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A major advance has been made in the management of rectal cancer, with the emergence in 2021 of total neoadjuvant treatment. The main publications from the RAPIDO and PRODIGE-23 trials reported a significant improvement in progression-free survival and the pathological complete response rate. The aim of this review is to synthesize recent data on neoadjuvant treatment of rectal cancer, to explain the long-term results of the RAPIDO and PRODIGE-23 trials, and to put them into perspective, considering current advances in de-escalation strategies. The update of the 5-year survival data from the RAPIDO trial highlights an increased risk of loco-regional relapse, with 11.7% of relapses in the experimental group and 8.1% in the control group, while the update of the PRODIGE-23 trial confirms the benefits of this treatment regimen, with a significant improvement in overall survival. In addition, the results of the OPRA and PROPSPECT trials confirm the benefit of total neoadjuvant treatment with induction chemotherapy, as well as the possibility of surgical de-escalation in the OPRA trial and radiotherapy in the PROSPECT trial. The challenge for the future is to identify patients who require total neoadjuvant treatment with the aim of curative surgery to obtain a cure without local or distant relapse, and those for whom therapeutic de-escalation can be envisaged., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: The management of upper aerodigestive tract cancers is a complex specialty. It is essential to provide an update to establish optimal care. At the initiative of the INCa and under the auspices of the SFORL, the scientific committee, led by Professor Béatrix Barry, Dr. Gilles Dolivet, and Dr. Dominique De Raucourt, decided to develop a reference framework aimed at defining, in a scientific and consensus-based manner, the general principles of treatment for upper aerodigestive tract cancers applicable to all sub-locations., Methodology: To develop this framework, a multidisciplinary team of practitioners was formed. A systematic analysis of the literature was conducted to produce recommendations classified by grades, in accordance with the standards of the French National Authority for Health (HAS)., Results: The grading of recommendations according to HAS standards has allowed the establishment of a reference for patient care based on several criteria. In this framework, patients benefit from differentiated care based on prognostic factors they present (age, comorbidities, TNM status, HPV status, etc.), conditions of implementation, and quality criteria for indicated surgery (operability, resectability, margin quality, mutilation, salvage surgery), as well as quality criteria for radiotherapy (target volume, implementation time, etc.). The role of medical and postoperative treatments was also evaluated based on specific criteria. Finally, supportive care must be organized from the beginning and throughout the patients' care journey., Conclusion: All collected data have led to the development of a comprehensive framework aimed at harmonizing practices nationally, facilitating decision-making in multidisciplinary consultation meetings, promoting equality in practices, and providing a state-of-the-art and reference practices for assessing the quality of care. This new framework is intended to be updated every 5 years to best reflect the latest advances in the field., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Context: The reform of the third cycle of medical studies in France has introduced of the "Junior Doctor" status during the concluding year of residency. We wish to evaluate its implementation for the first promotion of medical oncology residents during 2021-2022 in correlation with the published guidelines., Method: AERIO conducted a cross-sectional study among French medical oncology residents. The survey was released via social networks and emails., Results: Twenty-eight of 47 residents responded. The typical week involved one to two half-days of consultation, one dedicated to clinical research, one multidisciplinary team meetings, with the rest of time being occupied by day care (mostly) and hospitalization. Teaching and quality management activities were infrequent (monthly or less). The Junior Doctors rated their overall satisfaction at 8/10. A large majority (92.5 %) felt equipped to handle most of the situations they encountered. Almost all residents (92.9 %) had negotiated with their placement supervisor prior to the selection procedure. In one third of the cases (35.7 %), the principle of mismatch between the number of residents and the number of training sites was not respected. Only 42.9 % received training in scientific writing and 82.2 % of the residents agreed on the relevance of the post-internship training modules developed in other specialties., Conclusions: Junior doctors in medical oncology express overall satisfaction with this reform, which aligns with the recommendations. Nevertheless, certain concerns, such as selection procedure and inadequacy, along with areas requiring improvement, such as post-internship training and scientific writing, are clearly established., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The treatment of chronic myeloid leukemia relies on orally available tyrosine kinase inhibitors targeting the BCR::ABL1 oncoprotein. Bosutinib is a second generation adenosine triphosphate-competitive inhibitor approved for use in frontline adult chronic phase-chronic myeloid leukemia and all phases-chronic myeloid leukemia in the second line setting or beyond. Its efficacy was demonstrated in several pivotal clinical trials at 400mg once daily in the first line context and at 500mg once daily beyond first line. Bosutinib-related adverse events frequently occur early after treatment initiation and include gastro-intestinal symptoms and cytolytic hepatitis. These drug-related adverse events must be properly managed in order to preserve safety, efficacy and treatment acceptability. The French chronic myeloid leukemia study group gathered a panel of experts in hematology, pharmacology and hepatology in order to elaborate practical recommendations on the management of bosutinib treatment. These recommendations aim at optimizing the short and long-term tolerance and benefit/risk balance of bosutinib, mainly focusing at gastro-intestinal and liver toxicities., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Gastric cancer is the 6th most common cancer in the world. Gastric adenocarcinomas can be divided into two groups: gastroesophageal junction adenocarcinomas and distal gastric adenocarcinomas, with different risk factors and potentially different therapeutic strategies. Therapeutic strategy for esogastric adenocarcinoma is multimodal. Gastric adenocarcinomas are managed with surgery and peri-operative chemotherapy. Gastroesophageal junction adenocarcinomas can either be treated surgically after neoadjuvant chemoradiotherapy or in the same way than gastric adenocarcinomas. There is currently no evidence of superiority of either treatment strategy. Recently, nivolumab has been validated as an adjuvant therapy for patients with esophageal cancer who received preoperative chemoradiotherapy and had residual tumor on the surgical specimen. In the absence of preoperative treatment, adjuvant chemoradiotherapy or chemotherapy should be discussed on a patient-by-patient basis. Currently, there is not indication for targeted therapies, nor for adapting postoperative treatment according to the response to preoperative treatment. The only validated indication for immunotherapy is as adjuvant treatment of esophageal cancer, but many studies are ongoing and may change practices in the future. The objective of this review is to synthesize the literature concerning the management of localized esogastric adenocarcinoma., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Since the establishment of the reform of medical studies' third cycle in 2017, the first two residency semesters define the "phase socle" whose objective is to provide the basic knowledge of the specialty. We have carried out a declarative survey, submitted in 2020 to all French residents in Oncology whose "phase socle" had taken place during the first 3 years of the reform. The main objectives of this survey were to evaluate the theoretical teaching of oncology as well as the practical hospital training provided during this phase. The response rate was 44% (among 355 residents, 155 answered). In terms of theoretical training, the level of satisfaction with the national teaching courses of the Collège National des Enseignants en Cancérologie and the distant learning courses on the SIDES-NG platform was considered satisfactory (average visual analog scale of 6.7/10 and 5.7/10, respectively). There was greater heterogeneity in the organization of local courses, of which only 50% of base phase residents benefited. In terms of practical training, the training value of the medical oncology and radiation oncology residencies was good (visual analogue scale 7.9/10 and 6.7/10, respectively), with educational objectives adapted to the base phase, but with a greater workload for medical oncology. This study provides feedback that shows the success of this reform in oncology. It also offers suggestions, which could be the basis to improve the formation of oncology residents., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The management of patients with locally advanced rectal cancer has improved significantly in the past few years with preoperative radiotherapy (RT) and total mesorectal excision. The rate of local recurrence is now around 5 % while the risk of metastatic recurrence has not been reduced which is about 30 %. The benefit of adjuvant chemotherapy remains questionable apart from patients with ypN+tumor after preoperative chemoradiotherapy (CRT) for whom FOLFOX is an option. In recent years, several therapeutic trials have evaluated the benefit of extending the time between the end of RT and surgery and/or the benefit of neoadjuvant chemotherapy, administered as induction (before RT) or in consolidation (after RT and before surgery). The first results of two positive phase 3 trials, PRODIGE 23 and RAPIDO, have been reported in 2020. The two regimens evaluated in these trials are markedly different but have shown that neoadjuvant chemotherapy significantly reduces the risk of distant metastasis. Current developments largely related to a de-escalation of therapy: organ conservation according to a "Watch and Wait" strategy or local resection of the scar, administration of neoadjuvant chemotherapy without RT. These therapeutic strategies have not yet been validated but should be in the news tomorrow. The purpose of this review is to present recent data reported in patients with locally advanced rectal cancer., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

