Adapted EXTREME regimen in the first-line treatment of fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (ELAN-FIT): a multicentre, single-arm, phase 2 trial.

BACKGROUND: A standard treatment for fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is yet to be established. In the previous EXTREME trial, few older patients were included. We aimed to evaluate the efficacy and tolerance of an adapted EXTREME regimen in fit, older patients with recurrent or metastatic HNSCC. METHODS: This single-arm, phase 2 study was done at 22 centres in France. Eligible patients were aged 70 years or older and assessed as not frail (fit) using the ELAN Geriatric Evaluation (EGE) and had recurrent or metastatic HNSCC in the first-line setting that was not eligible for local therapy (surgery or radiotherapy), and an Eastern Cooperative Oncology Group performance status of 0-1. The adapted EXTREME regimen consisted of six cycles of fluorouracil 4000 mg/m2 on days 1-4, carboplatin with an area under the curve of 5 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m2 on cycle 1-day 1, and 250 mg/m2 subsequently), all intravenously, with cycles starting every 21 days. In patients with disease control after two to six cycles, cetuximab 500 mg/m2 was continued once every 2 weeks as maintenance therapy until disease progression or unacceptable toxicity. Granulocyte colony-stimulating factor was systematically administered and erythropoietin was recommended during chemotherapy. The study was based on the two-stage Bryant and Day design, combining efficacy and toxicity endpoints. The primary efficacy endpoint was objective response rate at week 12 after the start of treatment, assessed by central review (with an unacceptable rate of ≤15%). The primary toxicity endpoint was morbidity, defined as grade 4-5 adverse events, or cutaneous rash (grade ≥3) that required cetuximab to be discontinued, during the chemotherapy phase, or a decrease in functional autonomy (Activities of Daily Living score decrease ≥2 points from baseline) at 1 month after the end of chemotherapy (with an unacceptable morbidity rate of >40%). Analysis of the coprimary endpoints, and of safety in the chemotherapy phase, was based on the per-protocol population, defined as eligible patients who received at least one cycle of the adapted EXTREME regimen. Safety in the maintenance phase was assessed in all patients who received at least one dose of cetuximab as maintenance therapy. The study is registered with ClinicalTrials.gov, NCT01864772, and is completed. FINDINGS: Between Sept 27, 2013, and June 20, 2018, 85 patients were enrolled, of whom 78 were in the per-protocol population. 66 (85%) patients were male and 12 (15%) were female, and the median age was 75 years (IQR 72-79). The median number of chemotherapy cycles received was five (IQR 3-6). Objective response at week 12 was observed in 31 patients (40% [95% CI 30-51]) and morbidity events were observed in 24 patients (31% [22-42]). No fatal adverse events occurred. Four patients presented with a decrease in functional autonomy 1 month after the end of chemotherapy versus baseline. During chemotherapy, the most common grade 3-4 adverse events were haematological events (leukopenia [22 patients; 28%], neutropenia [20; 26%], thrombocytopenia [15; 19%], and anaemia [12; 15%]), oral mucositis (14; 18%), fatigue (11; 14%), rash acneiform (ten; 13%), and hypomagnesaemia (nine; 12%). Among 44 patients who received cetuximab during the maintenance phase, the most common grade 3-4 adverse events were hypomagnesaemia (six patients; 14%) and acneiform rash (six; 14%). INTERPRETATION: The study met its primary objectives on objective response and morbidity, and showed overall survival to be as good as in younger patients treated with standard regimens, indicating that the adapted EXTREME regimen could be used in older patients with recurrent or metastatic HNSCC who are deemed fit with use of a geriatric evaluation tool adapted to patients with head and neck cancer, such as the EGE. FUNDING: French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer), Sandoz, GEFLUC, and GEMLUC. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Quality of life of patients with solid malignancies at 3 months after unplanned admission in the intensive care unit: A prospective case-control study.

