levoleucovorin and Chemotherapy-Induced-Febrile-Neutropenia

FOLFOXIRI (Fluorouracil, folinate, oxaliplatin, and irinotecan) plus bevacizumab improved progression-free survival (PFS) and overall survival in patients with metastatic colorectal cancer (mCRC), compared with FOLFIRI (fluorouracil, folinate, and irinotecan) plus bevacizumab, but significantly increased the incidences of adverse events. The efficacy and safety profiles of FOLFOXIRI plus bevacizumab in ethnic Asian patients have not been established yet.. This study was an open-label, single-arm, multi-centered phase II prospective clinical trial in patients with mCRC who received FOLFOXIRI plus bevacizumab. The primary endpoint was the PFS rate at 10 months. Secondary endpoints included overall survival, response rate, and safety.. A total of 69 patients received FOLFOXIRI plus bevacizumab as induction therapy and were assessed for efficacy and safety. The PFS rate at 10 months was 75.2% and the median PFS was 13.3 months. Complete response and partial response were achieved in 2 (2.9%) and 47 patients (69.1%), respectively. Grade 3 and 4 adverse events with incidence rates exceeding 20% were neutropenia (72.5%), hypertension (34.8%), leucopenia (33.3%), and febrile neutropenia (21.7%). Significantly more patients with grade 4 neutropenia had single-heterozygous UGT1A1*1/*6 or *1/*28 (46.2%) than UGT1A1 wild-type genotype (*1/*1) (13.3%) (P = .004).. FOLFOXIRI plus bevacizumab is considered an effective first-line regimen that improves the outcome of patients with mCRC regardless of ethnicity. In Asian patients, utmost attention should be paid to the possible onset of severe neutropenia or febrile neutropenia attributed to different types of UGT1A1*6 and *28 polymorphism, when FOLFOXIRI plus bevacizumab is administered.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asian People; Bevacizumab; Camptothecin; Chemotherapy-Induced Febrile Neutropenia; Colorectal Neoplasms; Female; Fluorouracil; Glucuronosyltransferase; Humans; Induction Chemotherapy; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Progression-Free Survival

In Ontario, FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GnP) have been publicly funded for first-line unresectable locally advanced pancreatic cancer (uLAPC) or metastatic pancreatic cancer (mPC) since April 2015. We examined the real-world effectiveness and safety of FFX vs GnP for advanced pancreatic cancer, and in uLAPC and mPC.. Patients receiving first-line FFX or GnP from April 2015 to March 2017 were identified in the New Drug Funding Program database. Baseline characteristics and outcomes were obtained through the Ontario Cancer Registry and other population-based databases. Overall survival (OS) was assessed using Kaplan-Meier and weighted Cox proportional hazard models, weighted by the inverse propensity score adjusting for baseline characteristics. Weighted odds ratio (OR) for hospitalization and emergency department visits (EDV) were estimated from weighted logistic regression models.. For 1130 patients (632 FFX, 498 GnP), crude median OS was 9.6 and 6.1 months for FFX and GnP, respectively. Weighted OS was improved for FFX vs GnP (HR = 0.77, 0.70-0.85). Less frequent EDV and hospitalization were observed in FFX (EDV: 67.8%; Hospitalization: 49.2%) than GnP (EDV: 77.7%; Hospitalization: 59.3%). More frequent febrile neutropenia-related hospitalization was observed in FFX (5.8%) than GnP (3.3%). Risk of EDV and hospitalization were significantly lower for FFX vs GnP (EDV: OR = 0.68, P = .0001; Hospitalization: OR = 0.76, P = .002), whereas the risk of febrile neutropenia-related hospitalization was significantly higher (OR = 2.12, P = .001). Outcomes for uLAPC and mPC were similar.. In the real world, FFX had longer OS, less frequent all-cause EDV and all-cause hospitalization, but more febrile neutropenia-related hospitalization compared to GnP.

Topics: Aged; Albumins; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Deoxycytidine; Emergency Service, Hospital; Female; Fluorouracil; Follow-Up Studies; Gemcitabine; Hospitalization; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Ontario; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Propensity Score; Treatment Outcome

To evaluate the impact of sex on toxicity and efficacy outcomes among patients with metastatic colorectal cancer receiving first-line 5-fluorouracil-based regimens.. A pooled analysis of data sets from 5 clinical trials (NCT00115765, NCT00364013, NCT00272051, NCT00305188, NCT00384176) was performed. Kaplan-Meier analysis and log-rank testing were used to assess the differences in overall and progression-free survival between male and female subjects. Chi-square testing was used to examine the differences in the incidence of different toxicities between male and female subjects. Multivariate logistic regression analysis (adjusted for age, body mass index, Eastern Cooperative Oncology Group performance status, race, bevacizumab-containing treatment, and panitumumab-containing treatment) was further utilized to assess the impact of gender on different toxicities. Most of the patients were treated with FOLFOX (folinic acid, fluorouracil, and oxaliplatin)-based regimens.. A total of 3223 participants were included in the pooled cohort, among which were 1925 male and 1298 female subjects. Kaplan-Meier survival analysis and log-rank testing were utilized to compare overall and progression-free survival outcomes between male and female subjects. For both end points, there was no difference between male and female subjects (P = .884; P = .647, respectively). Comparing female to male subjects, female subjects were more likely to experience alopecia (20% vs. 8.6%; P < .001), all-grade diarrhea (60.3% vs. 56.7%; P = .039), all-grade nausea and vomiting (68.7% vs. 56.6%; P < .001), high-grade nausea and vomiting (7.1% vs. 4.5%; P = .002), all-grade anemia (19.6% vs. 14.2%; P < .001), all-grade neutropenia (51.1% vs. 36.6%; P < .001), and high-grade neutropenia (37.1% vs. 24.1%; P < .001). These differences were further confirmed in multivariate logistic regression analyses.. Female subjects with metastatic colorectal cancer receiving first-line chemotherapy demonstrated higher rates of a number of toxicities (essentially hematologic and gastrointestinal in nature). Additional studies into the differential effect of systemic therapy on female versus male subjects are needed.