The COVID-19 pandemic has a major impact at all stages of cancer treatment. Risk of death from COVID-19 in patients treated for a cancer is high. COVID-19 vaccines represent a major issue to decrease the rate of severe forms of the COVID-19 cases and to maintain a normal cancer care. It is difficult to define the target population for vaccination due to the limited data available and the lack of vaccine doses available. It appears theoretically important to vaccinate patients with active cancer treatment or treated since less than three years, as well as their family circle. In France, patients actually defined at "high risk" for priority access to vaccination are those with a cancer treated by chemotherapy. A panel of experts recently defined another "very high-priority" population, which includes patients with curative or palliative first or second-line chemotherapy, as well as patients requiring surgery or radiotherapy involving a large lung volume, lymph nodes and/or of hematopoietic tissue. Ideally, it is best to vaccinate before cancer treatment. Despite the lack of published data, COVID-19 vaccines can also be performed during chemotherapy by avoiding periods of bone marrow aplasia and if possible, to do it in cancer care centers. It is necessary to implement cohorts with immunological and clinical monitoring of vaccinated cancer patients. To conclude, considering the current state of knowledge, the benefit-risk ratio strongly favours COVID-19 vaccination of all cancer patients., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Textbooks endorsed by national medical specialty societies and colleges are used as official references for faculty and national examinations. Oncology is transdisciplinary, practiced and taught by oncologists but also by other specialists. We aimed at identifying discrepancies between chapters on cancers in different official specialty textbooks and evaluating their impact on students., Material and Methods: Volunteer 6th-year medical students of the Sorbonne University faculty were paired and asked to list the discrepancies between all official specialty textbooks addressing a given cancer and then individually asked to evaluate the impact of discrepancies on their learning experience., Results: In March 2018, the 17 cancers listed in the French medical school education program were addressed in 14 official specialty textbooks (2 to 4 textbooks/cancer). Out of a class of 390 students, 78 volunteered and were paired; each cancer was analyzed by 3 pairs of students (1 or 2 cancers/pair); 154 discrepancies were reported (range: 4-18 per cancer). Discrepancies induced doubt and anxiety in students; 85% considered that harmonization should be achieved for all topics of the national medical school program., Conclusions: Discrepancies between official textbook are frequent, generate anxiety in students and impact learning experience., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: To evaluate the results of preoperative chemoradiation for resectable bulky cervical carcinoma without lymph node involvement after surgical lymph node staging., Patients and Methods: Between 2000 and 2010, 45 patients with cervical carcinoma stage IB2 (11 patients), IIA2 (3 patients) and IIB with proximal parametrial invasion (31 patients) were treated with pelvic radiation therapy at a dose of 40.5Gy and concurrent platin (44 patients) or mitomycin (one patient). Forty-two patients had low-dose-rate preoperative uterovaginal brachytherapy at a dose of 20Gy. All patients underwent hysterectomy. Three patients had postoperative low-dose-rate vaginal brachytherapy at a dose of 20Gy. The median follow-up was 34 months., Results: A pathologic cervical residual tumor was observed in 16 patients (35.6%). Six patients presented a relapse (13.3%) with a median delay of 8 months. The 5-year overall survival and disease free survival rates were 88.4% and 84.7%, respectively. In univariable analysis, a cervical residual tumor was the only predictive factor of overall survival (P=0.03). Late toxicity was observed in seven patients., Conclusion: Chemoradiation followed by surgery for resectable bulky stage I-II cervical carcinoma without lymph node involvement on pretreatment surgical staging can be used with a good local control and a high rate of 5-year overall survival., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Tyrosine kinase inhibitors targeting the BCR-ABL oncoprotein represent an outstanding progress in chronic myeloid leukemia and long-term progression-free survival has become a reality for a majority of patients. However, tyrosine kinase inhibitors may at best chronicize rather than cure the disease