"The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid." (MeSH 2013)
Latest Research Publications
Web Resources: Leucovorin (5 links)
This list of publications is regularly updated (Source: PubMed).
Patient-tailored FOLFIRINOX as first line treatment of patients with advanced pancreatic adenocarcinoma.
Medicine (Baltimore). 2019; 98(16):e15341 [PubMed] Free Access to Full Article Related Publications
Induction of CD3+ and FoxP3+ T Cells in Left-sided Colorectal Tumors After UFT/LV Chemotherapy.
Anticancer Res. 2019; 39(4):1997-2005 [PubMed] Related Publications
PATIENTS AND METHODS: Data of 260 patients with stage II or stage III colorectal cancer were analyzed. Gene expression and amount of TILs were evaluated using real-time reverse transcription polymerase chain reaction (CRT-PCR) assay and immunohistochemical staining, respectively.
RESULTS: Expression of CTLA4 and LAG3 in tumor tissues was significantly increased after UFT/LV chemotherapy, but only in left-sided tumors. The percentage of high-TIL, high-CD3 and high-FoxP3 patients in the UFT/LV group was significantly higher than that in the control group, only in left-sided tumors.
CONCLUSION: The increase in TILs count, especially of CD3+ T cells and FoxP3+ regulatory T cells, after UFT/LV chemotherapy were specific to left-sided colorectal cancers.
Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin in Hepatocellular Cancer with Extrahepatic Spread.
J Vasc Interv Radiol. 2019; 30(3):349-357.e2 [PubMed] Related Publications
MATERIALS AND METHODS: This single-center retrospective study comprised 116 patients with advanced HCC with both intrahepatic tumor and EHS (EHS group; n = 50) or with intrahepatic tumor only (non-EHS group; n = 66) treated with HAIC including oxaliplatin, fluorouracil, and leucovorin between June 2014 and July 2016. Overall survival (OS) and radiologic responses to treatment were determined and compared between the 2 groups.
RESULTS: Both the objective response rate and the clinical benefit rate were higher in the non-EHS group than in the EHS group (37.9% vs 16% objective response rate, P = .010; 81.8% vs 62% clinical benefit rate, P = .017). Median OS was not statistically different between the 2 groups (14.8 months vs 9.8 months, P = .068). Subgroup analysis of OS found that patients with lung metastases survived for a shorter time (OS 7 months) than patients with other metastatic sites (P = .003) and patients free of metastases (P = .001).
CONCLUSIONS: HAIC is a potential treatment option for advanced HCC with limited extrahepatic metastases in a population with hepatitis B virus infection.
Synergic and comparative effect of 5-fluorouracil and leucoverin on breast and colon cancer cells through TRPM2 channels.
Bratisl Lek Listy. 2018; 119(11):692-700 [PubMed] Related Publications
BACKGROUND: 5-FU and LV are widely used in breast and colon cancers for chemotherapy. It has been reported that the expression of TRPM2 channels increased intensively in cancer cells.
METHODS: Breast (MCF7) and colon (Caco-2) cells were cultured and divided into seven main groups. The cells in the group were incubated with 5-FU and LV for 24 hrs and then incubated with Antranilic acid. The effects of medicines were investigated on all molecular pathways of apoptosis.
RESULTS: It was found that 5FU and LCV, administered separately and together on breast cancer cell culture and colon cancer cell culture increased the intracellular calcium levels by stimulation of TRPM2 channels in both cancer cells.
CONCLUSION: As the result of our study, it has been shown that apoptotic effects of 5FU and LV on both colon and breast cancer cells were directly related to TRPM2 channels and that TRPM2 channels played an important role in the whole molecular pathway of apoptosis leading to increased intracellular Ca2+ (Ca2+) levels and increased mitochondrial depolarisation (Fig. 6, Ref. 43).
Oncologic outcomes after adjuvant chemotherapy with capecitabine compared to 5-fluorouracil/leucovorin for geriatric stage II colon cancer: a retrospective cohort study.
