Absence of significant clinical benefit for a systematic routine creatine phosphokinase measurement in asymptomatic patients treated with anti-programmed death protein (ligand) 1 immune checkpoint inhibitor to screen cardiac or neuromuscular immune-related toxicities.

AIM: Despite unprecedented results of anti-programmed death protein (ligand) 1 (PD-(L)1) immune checkpoint inhibitor in the oncology's armamentarium, immune-related adverse events (irAEs) represent a therapeutic hurdle. Currently, there is no consensual recommendation on a routinely monitored biomarker to early detect irAE. Biological markers such as serum creatine phosphokinase (CPK) are commonly used to measure muscular tissue injury. The potential of routine serum CPK monitoring to predict cardiac or neuromuscular irAE in patients treated with immunotherapy remains unknown. METHODS: In this retrospective study between January 2016 and December 2018 at Gustave Roussy Cancer Campus, 1151 cancer patients treated with anti-PD-(L)1 immunotherapy were systematically monitored with serum CPK measurements before each immunotherapy cycle. We considered significant CPK increases according to Common Terminology Criteria for Adverse Events v5.0 (CTCAEV5) of grade ≥2 severity. Comparisons were performed in patients with immune-related CPK (ir-CPK) elevations symptomatic versus asymptomatic. RESULTS: Overall, 53 of 1151 (4.6%) patients showed a CPK increase. Elevations of CPK were deemed to be immunotherapy-related in 31 of 1151 (2.7%) patients. Among them, 12 of 31 (38.7%) patients experienced symptomatic cardiac or neuromuscular irAE, whereas the other 19 of 31 (61.3%) patients remained asymptomatic. In patients with symptomatic irAE, the mean ir-CPK level was higher compared with asymptomatic patients (1271 versus 771 UI/L, P value = 0.02). In the asymptomatic group, all patients experienced a spontaneous resolution of the ir-CPK increase, and none required medical intervention. CONCLUSION: Most patients with immune-related CPK increase remained asymptomatic. The CPK serum increase did not alter the clinical management of asymptomatic patients. The results of this study did not support a significant clinical interest for a systematic routine CPK monitoring in patients amenable to anti-PD-(L)1 immunotherapy.

FabAct®: a decision-making tool for the anticipation of the preparation of anticancer drugs.

RATIONALE: Due to the increase of new cancer cases, our chemotherapy compounding unit must face with ever-growing production needs. To support this increasing workload, we decided to anticipate the preparation of several anti-cancer drugs. AIMS AND OBJECTIVES: To help us in the decision making, we needed a modern tool able to combine several criteria for selecting appropriate medications for an anticipated preparation. The aim of this study was to assess the decision-making software, FabAct(®) (Version 1.0). METHODS: FabAct(®) ranked all of the anti-cancer drugs used in our chemotherapy compounding unit according to price, chemical stability, compounding difficulties, dosage and production per year. Then, we started to anticipate currently the preparation of four medications and conducted a follow-up of destroyed preparations between January and May 2007. We tried to identify the destruction causes and calculated the time saved for the patients and for the pharmacy technicians. RESULTS: According to the decision-making software, the first four drugs for an anticipated preparation were: fluorouracil, cisplatin, carboplatin and paclitaxel. A total of 3913 (50.2%) anticipated preparations were performed and among those, 470 (12%) were destroyed. The main cause of destruction was due to the preparation expiration. Finally, the mean waiting time per patient was reduced from 118 minutes to 68 minutes after the application of the anticipated model. CONCLUSION: According to this 5-month follow-up, FabAct(®) helped us to select appropriate anti-cancer drugs to anticipate the compounding. Most of the anticipated preparations were administrated to patients and the patient waiting time was significantly reduced.

The application of hazard analysis and critical control points and risk management in the preparation of anti-cancer drugs.