thus current recommendation is to pursue treatment indefinitely. As a consequence, high quality treatment and care must integrate optimal disease control and treatment tolerability. Tyrosine kinase inhibitors have an overall favorable safety profile in clinical practice since most adverse events are mild to moderate in intensity. However, recent evidence has emerged that new generation tyrosine kinase inhibitors may sometimes damage vital organs and if not adequately managed, morbidity and mortality may increase. The 2nd generation tyrosine kinase inhibitor nilotinib is licensed for the treatment of chronic myeloid leukemia with resistance or intolerance to imatinib and newly diagnosed chronic phase-chronic myeloid leukemia. Nilotinib represents an important therapeutic option but it is associated with an increased risk of cardiovascular events. The purpose of this article by the France Intergroupe des Leucémies Myéloïdes Chroniques is to provide an overview of nilotinib efficacy and cardiovascular safety profile and to propose practical recommendations with the goal to minimize the risk and severity of cardiovascular events in nilotinib-treated patients., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Circulating (CTC) and disseminated tumor cells (DTC) represent two different steps of the metastatic process. As with other types of cancer, the recent development of techniques for the detection of CTC and DTC respectively in the blood and bone marrow of patients generated many results in digestive cancers. However, the interpretation of these results and of the prognostic value of CTC/DTC is often limited by the small cohort size and the heterogeneity of detection methods. The aim of this article is to review the different results and their clinical impact, and discuss the possible use of CTC and DTC as new biomarkers. First of all, it is important to take into account the variability of epithelial markers used for the initial stage of immunoselection of CTC/DTC as well as that of molecular or cytological markers used for the second stage of detection. In esophageal, gastric, pancreatic and hepatocellular carcinomas, and in the ileal and pancreatic neuroendocrine tumors, some studies showed a correlation between the detection of CTC and/or DTC and a clinical pejorative course, whether these tumors were at localized or metastatic stages. On colorectal cancer in the adjuvant setting, a recent meta-analysis showed an association between the detection of CTC in peripheral blood and disease-free survival or overall survival. These results are consistent with those of a study that identified detection of CTC as a prognostic factor for relapse in stage II. This last study concluded that it was necessary to achieve long-term evaluation of CTC as a biomarker to guide the decisions of chemotherapy for stage II. In metastatic colorectal cancer, the FDA approved in 2007 the use of pretherapeutic levels of CTC and its variations per-treatment, determined by CellSearch(®) technology, as a tool in treatments management. However, the modalities of this monitoring have to be specified and clinical benefit or the cost-effectiveness of a treatment based on this new biomarker has to be evaluated. Finally, the qualitative and quantitative monitoring of CTC could be a non-invasive tool to monitor changes in tumor biology throughout the disease, and thereby improve the understanding of the processes of dissemination and therapeutic resistance.

Nilotinib (Tasigna) is a second-generation BCR-ABL kinase inhibitor, recently introduced and used for the treatment of chronic or accelerated phase CML patients, intolerant or resistant to imatinib. This treatment represents and important step forward for the disease control of such patients but can lead to side effects, sometimes serious, which can limit its optimal use. We propose here some guidelines that might be of help in daily practice, in order to manage properly these side effects.

The head-and-neck squamous-cell carcinomas (HNSCC) represent in order of frequency the fourth leading cause of cancer deaths among men in France. The term HNSCC includes various anatomopathological and clinical entities with different evolution patterns. For this reason, it is necessary to identify prognostic and predictive factors able to help in the choice of the treatment. The clinical factors with a prognostic value are the tumor location, the tumor size and the lymph node status. The degree of differentiation is the most important histologic factor. More recently, the identification of molecular factors has opened the way to new therapies. Thus, the overexpression of EGFR is associated with a poor prognosis. Its inhibition improves the survival of patients. p53 mutations and cyclin D1 amplification are actually subject to intensive research. The tumors associated with HPV infection are distinguishable by a better prognosis. 18-alpha-FDG positron emission tomography emerges as a useful tool for the therapeutic evaluation. The evolution of surgical techniques, the development of induction chemotherapy regimen or concurrent ones with radiotherapy and new techniques of conformal irradiation also results in a better locoregional control.