Int J Colorectal Dis. 2019; 34(4):629-639 [PubMed] Related Publications
METHODS: Patients over 70 years of age diagnosed with primary pathologic stage II colon cancer at the Seoul National University Hospital from January 2005 to December 2015 were included. A prospectively collected database was analyzed retrospectively. Patients were separated into an FL group and a capecitabine group. The primary outcomes were RFS, CSS, and OS.
RESULTS: Of the 154 included patients, 96 patients received FL and 58 patients received capecitabine. There was no difference between the two groups in RFS, CSS, or OS (p = 0.763, p = 0.221, and p = 0.470, respectively) as measured by Kaplan-Meier analysis with log-rank test. Administration of capecitabine as compared to FL was not a factor affecting RFS (hazard ratio [HR] 0.503, 95% confidence interval [CI] 0.145-1.745), CSS (HR 1.519, 95% CI 0.348-6.629), or OS (HR 0.941, 95% CI 0.290-3.053) on multivariable analysis.
CONCLUSIONS: Capecitabine is a safe regimen in terms of oncologic outcomes compared with FL in older patients with stage II colon cancer.
Nab-paclitaxel and gemcitabine or FOLFIRINOX as first-line treatment in patients with unresectable adenocarcinoma of the pancreas: does sequence matter?
BMC Cancer. 2019; 19(1):28 [PubMed] Free Access to Full Article Related Publications
METHODS: Eighty-three patients were treated with locally advanced or metastatic adenocarcinoma of the pancreas with either FOLFIRINOX or nab-Paclitxel and Gemcitabine (nabPGem) as first- or second line therapy. We analysed the outcome for OS and progression-free survival (PFS) in terms of treatment regimen and sequence.
RESULTS: The majority of patients presented in good performance status (PS) with a median age of 68 years. Fourty-two patients received FOLFIRINOX as first-line therapy, 41 patients were treated with nabPGem as first line therapy. Forty-eight patients received both treatments. The OS of all 83 patients was 12.6 months (95% CI: 10.7-14.6), resulting in a 1-year OS of 54%. Forty-eight patients received FOLFIRINOX followed by nabPGem or vice versa. There was no significant difference in OS or PFS for either of the two sequences (p = 0.9). The OS for FOLFIRINOX followed by nabPGem or nabPGem followed by FOLFIRINOX was 13.7 months (95% CI: 12.6-14.7) and 13.8 months (95% CI: 8.6-19), respectively.
CONCLUSIONS: The sequence FOLFIRINOX followed by nab-Paclitaxel and Gemcitabine or vice versa lead to an equal OS outcome.
Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis.
In Vivo. 2019 Jan-Feb; 33(1):271-276 [PubMed] Free Access to Full Article Related Publications
PATIENTS AND METHODS: Metastatic pancreatic cancer patients (n=321) who started systemic chemotherapy between January 2011 and December 2016 were included and were divided into two groups: group A (2011-2013) and group B (2014-2016). Treatment outcomes were evaluated retrospectively.
RESULTS: Patient characteristics were similar between the two groups except for the rates of distant lymph node metastasis and peritoneal metastasis. The preferred regimens in groups A and B were gemcitabine monotherapy and gemcitabine plus nab-paclitaxel therapy, respectively. The response rates, median progression-free survival, and median overall survival of groups A and B were 7.8% and 28.4% (p<0.01), 3.1 months and 5.4 months (p<0.01), and 6.7 months and 10.2 months (p<0.01), respectively.
CONCLUSION: Overall treatment outcomes for metastatic pancreatic cancer were significantly improved after introduction of FOLFIRINOX and gemcitabine plus nab-paclitaxel combination therapy in daily practice.
FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer.
N Engl J Med. 2018; 379(25):2395-2406 [PubMed] Related Publications
METHODS: We randomly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive a modified FOLFIRINOX regimen (oxaliplatin [85 mg per square meter of body-surface area], irinotecan [180 mg per square meter, reduced to 150 mg per square meter after a protocol-specified safety analysis], leucovorin [400 mg per square meter], and fluorouracil [2400 mg per square meter] every 2 weeks) or gemcitabine (1000 mg per square meter on days 1, 8, and 15 every 4 weeks) for 24 weeks. The primary end point was disease-free survival. Secondary end points included overall survival and safety.
