• Humans
• Irinotecan/pharmacokinetics
• Irinotecan/administration & dosage
• Peritoneal Neoplasms/secondary
• Peritoneal Neoplasms/drug therapy
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/pathology
• Male
• Middle Aged
• Female
• Aged
• Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics
• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Adult
• Camptothecin/analogs & derivatives
• Camptothecin/pharmacokinetics
• Camptothecin/administration & dosage
• Camptothecin/therapeutic use
• Models, Biological
• Bevacizumab/pharmacokinetics
• Bevacizumab/administration & dosage
• Bevacizumab/therapeutic use
• Leucovorin/pharmacokinetics
• Leucovorin/administration & dosage
• Leucovorin/therapeutic use
• Fluorouracil/pharmacokinetics
• Fluorouracil/administration & dosage
• Injections, Intraperitoneal
• Organoplatinum Compounds

• Drug glucuronidation
• Drug metabolism
• Drug-drug interactions
• Enzyme induction
• Enzyme inhibition
• Glucuronide
• Metabolism-transport interplay
• Regulatory guidance
• UDP-glucuronosyltransferase
• UDP-glycosyltransferase

• TQ-B3203
• camptothecin
• model application
• model validation
• population pharmacokinetic model

Patients with advanced gastrointestinal cancer must cope with the negative effects of cancer and complications.

To evaluate psychological distress, quality of life, and coping strategies in patients with advanced colorectal cancer compared to non-colorectal cancer based on sex.

A prospective, transversal, multicenter study was conducted in 203 patients; 101 (50%) had a colorectal and 102 (50%) had digestive, non-colorectal advanced cancer. Participants completed questionnaires evaluating psychological distress (Brief Symptom Inventory-18), quality of life (EORTC QLQ-C30), and coping strategies (Mini-Mental Adjustment to Cancer) before starting systemic cancer treatment.

The study included 42.4% women. Women exhibited more depressive symptoms, anxiety, functional limitations, and anxious preoccupation than men. Patients with non-colorectal digestive cancer and women showed more somatization and physical symptoms than subjects with colorectal cancer and men. Men with colorectal cancer reported the best health status.

The degree of disease acceptance in gastrointestinal malignancies may depend on sex and location of the primary digestive neoplasm. Future interventions should specifically address sex and tumor site differences in individuals with advanced digestive cancer.

• Anxiety
• Colorectal cancer
• Depression
• Gastrointestinal cancer
• Sex

• CYP3A inducers
• cardiovascular diseases
• drug interactions
• hepatotoxicity
• irinotecan
• liver metastasis

• CPT-11
• FOLFIRI
• FOLFIRINOX
• Nonlinear mixed effect modelling
• Population pharmacokinetics

Background: The combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is a very effective chemotherapeutic regimen for unresectable pancreatic cancer. Previous studies have reported that female gender may be a predictor of a better response to FOLFIRINOX. This study was aimed at investigating the clinical outcomes and dose modification patterns of FOLFIRINOX by gender. Methods: Patients with metastatic pancreatic cancer (MPC) who began FOLFIRINOX as the first-line therapy at Seoul National University Bundang Hospital between 2013 and 2018 were enrolled. The patients received at least four chemotherapy cycles. Local regression and a linear mixed model were used to analyze dose modification patterns by gender. Results: Ninety-seven patients with MPC (54 men; 43 women) were enrolled. In the first FOLFIRINOX cycle, there were significant differences in age and body surface area between the genders (58.8 (men) and 64.9 years (women), p = 0.005; 1.7 (men) and 1.6 m² (women), p < 0.001, respectively). The median progression-free survival (PFS) and overall survival (OS) were 10.8 and 18.0 months, respectively. There was a trend of longer PFS (10.3 (men) and 11.9 months (women), p = 0.153) and a significantly longer OS (17.9 (men) and 25.9 months (women), p = 0.019) in female patients. During the first year of FOLFIRINOX treatment, there was a significant difference of the age-corrected dose reduction pattern by gender (a mean of 95.6% dose at the initial cycle and −0.35% of dose reduction per week in men versus a mean of 90.7% dose at the initial cycle and −0.53% of dose reduction per week in women, p-value of the slope: <0.001). There was no difference in the adverse event rates between the genders. Conclusions: Female patients showed longer OS despite a more rapid dose reduction during each cycle. Gender differences should be considered during FOLFIRINOX treatment.