Introduction: At the request of the National Thesaurus of Gastrointestinal Cancer (TNCD), the SOR program undertaken by the French Federation of Cancer Centers (FNCLCC) and now led by the French National Cancer Institute (INCa), completed a systematic review to evaluate the value of chemoradiotherapy (CRT) in the management of locally advanced pancreatic adenocarcinoma in collaboration with clinician experts., Methods: Results of a systematic literature search using Medline (from 1980 to 2008) were completed by a consult of evidence-based medicine websites. All phase III randomized trials and systematic reviews concerning non resectable locally advanced pancreatic adenocarcinoma and non metastatic (stage III) were included in the study. Some phase II trials were also included if no phase III trials were retrieved. The following interventions were compared: CRT versus best supportive care (BSC), CRT versus radiotherapy, and CRT versus chemotherapy. The modalities of CRT regimens and the sequences of chemotherapy-CRT versus CRT were also studied. The quality and clinical relevance of the trials were evaluated using validated checklists, allowing associating each result with a level of evidence. Data synthesis was performed considering both efficacy and toxicity outcomes for each intervention., Results: Nineteen references were included in this systematic review: 2 meta-analyses, 11 randomized trials, 5 non-randomized trials and 1 randomized trial only published in abstract form. After a clinical and methodological critical appraisal, compared to the alternative BSC, concomitant CRT increases overall survival (C). Concomitant CRT compared to the radiotherapy alone increases the overall survival (B1) but is more toxic (B1). Concomitant CRT compared to chemotherapy alone is not superior in terms of survival (B1) and increases toxicity (A). Concerning administration modalities of radiotherapy, recent data are in favour to a limited irradiation to the tumoral volume (C) and to a total dose of 50-60 Gy in association with 5-FU. The study of radiotherapy associated drugs shows that 5-FU is the reference (B1) and the value of gemcitabine must be proved in randomized trials. Finally, the study of sequences chemotherapy-CRT has recently showed that induction chemotherapy before CRT improves survival (C). Validation of this strategy in a randomized trial is warranted., Conclusion: The use of CRT for locally advanced pancreatic adenocarcinoma is based on a few randomized trials even if this treatment appears superior in terms of survival compared to BSC and radiotherapy alone. This review shows the need to conduct other specific randomized trials in order to validate the value of CRT, especially compared to chemotherapy alone.

Dasatinib (Sprycel) is a new-targeted therapy used since 2005 in the treatment of chronic myelogenous leukemia and de novo Philadelphia positive acute lymphoblastic leukaemia patients, intolerant or resistant to imatinib. Despite its high efficacy in such patients in terms of hematologic, cytogenetic and molecular responses, the onset of frequent and sometimes serious side effects particularly in advanced phase patients, especially myelosuppressions and pleural effusions, may impair optimal administration of the drug. Recently, dasatinib dose optimisation in chronic-phase has reduced the incidence of such adverse events without modification of the efficacy, however, their optimal overall management can efficiently reduce their severity and minimize their impact on disease response. Hereby, we attempted to propose a series of guidelines that might be of help in daily practice, in order to control properly these side effects.

About 5,300 new cases of pancreatic adenocarcinomas are diagnosed each year in France. At the time of diagnosis, an efficient carcinologic surgery will not be possible for nearly 80% of patients, in relation to locoregional extension or metastatic dissemination. After surgical resection, the median survival of resected patients ranges from 12 to 20 months, with a high rate of loco-regional or metastatic relapses. Numerous therapeutic trials, adjuvant or neo-adjuvant, have been conducted in aim of which to improve locoregioanl control and survival rates. Chemotherapy and chemoradiotherapy represent adjuvant treatments. In one trial, a chemotherapy regimen with 5-fluorouracil and folinic acid (FUFOL) has proven its efficience for survival improvement by comparison to chemoradiotherapy and is at this time the reference treatment in Europe. In another trial, using adjuvant gemcitabine results in an improvement in disease-free survival. Some phase III trials are in progress to evaluate new therapeutic strategies. The aim of neoadjuvant strategy using chemoradiotherapy is to enhance the rate of complete resections and by the way local control. This is under evaluation. This paper presents a summary of adjuvant and neoadjuvant trials for patients with potentially resectable pancreatic adenocarcinoma.