RESULTS: At a median follow-up of 33.6 months, the median disease-free survival was 21.6 months in the modified-FOLFIRINOX group and 12.8 months in the gemcitabine group (stratified hazard ratio for cancer-related event, second cancer, or death, 0.58; 95% confidence interval [CI], 0.46 to 0.73; P<0.001). The disease-free survival rate at 3 years was 39.7% in the modified-FOLFIRINOX group and 21.4% in the gemcitabine group. The median overall survival was 54.4 months in the modified-FOLFIRINOX group and 35.0 months in the gemcitabine group (stratified hazard ratio for death, 0.64; 95% CI, 0.48 to 0.86; P=0.003). The overall survival rate at 3 years was 63.4% in the modified-FOLFIRINOX group and 48.6% in the gemcitabine group. Adverse events of grade 3 or 4 occurred in 75.9% of the patients in the modified-FOLFIRINOX group and in 52.9% of those in the gemcitabine group. One patient in the gemcitabine group died from toxic effects (interstitial pneumonitis).
CONCLUSIONS: Adjuvant therapy with a modified FOLFIRINOX regimen led to significantly longer survival than gemcitabine among patients with resected pancreatic cancer, at the expense of a higher incidence of toxic effects. (Funded by R&D Unicancer and others; ClinicalTrials.gov number, NCT01526135 ; EudraCT number, 2011-002026-52 .).
Clinical outcomes of FOLFIRINOX in locally advanced pancreatic cancer: A single center experience.
Medicine (Baltimore). 2018; 97(50):e13592 [PubMed] Free Access to Full Article Related Publications
Meta-analysis of FOLFIRINOX regimen as the first-line chemotherapy for locally advanced pancreatic cancer and borderline resectable pancreatic cancer.
Clin Exp Med. 2019; 19(1):149-157 [PubMed] Related Publications
Galactosylated Chitosan-Functionalized Mesoporous Silica Nanoparticle Loading by Calcium Leucovorin for Colon Cancer Cell-Targeted Drug Delivery.
Molecules. 2018; 23(12) [PubMed] Free Access to Full Article Related Publications
Sarcopenia is a reliable prognostic factor in patients with advanced pancreatic cancer receiving FOLFIRINOX chemotherapy.
Pancreatology. 2019; 19(1):127-135 [PubMed] Related Publications
METHODS: Clinical data of consecutive patients treated with FOLFIRINOX at our institution from 2011 to 2017 was retrospectively reviewed. Skeletal muscle index (SMI) and adipose tissue index (ATI) at the third lumbar spine level was calculated from computed tomography (CT) images. The association between clinical factors (SMI and ATI), and OS and TTF were determined using univariate and multivariate analyses.
RESULTS: We assessed 82 patients. The median OS of sarcopenia and the non-sarcopenia patients were 11.3 and 17.0 months, respectively (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.43-4.32; p = 0.001). Median TTF was 3.0 and 6.1 months in the sarcopenia and the non-sarcopenia patients, respectively (HR, 1.67; 95% CI, 1.03-2.71; p = 0.032). Multivariate analyses revealed that sarcopenia (HR, 1.37; 95% CI, 1.01-1.87; p = 0.045) was an independent prognostic factor of OS. High ATI (p = 0.022) and sarcopenic obesity (p = 0.008) were significantly associated with hematologic toxicity.
CONCLUSIONS: Sarcopenia is an independent indicator of poor prognosis in patients with pancreatic cancer who received FOLFIRINOX, while ATI and sarcopenic obesity predicted severe hematologic toxicity.
Impact of UGT1A1 genetic polymorphism on toxicity in unresectable pancreatic cancer patients undergoing FOLFIRINOX.
Cancer Sci. 2019; 110(2):707-716 [PubMed] Free Access to Full Article Related Publications
Novel models for prediction of benefit and toxicity with FOLFIRINOX treatment of pancreatic cancer using clinically available parameters.
PLoS One. 2018; 13(11):e0206688 [PubMed] Free Access to Full Article Related Publications
METHODS: This retrospective study includes 123 patients with metastatic PC that were treated with FOLFIRINOX between the years 2007 to 2016 in a single academic institution. Survival rates were analysed using the Kaplan-Meier method. Prognostic models including laboratory and clinical parameters were calculated using Cox proportional models in univariate and multivariate analyses.