BACKGROUND: Although short- and long-term survival in critically ill patients with cancer has been described, data on their quality of life (QoL) after an intensive care unit (ICU) stay are scarce. This study aimed to determine the impact of an ICU stay on QoL assessed at 3 months in patients with solid malignancies. METHODS: A prospective case-control study was conducted in three French ICUs between February 2020 and February 2021. Adult patients with lung, colorectal, or head and neck cancer who were admitted in the ICU were matched in a 1:2 ratio with patients who were not admitted in the ICU regarding their type of cancer, curative or palliative anticancer treatment, and treatment line. The primary endpoint was the QoL assessed at 3 months from inclusion using the mental and physical components of the Short Form 36 (SF-36) Health Survey. The use of anticancer therapies at 3 months was also evaluated. RESULTS: In total, 23 surviving ICU cancer patients were matched with 46 non-ICU cancer patients. Four patients in the ICU group did not respond to the questionnaire. The mental component score of the SF-36 was higher in ICU patients than in non-ICU patients: median of 54 (interquartile range: 42-57) vs. 47 (37-52), respectively (p = 0.01). The physical component score of the SF-36 did not differ between groups: 35 (31-47) vs. 42 (34-47) (p = 0.24). In multivariate analysis, no association was found between patient QoL and an ICU stay. A good performance status and a non-metastatic cancer at baseline were independently associated with a higher physical component score. The use of anticancer therapies at 3 months was comparable between the two groups. CONCLUSION: In patients with solid malignancies, an ICU stay had no negative impact on QoL at 3 months after discharge when compared with matched non-ICU patients.

Management of a Composite Pheochromocytoma (Pheochromocytoma/Neuroblastoma) in Adult Patient Recurring After Several Years: A Complex Case Report.

Pheochromocytoma/neuroblastoma composite tumors are rare entities for which little is known. We report an atypical case of a 39-year-old man with secondary bone locations of a composite tumor, 7 years after resection of adrenal neuroblastoma, with constitutional alteration of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 whose role is unknown. The diagnosis of a peripheral neuroblastic tumor in adulthood is difficult and even more so when it is a composite tumor. In the absence of a standard of care, management is varied and discussions about treatment modalities for these patients are complex.

Adolescents and Young Adults with Primary Brain Tumor: Description of the Care Pathway of Patients Diagnosed in Grenoble Between 2013 and 2019.

Purpose: This study was undertaken to describe the Adolescents and Young Adults' (AYA-aged patients') neuro-oncology care pathways at Grenoble Alpes University Hospital according to the French health recommendations. Methods: A retrospective monocentric observational study was conducted between 2020 and 2021, on patients 13-29 years of age, diagnosed from January 2013 to 2019 in our institute with a primary brain tumor, excluding meningiomas, schwannomas, and neurinomas. The detailed analysis took into account the type of care unit (adult or pediatric), whether or not a dedicated AYA support team was involved, and various pretherapeutic actions. Results: Sixty patients were included in this study. Three of the 9 key stages of the care process were completed regardless of the type of management. Management in a pediatric oncology department seems to improve multidisciplinary discussions and access to the AYA team. Collaboration with an AYA team seems to improve the recourse to pediatric advice and supportive care. Conclusions: Increased vigilance at all key steps as defined in the recommendations of the Directorate General of Healthcare Services would significantly improve the overall quality of care for this specific population. In the absence of a dedicated AYA hospitalization unit, interdisciplinary cooperation between the different professionals of the adult and pediatric services is essential, and the involvement of the AYA mobile team is a factor that favors links and exchanges and ultimately an overall improvement in patient care and life. We propose our vision of an ideal AYA neuro-oncology care pathway.

Paralytic ileus possibly associated with interaction between ritonavir/lopinavir and vincristine.

CASE DESCRIPTION: A French Caucasian man aged 39 with HIV infection was treated with abacavir/lamivudine and ritonavir/lopinavir. The patient (normal renal and liver functions) was diagnosed with a Burkitt lymphoma for which he was treated with cyclophosphamide day 1 to 5; doxorubicin day 1; methotrexate day 10; and vincristine day 1 and 8. At day 12, he suffered from abdominal pain associated with constipation. Paralytic ileus was diagnosed by study imaging. Ileus lasted 10 days necessitating parenteral feeding. Later on, a further cycle of chemotherapy with etoposide replacing vincristine was given and was well tolerated. CONCLUSION: We speculate that an interaction between ritonavir/lopinavir and vincristine was responsible for this severe toxicity. Vincristine is transported by P-gp and is metabolized via CYP3A5. Ritonavir is a potent CYP3A5 isoenzyme and P-gp inhibitor. Lopinavir is also a P-gp inhibitor. Ritonavir and lopinavir might have delayed vincristine elimination. Clinicians should be aware of this possible interaction.