Gemcitabine is a well-tolerated anti-tumour drug with broad-spectrum activity. It is now recommended for treatment in an increasing number of tumours. Locally advanced or metastatic pancreatic cancer is the only digestive cancer for which it has yet been approved. Numerous phase III trials have addressed gemcitabine's dosage, infusion modalities, and its potential association with other anti-tumour drugs in pancreatic cancer. Standard recommended treatment for this disease in 2006 is gemcitabine monotherapy following Burris'protocol, that is 1000 mg per square meter in a 30 minute-infusion weekly for seven weeks, one week off and then weekly for three weeks, repeated every 4 weeks. Many phase I or II trials have been carried out in all other digestive cancers. They show gemcitabine's potential activity, especially in esophageal cancer, biliary tract adenocarcinoma and hepatocellular carcinoma. Nevertheless, larger studies are required to confirm this efficacy. The aim of this review is to describe the trials that have contributed to determine gemcitabine's infusion modalities in pancreatic cancer. We will then present the studies that have been carried out in other digestive cancers.

Rituximab (Mabthera) is used in the treatment of refractory low-grade non-Hodgkin's lymphoma or in case of relapse after chemotherapy. Among the different adverse reactions with this drug, the most common is a constellation of symptoms (fever, rigors and chills) that occur more frequently during administration of the first dose of drug. These symptoms could be related to a cytokine-release syndrome. We report the case of a 46 year-old patient, presenting a familial cardiomyopathy, deceased a few minutes after having developed this syndrome, at the time of the 2nd infusion of rituximab. Several hypothesis have been suggested to explain this sudden death: a cardiac failure following deterioration of the systolic function, potentially related to the negative inotropic effects of TNFalpha, and/or an impairment of the diastolic function following the volemic overload. The impact of the reflex "administration of monoclonal antibody/cytokine-release syndrome" was only little investigated under physiologic or pathologic conditions. In spite of a risk of adverse reactions apparently moderated compared to the other drugs used in this context, this case report underlines the need for a special attention when using rituximab among patients with cardiac risk factors (reassessment of the benefit-risk ratio, specific monitoring, pre medication). More generally, it underlines the need for a systematic and continuous identification and reporting of adverse drug reactions to the French network of regional pharmacovigilance centres.

Although the term "targeted therapy" is used to described new molecular approaches derived from the recent increase in the knowledge of cancer biology, radiation therapy is a "targeted therapy" used against cancer. Dose fractionation changes and time treatment duration modifications are used to specifically increase the anti tumor effects of ionising radiation while minimising normal tissue impact of these changes. The implementation of 3 dimensional radiation therapy and IMRT allowed specific tumor targeting and tumor radiation dose increase with normal tumor surrounding tissue relative protection. Clinical research has widely used those concepts with the development of hyper fractionation which showed positive results for head and neck tumours in clinical trials. The development of IMRT has allowed tumor dose escalation in the case of prostate cancer without significant increase in normal tissue toxicity. Beside these approaches, a better understanding of cancer biology and in particular of tumor radiation resistance mechanisms led to the identification of new molecular targets that could be used to increase the therapeutic ratio of radiation therapy. These approaches attempt to widen the therapeutic ratio of radiation, i.e. to increase specifically tumor radiation response with little impact on normal tissue response.

We report on a case of methotrexate (MTX) intoxication occurring in a 19-year-old man treated for a leukemia. Exchange-transfusion (ET) was performed in attempt to remove the MTX from the body. This exchange-transfusion was unable to decrease the MTX plasma concentration. This inefficacy of ET in MTX intoxication is in contradiction with previously reported recommendations. However, this result is easily explained by MTX pharmacokinetics parameters.