RESULTS: Median age at diagnosis was 64 years (47-78 years), 71 (57, 7%) were male and the majority had an ECOG performance status of 0 or 1 (63 patients; 83.7%). After a median follow up of 17.8 months, median progression free survival (PFS) and overall survival (OS) were 5.7 (4.55-6.84; 95%CI) and 11.8 months (9.35-14.24; 95%CI) respectively. Overall response rate with FOLFIRINOX was 34.9% and stable disease rate was 21.9%. Regarding Grade 3/4 side effects, 62 events, were reported in 37 patients. Looking at risk factors e.g. patient characteristics, tumor marker, inflammatory markers and body composition multivariate analyses proved CEA >4 elevation and BMI > 25 at the time point before palliative chemotherapy to be independent negative prognostic factors for OS. Grouping patients with no risk factor, one or two of these risk factors we analyzed a median OS of 17.4 moths, 9.6 months and 6.7 months (p<0.001) respectively. In addition we identified thrombocytosis and low BMI as predictors of early toxicity.
CONCLUSION: This study identifies two easily available factors influencing overall survival with FOLFIRINOX therapy. By combining these two factors to create a score for OS, we propose a prognostic tool for physicians to identify patients, who are unlikely to benefit more from FOLFIRINOX or likely to experience toxicity.
Relationship between folate concentration and expression of folate-associated genes in tissue and plasma after intraoperative administration of leucovorin in patients with colorectal cancer.
Cancer Chemother Pharmacol. 2018; 82(6):987-997 [PubMed] Free Access to Full Article Related Publications
METHODS: Eighty patients were randomized into four groups to receive 0, 60, 200, or 500 mg/m
RESULTS: The folate concentration in tumour increased with increasing dosage of LV. Half of the patients treated with 60 mg/m
CONCLUSIONS: The results indicate the possibility of using the individual plasma 5-MTHF/LV ratio after LV injection as a surrogate marker for tissue folate concentration. Expression of several folate-associated genes is associated with folate concentration in tissue and plasma and may become useful when predicting response to LV treatment.
Neoadjuvant FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer: An intention to treat analysis.
Eur J Surg Oncol. 2018; 44(10):1619-1623 [PubMed] Related Publications
METHODS: Patients receiving neoadjuvant FOLFIRINOX for LAPC and BRPC treated between 2014 and 2017 were identified. Post-treatment patients achieving resectability were referred for surgery, whereas unresectable patients continued chemotherapy. Clinical and pathological data were retrospectively compared with control group consisting of 47 consecutive patients with BRPC undergoing pancreatic and portal vein resection between 2008 and 2017.
RESULTS: Thirty LAPC and 23 BRPC patients were identified. Reasons for unresectability included disease progression (70%), locally unresectable disease (18%), and poor performance status (11%). Three patients (10%) with LAPC, and 20 (87%) with BRPC underwent curative surgery. Compared with control group, perioperative complication rate (4.3% versus 28.9%, p = 0.016), and pancreatic fistula rate (0 versus 14.8%, p = 0.08) were lower. Peripancreatic fat invasion (52.2% vs 97.8%, p = 0.001), lymph node involvement (22% vs 54.3%, p = 0.01), and surgical margin involvement (0 vs 17.4%, p = 0.04) were higher in the control group. Median survival was 34.3 months in BRPC patients operated after FOLFIRINOX and 26.1 months in the control group (p = 0.07). Three patients (13%) with complete pathological response are disease-free after mean follow-up of 19 months.
CONCLUSIONS: Whereas neoadjuvant FOLFIRINOX rarely achieves resectability in patients with LAPC (10%), most BRPC undergo resection (87%). Neoadjuvant FOLFIRINOX leads to complete pathological response in 13% of cases, tumor downstaging, and a trend towards improved survival compared with patients undergoing up-front surgery.
Protocol digest of randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan clinical oncology group study (JCOG1407).
Pancreatology. 2018; 18(7):841-845 [PubMed] Related Publications
Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study).