OBJECTIVE: To apply the Hazard analysis and Critical Control Points method to the preparation of anti-cancer drugs. To identify critical control points in our cancer chemotherapy process and to propose control measures and corrective actions to manage these processes. SETTING: The Hazard Analysis and Critical Control Points application began in January 2004 in our centralized chemotherapy compounding unit. From October 2004 to August 2005, monitoring of the process nonconformities was performed to assess the method. METHODS: According to the Hazard Analysis and Critical Control Points method, a multidisciplinary team was formed to describe and assess the cancer chemotherapy process. This team listed all of the critical points and calculated their risk indexes according to their frequency of occurrence, their severity and their detectability. The team defined monitoring, control measures and corrective actions for each identified risk. Finally, over a 10-month period, pharmacists reported each non-conformity of the process in a follow-up document. RESULTS: Our team described 11 steps in the cancer chemotherapy process. The team identified 39 critical control points, including 11 of higher importance with a high-risk index. Over 10 months, 16,647 preparations were performed; 1225 nonconformities were reported during this same period. CONCLUSIONS: The Hazard Analysis and Critical Control Points method is relevant when it is used to target a specific process such as the preparation of anti-cancer drugs. This method helped us to focus on the production steps, which can have a critical influence on product quality, and led us to improve our process.

Therapeutic strategy for treatment of metastatic non-small cell lung cancer.

OBJECTIVE: To review the current practices for metastatic non-small cell lung cancer (NSCLC) management and highlight the latest progress. DATA SOURCES: A literature review using HighWire Press (1960-May 2008) was conducted using the following key words: non-small cell lung cancer, chemotherapy, supportive care, therapeutic strategy, quality of life (QOL), and targeted therapies. STUDY SELECTION AND DATA EXTRACTION: Review articles, clinical trials, and case reports, as well as the references of those articles, were reviewed. Statistical significance and number of patients included in the studies were some of the aspects that were considered seriously. Response rates, overall survival, and progression-free survival were the major data considered. DATA SYNTHESIS: The therapeutic management of metastatic NSCLC has undergone a profound evolution over the past 10 years. The positive impact of chemotherapy on survival compared with supportive care alone has been demonstrated by several meta-analyses. The development of third-generation agents with better efficacy/toxicity ratios, such as vinorelbine, paclitaxel, docetaxel, gemcitabine, and pemetrexed, has led to improved therapeutic management of NSCLC, especially when tailored to patients' comorbidities and performance status. First-line platinum-based combinations remain the standard of care, with median survival 8 months and 1-year survival 35%, but no particular combination has yet shown superiority. First-line platinum regimens in combination with bevacizumab, a targeted inhibitor of vascular endothelial growth factor, have further improved NSCLC median survival. Moreover, second- and third-line treatments have evolved. The addition of small-molecule epidermal growth factor inhibitors and other targeted therapies has modified the pattern of NSCLC treatment. Specific management of the elderly and patients with poor performance status should be applied. CONCLUSIONS: Although there has been progress in the treatment of NSCLC, the gain in terms of clinical response and survival is still modest. Maintaining QOL and tailoring therapy for patients based on age, performance status, comorbidities, and toxicities, remain the first priority for clinicians.

[Misoprostol for treating postpartum hemorrhages]. / Le misoprostol dans le traitement curatif des hémorragies du post-partum.

Postpartum hemorrhage is defined by bleeding > 500 mL through the vagina. It is one of the obstetrical complications that obstetricians fear most. It is the leading cause of maternal mortality in the world, especially in developing countries. The reference treatments in France are parenteral oxytocin and sulprostone. Sulprostone involves sometimes fatal side effects, and must be administered only in appropriate health care facilities. It also has the major disadvantage of requiring refrigeration. Misoprostol has uterotonic properties that have led to its occasional off-label use in the treatment of postpartum hemorrhage, by rectal or sublingual administration, as an alternative to sulprostone. A careful review of the literature on this particular use of misoprostol is essential.