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Small-cell lung cancer (SCLC) accounts for approximately 15% of lung cancer and is associated with poor prognosis. In platinum-refractory or -resistant SCLC patients, few treatment options are available. Topotecan is one of the standards of care for these patients, however, due to its high toxicity, several different approaches are employed. FOLFIRI (folinate, 5-fluorouracil and irinotecan) is a chemotherapy regimen used in digestive neuroendocrine carcinoma, which shares pathological similarities with SCLC. In this retrospective study, we evaluated the efficacy and safety of FOLFIRI in patients with platinum-resistant/refractory SCLC. Medical records from all consecutive SCLC patients treated with FOLFIRI in a French University Hospital from 2013 to 2021 were analyzed retrospectively. The primary endpoint was the objective response rate according to RECIST v1.1 or EORTC criteria (ORR); secondary endpoints included duration of response, disease control rate, progression-free survival (PFS), overall survival (OS) and safety profile. Thirty-four patients with metastatic platinum-resistant (n = 14) or -refractory (n = 20) SCLC were included. Twenty-eight were evaluable for response, with a partial response observed in 5 patients for an overall ORR in the evaluable population of 17.9% (5/28) and 14.7% (5/34) in the overall population. The disease control rate was 50% (14/28) in the evaluable population. The median PFS and OS were 2.8 months (95%CI, 2.0–5.2 months) and 5.3 months (95%CI, 3.5–8.9 months), respectively. All patients were included in the safety analysis. Grade 3 or 4 adverse events occurred in 13 (38.2%) patients. The most common grade 3 or 4 adverse events were asthenia, neutropenia, thrombopenia and diarrhea. There was no adverse event leading to discontinuation or death. FOLFIRI showed some activity for platinum-resistant/refractory SCLC in terms of overall response and had an acceptable safety profile. However, caution is needed in interpreting this result. FOLFIRI could represent a potential new treatment for platinum-resistant/refractory SCLC patients. Further prospective studies are needed to assess the benefits of this chemotherapy regimen. FOLFIRI showed some activity for platinum-resistant/refractory SCLC in terms of overall response. FOLFIRI was well-tolerated in platinum resistant/refractory SLCL patients. FOLFIRI could represent a potential new treatment for SCLC, prospective studies are needed. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-FU)-induced hyperammonaemic encephalopathy is a rare but serious 5-FU adverse drug reaction (ADR). Given the growing number of cancers treated with 5-FU and the paucity of data regarding this ADR, we performed a retrospective national survey to better characterise 5-FU-induced hyperammonaemic encephalopathy. Since inception of the French pharmacovigilance database, we identified all patients who experienced 5-FU-induced hyperammonaemic encephalopathy. Variables regarding demographics, characteristics, management and outcome of patients were collected. From 1986 to 2018, 30 patients were included. 5-FU-induced hyperammonaemic encephalopathy started 2 [1–4] days after 5-FU infusion onset. Most common neurological disorders were consciousness impairment, seizures and confusion. hyperammonaemia tended to be higher in patients with the lowest Glasgow score and admitted in intensive care unit (ICU) compared to non-ICU patients (250 [133–522] versus 139 [68–220] μmol/L respectively, p = NS). Dihydropyrimidine dehydrogenase deficiency was found in 27% of tested patients (n = 3/11). Encephalopathy-induced mortality was 17%, 57% of patients were admitted in ICU and 70% had a complete neurological recovery within 5 [2–10] days. A 5-FU rechallenge was considered in 14 (67%) patients with neurological recovery and a relapse was observed in 57% of them. No 5-FU-induced hyperammonaemic encephalopathy relapse was observed as long as 5-FU rechallenge was performed with decreased 5-FU dosage. We report the largest cohort of 5-FU-induced hyperammonaemic encephalopathy cases so far. This ADR should be suspected and ammonaemia measured in all patients experiencing neurological disorders after 5-FU administration. In patients with complete neurological recovery, a 5-FU rechallenge could be cautiously considered. • Hyperammonaemic encephalopathy is a rare but serious adverse drug reaction of 5-FU. • It should be evoked in all patients with neurological disorders after 5-FU infusion. • Hyperammonaemia may result from Krebs cycle inhibition and/or urea cycle deficiency. • A complete neurological recovery is expected in properly managed patients. • A 5-FU rechallenge can be carefully considered in patients with neurological recovery. [ABSTRACT FROM AUTHOR]