BMC Cancer. 2018; 18(1):762 [PubMed] Free Access to Full Article Related Publications
METHODS: PANACHE01-PRODIGE48 is a prospective multicentre controlled randomized non comparative Phase II trial, evaluating the safety and efficacy of two regimens of neo-adjuvant chemotherapy (4 cycles of mFOLFIRINOX or FOLFOX) relative to the current reference treatment (surgery and then adjuvant chemotherapy) in patients with resectable PDAC. The main co-primary endpoints are OS rate at 12 months and the rate of patients undergoing the full therapeutic sequence.
DISCUSSION: The "ideal" cancer treatment for resectable PDAC would have the following characteristics: administration to the highest possible proportion of patients, ability to identify fast-progressing patients (i.e. poor candidates for surgery), a low rate of R1 resections (through optimisation of local disease control), and an acceptable toxicity profile. The neoadjuvant approach may meet all these criteria. With respect to published data on the efficacy of FOLFOX and mFOLFIRINOX, these two regimens are potential candidates for neoadjuvant use in the aim to optimising oncological outcomes in resectable PDAC.
TRIAL REGISTRATION: ClinicalTrials.gov , NCT02959879 . Trial registration date: November 9, 2016.
Phase I/II Study of Preoperative Chemoradiotherapy With TEGAFIRI for Locally Advanced Rectal Cancer.
Clin Colorectal Cancer. 2018; 17(3):240-246 [PubMed] Related Publications
PATIENTS AND METHODS: A total of 22 patients with locally advanced lower rectal adenocarcinoma were enrolled in the present study. The radiation dose was 50.4 Gy in 28 fractions. UFT (300 mg/m
RESULTS: Dose-limiting toxicity was not observed at any dosing level. The most frequent adverse event was leukopenia (50%), followed by diarrhea (45.5%), anal pain (31.8%), and neutropenia (27.3%). All were well-managed with the appropriate drugs. The total pathologic complete response rate was 22.7%, and the proportion of good responders was 28.6%, 50%, and 71.4% at levels 1, 2, and 3, respectively. None of the patients experienced local recurrence. The 5-year relapse-free and overall survival rates were 80.4% and 80.8%, respectively.
CONCLUSION: TEGAFIRI is a promising CRT regimen that results in marked tumor regression and good local control. Moreover, its adverse events are well-tolerated.
Orthotopic and heterotopic murine models of pancreatic cancer and their different responses to FOLFIRINOX chemotherapy.
Dis Model Mech. 2018; 11(7) [PubMed] Free Access to Full Article Related Publications
Enhancement of 5-Fluorouracil Cytotoxicity by Pyridoxal 5'-Phosphate and Folinic Acid in Tandem.
J Pharmacol Exp Ther. 2018; 366(2):238-243 [PubMed] Related Publications
A phase II trial of gemcitabine, S-1 and LV combination (GSL) neoadjuvant chemotherapy for patients with borderline resectable and locally advanced pancreatic cancer.
Med Oncol. 2018; 35(7):100 [PubMed] Related Publications
Improving the safety of high-dose methotrexate for children with hematologic cancers in settings without access to MTX levels using extended hydration and additional leucovorin.
Pediatr Blood Cancer. 2018; 65(12):e27241 [PubMed] Related Publications
METHODS: The prospective study was conducted at a single centre in Chandigarh, India in 2015. Patients with B-cell acute lymphoblastic leukemia (ALL) or with T-cell ALL or non-Hodgkin lymphoma (T-NHL) were administered 3 and 5 gm/m
RESULTS: The study included 100 cycles of HD-MTX in 53 patients: B-ALL 25 patients (51 cycles), T-ALL 16 patients (28 cycles), T-NHL 10 patients (18 cycles), and relapsed ALL 2 patients (3 cycles). The mean age was 6.8 ± 3.2 years. Patients were underweight in 15 (15%) cycles. Patients in 23% of cycles had a rise in creatinine to >1.25 times the baseline. Toxicities (NCI CTCAE v4.0) included mucositis (32%), diarrhoea (10%), and febrile neutropenia (9%). One patient died from dengue shock syndrome.
