxicity, platinum salts, and especially cisplatin is a well-known agent that may induce acute and chronic renal failure. The mechanisms of its renal toxicity and the means of its prevention are presented in this article which represent the Clinical Recommendation from the Special Interest Group on Cancer Care of the European Society of Clinical Pharmacy (ESCP).

Development of a ready-to-use antibiotic conservation solution for arterio-venous grafts.

Although surgical procurement and conservation techniques have been improved, some organs or tissues might still become contaminated between procurement and grafting. To avoid such incident, the different procurement centres look forward to setting up precise decontamination protocols, in order to avoid the loss of already too-rare grafts. This precise goal led Reims University Hospital to develop an arterio-venous graft conservation solution. It is a frozen, ready-to-use antibiotics admixture in which arterial grafts are placed between procurement and freezing in the tissues bank. The stability study should allow a more rational use of this solution, determining an expiry date and a maximum delay of use after thawing. Cefotaxime and vancomycin assays were carried out with a high-performance liquid chromatography (HPLC)/UV method, whereas gentamicin was dosed using fluorescence polarization immunoassay (FPIA). Composed of vancomycin, cefotaxime, and gentamicin in an isotonic, buffered sodium chloride and glucose solution, the antibiotic graft conservation solution developed at Reims University Hospital is stable for 6 months at -20 degrees C and 24 h at room temperature after thawing. Solutions can not be frozen again after thawing. Although it does not contain macromolecules, as recommended by the Etablissement Français des Greffes, the developed solution is the sole one in France having had benefited from a stability study. Moreover, the different procurement teams are entirely satisfied with our solution.

Microbial growth tests in anti-neoplastic injectable solutions.

The Institut Gustave-Roussy (IGR) Department of Clinical Pharmacy (DCP) ensures the annual preparation of about 30 000 therapeutic batches of anti-neoplastic agents. High performance thin-layer chromatography (HPTLC) allows postproduction quality control of these batches. Although the centralized chemotherapy manufacturing unit has been recently ISO 9001:2000 certified, it was considered to improve the quality level of manufactured batches even further. The viability of micro-organisms (bacteria and fungi) in appropriate sterile media containing various anti-neoplastic agents at therapeutic concentration was assessed to demonstrate the lack of contamination during our manufacturing process in the isolator. After 14 days of incubation in these media, the results show the absence of contamination of the manufactured batches. This leads us to conclude that using sterile drugs and sterile medical devices in a sterile isolator allows the manufacture of sterile therapeutic batches with excellent confidence.

Incidence of renal insufficiency in cancer patients and evaluation of information available on the use of anticancer drugs in renally impaired patients.

BACKGROUND: Chronic renal failure is a common pathology. The high frequency of this disease in the general US population has been assessed in the NHANES III study. However, the frequency of chronic renal insufficiency among cancer patients remains unclear. MATERIAL/METHODS: 316 cancer patients were in a one-month study, included regardless of their pathology, treatment (antineoplastic drugs used or programmed to be used, pretreated, or no treatment), or any other criteria. RESULTS: Among the patients, 287 (90.8%) had normal serum creatinine levels (<110 micromol/l), i.e. a frequency of 9.2% for renal insufficiency in our population. However, when renal function was estimated by calculating creatinine clearance using the Cockcroft and Gault formula, 33% of the patients had an estimated GFR of less than 80 ml/min. Among these, 28% had a creatinine clearance ranging form 80 to 50 ml/min and 5% had a creatinine clearance of less than 50 ml/min. Renal insufficiency is frequent in cancer patients since almost one third of the patients present renal insufficiency. Furthermore, among patients with normal serum creatinine levels, one patient out of five has asymptomatic renal insufficiency. CONCLUSIONS: Therefore, it is of major importance that renal function be assessed by calculation of creatinine clearance using the Cockcroft and Gault formula in every patient, even when serum creatinine is within the normal range.

Contribution of high-performance thin-layer chromatography to a pharmaceutical quality assurance programme in a hospital chemotherapy manufacturing unit.

The Department of Clinical Pharmacy (DCP) in the Institut Gustave-Roussy (IGR) is equipped with a high-performance thin-layer chromatography (HPTLC) analytical platform. One of the numerous possible uses of HPTLC is post-production quality control of chemotherapy manufacturing. After 3 years of existence, routine validation of manufactured batches has attained considerable maturity: 24 cytotoxic agents can be controlled in terms of identity, purity and concentration. Approximately 50% of the sampled preparations are assessed. More than 97% were within specifications, 1.6% were not, probably due to incorrect homogenization before sampling; and 1% were not evaluable. Using HPTLC in a hospital manufacturing unit contributes to quality assurance programmes such as accreditation to which the IGR DCP is now committed but also ISO 9001:2000 certification concerning the chemotherapy manufacturing unit.