Purpose: Fluoropyrimidines, oxaliplatin, irinotecan and targeted therapies represent the standard treatment of metastatic colorectal cancer. After failure of all these treatments, few options are available. In such chemorefractory patients the effect of triplet chemotherapy with bevacizumab (FOLFIRINOX bevacizumab) has never been investigated. Patients and Methods: 49 consecutive patients bearing unresectable metastatic colorectal cancer and who experienced failure to oxaliplatin- and irinotecan-based chemotherapy were treated with oxaliplatin (85 mg/m2), irinotecan (180 mg/m2), leucovorin (400 mg/m2), and fluorouracil (400 mg/m2 bolus then 2,400 mg/m2) repeated every 2 weeks. Results: Median age was 63 (range 36-82) years. After a median follow-up of 12 months, the median progression-free survival was 5.8 months (95% CI 3.4-6.8) and the median overall survival was 11.9 months (95% CI 8-18). The response rate after the cycle was evaluable for 36 patients, whereby we observed 18% (95% CI 8-35) partial or complete response, 45% (95% CI 28-68) stable disease of more than 2 months, and 37% (95% CI 21-58) progression. Conclusion: This study suggests that bevacizumab + FOLFIRINOX may be active in mCRC patients after failure of classical lines of chemotherapy. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: To compare the cost consequences of oral capecitabine and two different intravenous regimens of 5-fluorouracil/folinic acid (de Gramont and Mayo Clinic regimens) as adjuvant therapy in stage III colon cancer in France. Methods: Clinical efficacy and safety data were taken from published clinical trials. Medical resource use was estimated from published data and expert opinion. Direct costs (drug acquisition, inpatient and home drug administration, laboratory tests, transportation, and management of adverse events) were considered over a time horizon of 46 months (3.8 years). The perspective taken was that of the French Sickness Funds. Results: In patients treated with capecitabine, relapse-free survival was 1.3 months longer than with the Mayo Clinic regimen, which has been shown to be as effective as the de Gramont regimen. In the base case analysis, capecitabine was less costly (3,654 EUR/patient) than the Mayo Clinic (10,481 EUR/ patient) and de Gramont (7,204 EUR/patient) regimens. In the sensitivity analysis, capecitabine remained dominant except when the intravenous regimens were assumed to be administered at home in all patients. Conclusions: In France, capecitabine is more effective and less costly than both the Mayo Clinic and de Gramont regimens as adjuvant therapy for colon cancer. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Cetuximab plus platinum-based therapy (PBT) followed by cetuximab maintenance until progression (EXTREME) is a guideline-recommended first-line treatment option in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). DIRECT (Dose Intensity RElative to CeTuximab) was the first phase 4 observational study evaluating EXTREME administration in the real-world setting., Aims: The primary aim of this study was to assess the relative dose intensity of cetuximab in patients with R/M SCCHN treated with first-line cetuximab according to the EXTREME regimen., Methods and Results: Patients were ≥18 years old and eligible to receive cetuximab/PBT. Primary endpoint was cetuximab relative dose intensity (RDI). Of prospectively enrolled patients (n = 157), 119 received ≥1 cycle of EXTREME. Practices differing from the EXTREME trial were 5-fluorouracil omission (14%), maintenance cetuximab given every other week (54%), prior cetuximab, disease-free interval <6 months. 64% of patients reached cetuximab RDI ≥80%; mean cetuximab RDI was 88%. 46% of patients received maintenance cetuximab (mean RDI, 91%). Median progression-free survival and overall survival were 4.5 and 9.4 months. No new/unexpected safety findings were observed., Conclusions: The DIRECT study showed that first-line cetuximab plus PBT was a feasible, beneficial first-line treatment regimen in patients with R/M SCCHN in the real-world setting., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)