CONCLUSIONS: It is safe to administer 3 or 5 gm/m
Surgery after FOLFIRINOX treatment for locally advanced and borderline resectable pancreatic cancer: increase in tumour attenuation on CT correlates with R0 resection.
Eur Radiol. 2018; 28(10):4265-4273 [PubMed] Related Publications
METHODS: Patients with either locally advanced (LA) and borderline resectable (BR) PDAC undergoing surgical exploration after FOLFIRINOX were retrospectively enrolled. Two pancreatic radiologists reviewed the CT blinded to the final outcome and assessed chemotherapy response and resectability. Patients were then divided into R0 resected (group A) and not resected/R1 resected (group B), which were compared.
RESULTS: Of 59 patients included, 19 were defined as unresectable (32%), 33 borderline resectable (56%) and 7 resectable (12%) during the blind radiological evaluation after FOLFIRINOX. Once in a surgical setting, 27% were non-resectable, whereas 73% received surgical resection with a 70% R0 rate. Consequent sensitivity and specificity were 86% and 29%. At imaging review, significant decreases in longest tumour dimension were observed in both groups: from 32 mm (95% CI 15-55) to 21 (10-44) in group A and from 34 (18-70) to 26 (7-60) in group B, p < 0.05. However, a significant increase in tumour attenuation in all phases was only observed for R0 resected, from 52 HU (26-75) to 65 (35-92) in arterial phase (p < 0.001) and from 62 (36-96) to 78 (40-120) in the venous (p = 0.001).
CONCLUSION: After neoadjuvant FOLFIRINOX, CT predicted resectability with acceptable sensitivity but low specificity. The observation of increased tumour attenuation at CT scan after FOLFIRINOX treatment might represent a reliable predictor of R0 resection.
KEY POINTS: • CT drives the assessment of PDAC resectability after FOLFIRINOX • CT predicts resectability with acceptable sensitivity but low specificity • Significant increase in tumour attenuation was only observed for R0 resected PDAC • Tumour attenuation after FOLFIRINOX represents a reliable predictor of R0 resection.
A phase II study of modified FOLFIRINOX for chemotherapy-naïve patients with metastatic pancreatic cancer.
Cancer Chemother Pharmacol. 2018; 81(6):1017-1023 [PubMed] Related Publications
METHODS: Patients with untreated metastatic pancreatic cancer (MPC) received modified FOLFIRINOX (intravenous oxaliplatin 85 mg/m
RESULTS: Sixty-nine pts. were enrolled from 39 institutions in Japan. The median overall survival was 11.2 months [95% confidence interval (CI) 9.0-]. The median progression-free survival was 5.5 months (95% CI 4.1-6.7). The response rate was 37.7% (95% CI 26.3-50.2), and the disease control rate was 78.3% (95% CI 66.7-87.3). The incidence of grade 3 or higher neutropenia was 47.8%. Serious adverse events occurred in six patients (8.7%). All AE proportions were less than those in the previous Japanese full-dose phase II study. One patient died due to interstitial pneumonia related to treatment.
CONCLUSION: This is the first prospective study of modified FOLFIRINOX in Asia. Modified FOLFIRINOX in this study has an improved safety profile with maintained efficacy in MPC without prophylactic pegfilgrastim.
Efficacy and Tolerability of Second-line Nab-paclitaxel and Gemcitabine After Failure of First-line FOLFIRINOX for Advanced Pancreas Cancer: A Single-institution Experience.
Clin Colorectal Cancer. 2018; 17(3):e451-e456 [PubMed] Related Publications
PATIENTS AND METHODS: Patients in whom APC was diagnosed from 2012 to 2016 who underwent chemotherapy at CancerCare Manitoba were identified from the Manitoba Cancer Registry. Pharmacy records were used to identified those patients who had received first-line FOLFIRINOX, followed by second-line NG, GEM alone, or best supportive care. A retrospective analysis was performed to identify the patient and treatment characteristics, toxicity, radiologic response, and survival. Edmonton Symptom Assessment System, revised, scores were analyzed to assess symptom control.