• FOLFIRINOX
• chemotherapy
• gender
• pancreatic cancer

More and more relapsing or refractory pediatric cancers are described to present hypoxic features linked to a worse outcome. Therefore, the aim of our phase I study RAPIRI was the targeting of the central node mTor/HIF-1α with rapamycin plus irinotecan and determine the appropriated dose of this combination. As expected, the tolerance was optimal across all dose levels and no maximum tolerated dose of both drugs was reached. The pharmacokinetics (PK) helped us to refine the doses to use in the future phase II trial and the importance of PK follow-up in such combination. We also confirmed in almost half of the interpretable patients for tumor response a non-progressive disease. All those observations additionally to the ancillary’s studies provide strong evidence to propose a next trial focusing on brain tumors and sarcomas and using biweekly 125 mg/m² irinotecan dose with a PK follow-up and a rapamycin dose of 1.5 mg/m²/day, reaching a blood concentration above 10 µg/L.

Hypoxic environment is a prognostic factor linked in pediatric cancers to a worse outcome, favoring tumor progression and resistance to treatments. The activation of mechanistic Target Of Rapamycin (mTor)/hypoxia inducible factor (HIF)-1α pathway can be targeted by rapamycin and irinotecan, respectively. Therefore, we designed a phase I trial associating both drugs in pediatric refractory/relapsing solid tumors. Patients were enrolled according to a 3 + 3 escalation design with ten levels, aiming to determine the MTD (maximum tolerated dose) of rapamycin plus irinotecan. Rapamycin was administered orally once daily in a 28-day cycle (1 to 2.5 mg/m²/day), associating biweekly intravenous irinotecan (125 to 240 mg/m²/dose). Toxicities, pharmacokinetics, efficacy analyses, and pharmacodynamics were evaluated. Forty-two patients, aged from 2 to 18 years, were included. No MTD was reached. Adverse events were mild to moderate. Only rapamycin doses of 1.5 mg/m²/day reached over time clinically active plasma concentrations. Tumor responses and prolonged stable disease were associated with a mean irinotecan area under the curve of more than 400 min.mg/L. Fourteen out of 31 (45.1%) patients had a non-progressive disease at 8 weeks. Most of them were sarcomas and brain tumors. For the phase II trial, we can then propose biweekly 125 mg/m² irinotecan dose with a pharmacokinetic (PK) follow-up and a rapamycin dose of 1.5 mg/m²/day, reaching a blood concentration above 10 µg/L.

• HIF1
• intra-tumor hypoxia
• mTor
• pediatric refractory cancers

• gender
• gender medicine
• oncology
• pharmacology
• sex

• Body Composition
• Decision Making
• Female
• Humans
• Male
• Medical Oncology/trends
• Neoplasms/epidemiology
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/therapy
• Physicians
• Sex Characteristics
• Treatment Outcome

Since its clinical introduction in 1998, the topoisomerase I inhibitor irinotecan has been widely used in the treatment of solid tumors, including colorectal, pancreatic, and lung cancer. Irinotecan therapy is characterized by several dose-limiting toxicities and large interindividual pharmacokinetic variability. Irinotecan has a highly complex metabolism, including hydrolyzation by carboxylesterases to its active metabolite SN-38, which is 100- to 1000-fold more active compared with irinotecan itself. Several phase I and II enzymes, including cytochrome P450 (CYP) 3A4 and uridine diphosphate glucuronosyltransferase (UGT) 1A, are involved in the formation of inactive metabolites, making its metabolism prone to environmental and genetic influences. Genetic variants in the DNA of these enzymes and transporters could predict a part of the drug-related toxicity and efficacy of treatment, which has been shown in retrospective and prospective trials and meta-analyses. Patient characteristics, lifestyle and comedication also influence irinotecan pharmacokinetics. Other factors, including dietary restriction, are currently being studied. Meanwhile, a more tailored approach to prevent excessive toxicity and optimize efficacy is warranted. This review provides an updated overview on today’s literature on irinotecan pharmacokinetics, pharmacodynamics, and pharmacogenetics.

• Antiepileptic drugs
• Brain tumors
• Epilepsy
• Interaction
• Quality of life
• Side effects