RESULTS: A total of 146 patients had received first-line FOLFIRINOX. Of those with disease progression who were offered second-line therapy, 30 received NG, 8 GEM alone, and 22 best supportive care. NG was more toxic than GEM alone; however, the dose intensity was similar between the 2 groups. The median progression-free survival was 3.61 months in the NG group and 2.51 months in the GEM-alone group. The median overall survival was 5.69 months in the NG group and 3.82 months in the GEM-alone group. No significant differences were found in the Edmonton Symptom Assessment System, revised, scores when stratified by the treatment received.
CONCLUSION: For select patients with APC in whom first-line FOLFIRINOX fails, a role might exist for second-line NG. In our institution, second-line NG was associated with improvement in survival compared with second-line GEM alone, with a manageable toxicity profile.
Nab-paclitaxel plus gemcitabine versus FOLFIRINOX as the first-line chemotherapy for patients with metastatic pancreatic cancer: retrospective analysis.
Invest New Drugs. 2018; 36(4):732-741 [PubMed] Related Publications
Meta-analysis of Modified FOLFIRINOX Regimens for Patients With Metastatic Pancreatic Cancer.
Clin Colorectal Cancer. 2018; 17(3):187-197 [PubMed] Related Publications
MATERIALS AND METHODS: We performed a meta-analysis of reported studies in PubMed, Scopus, and Web of Science (1950-2016) in December 2016. The inclusion criteria were randomized trials, prospective or retrospective cohorts, patients with metastatic pancreatic adenocarcinoma, the use of mFIO or FOLFIRINOX (FIO) chemotherapy, and available information for ≥ 1 efficacy endpoint (response rate, progression-free survival, and/or overall survival). The outcomes were compared according to the chemotherapy regimen using a random effects model. We also performed a meta-regression analysis to evaluate the effect of dose reductions on outcomes.
RESULTS: Of 2525 abstracts, 32 were considered eligible. Modifications in the FIO regimen included omission of the 5-fluorouracil bolus and/or dose reductions in infusional 5-fluorouracil, irinotecan, and/or oxaliplatin. mFIO was not associated with inferior response rates (32% vs. 33%; P = .879), lower rates of survival at 11 months (47% vs. 50%; P = .38), or lower 6-month progression-free survival rates (47% vs. 53%; P = .38). The meta-regression of the percentage of dose reduction failed to show any association.
CONCLUSION: The results of the present meta-analysis with a combined sample size of 1461 patients suggest that it is reasonable to consider mFIO regimens for patients with metastatic pancreatic adenocarcinoma.
Impact of formulation on the iontophoretic delivery of the FOLFIRINOX regimen for the treatment of pancreatic cancer.
Cancer Chemother Pharmacol. 2018; 81(6):991-998 [PubMed] Related Publications
METHODS: Three formulations of the FOLFIRINOX regimen (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) were generated at a fixed pH of 6.0 and were referred to as formulation A (single drug solution with all four drugs combined), formulation B (two drug solutions with two drugs per solution), and formulation C (four individual drug solutions). Anodic iontophoresis of the three different formulations was evaluated in orthotopic patient-derived xenografts of pancreatic cancer.
RESULTS: Iontophoretic transport of the FOLFIRINOX drugs was characterized according to organ exposure after a single device treatment in vivo. We report that the co-iontophoresis of two drug solutions, leucovorin + oxaliplatin and 5-fluorouracil + irinotecan, resulted in the highest levels of cytotoxic drugs in the tumor compared to drugs delivered individually or combined into one solution. There was no significant difference in plasma, pancreas, kidney, and liver exposure to the cytotoxic drugs delivered by the three different formulations. In addition, we found that reducing the duration of iontophoretic treatment from 10 to 5 min per solution resulted in a significant decrease in drug concentrations.
CONCLUSIONS: Underlying the difference in drug transport of the formulations was electrolyte concentrations, which includes both active and inactive components. Electrolyte concentrations can hinder or improve drug electro-transport. Overall, balancing electrolyte concentration is needed for optimal electro-transport.
Posterior Reversible Encephalopathy Syndrome after a Variety of Combined Chemotherapies Containing Bevacizumab for Metastatic Colon Cancer.
Intern Med. 2018; 57(16):2403-2407 [PubMed] Free Access to Full Article Related Publications