Topics: Aged; Alopecia; Anemia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Colorectal Neoplasms; Female; Fluorouracil; Humans; Incidence; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Nausea; Organoplatinum Compounds; Progression-Free Survival; Randomized Controlled Trials as Topic; Sex Factors; Vomiting

Our objective was to evaluate the benefit of re-exposing patients with refractory metastatic colorectal cancer (mCRC) to a combination of oxaliplatin, irinotecan and 5-fluorouracil treatment.. We retrospectively analysed patients with mCRC who received a combination of oxaliplatin, irinotecan and fluorouracil as a rechallenge regimen after progressing on the same drugs. Both FOLFOXIRI and FOLFIRINOX were used. Toxicity was evaluated for each treatment cycle, and survival analysis was performed using the Kaplan-Meier method.. A total of 21 patients who were treated between January 2011 and December 2013 were selected for this study. Most of the patients (95.2%) had an ECOG status of 0-1. The median age at diagnosis was 52.1 years (range 36-77 years), and 14 (66.6%) patients had wild-type KRAS. Thirteen patients received FOLFIRINOX, and eight received FOLFOXIRI. Most patients had previously received at least three regimens, with 80% receiving anti-VEGF and 66% anti-EGFR antibodies. The response rate was 38%, and 24% patients had stable disease. The median time to disease progression was 4.0 months (range 1.0-9.1 months), and the median overall survival duration was 8.6 months (range 6.3-11.5 months). Most patients required dose adjustment and treatment delays. One patient experienced grade 5 neutropenic sepsis.. Both FOLFIRINOX and FOLFOXIRI are active and potentially feasible rechallenge treatment options for heavily pretreated patients with good performance status. With dose reduction and close monitoring for toxicity, the risk of serious adverse events can be minimised.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy-Induced Febrile Neutropenia; Colorectal Neoplasms; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organometallic Compounds; Organoplatinum Compounds; Oxaliplatin; Retreatment; Retrospective Studies; Treatment Outcome

FOLFIRINOX has increased efficacy but also toxicity. Despite various modified FOLFIRINOX regimens, how much reduction is acceptable remains unclear. This study aimed to find the optimal relative dose intensity (RDI, %) of FOLFIRINOX that preserves tumour responses in patients with advanced pancreatic cancer (PC).. We reviewed 201 patients with PC treated with first-line FOLFIRINOX during 2012-2015. We established a modified Hryniuk model (http://www.rdicalc.com) and defined cumulative RDI (cRDI, %). The optimal cRDI thresholds for response rate (RR) and disease control rate (DCR) were assessed using receiver operating characteristic (ROC) analysis. Relationships between cRDI and haematologic toxicities (neutropenia and febrile neutropenia [FN]) were also analysed according to use of granulocyte colony-stimulating factor (G-CSF).. Among 156 eligible patients, 133 (48 locally advanced PC and 85 metastatic PC) completed initial treatment plan prior to the first radiological evaluation (median 58 days; 71.8% cRDI). For optimal cRDI thresholds, ROC curves showed a 71.2% cRDI for RR (83.3% sensitivity, 64.7% specificity, and 0.746 area under the curve [AUC]) and a 55.3% cRDI for DCR (93.6% sensitivity, 62.5% specificity and 0.805 AUC). Among 96 patients who did not receive prophylactic G-CSF, cRDI ≥80.1% was a significant predictor for frequent FN (73.7% sensitivity, 72.7% specificity and 0.793 AUC). There was no correlation between cRDI and haematologic toxicities in patients receiving prophylactic G-CSF.. To preserve optimal RR and DCR in advanced PC, cRDI values for FOLFIRINOX >70% and >55%, respectively, are recommended. If cRDI is >80%, primary G-CSF prophylaxis is needed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Pancreatic Ductal; Chemotherapy-Induced Febrile Neutropenia; Dose-Response Relationship, Drug; Female; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms

How does giving adjuvant FOLFOX chemotherapy to patients with early-stage colorectal cancer (ESCRC) regardless of the day-before absolute neutrophil counts (ANC) effect chemotherapy-induced febrile neutropenia (CIFN) rates, received dose intensity (RDI), and chemotherapy cycle delay? Does an ANC level predict future neutropenia?. A retrospective chart review was conducted on all patients receiving adjuvant chemotherapy for ESCRC at a mid-sized community hospital in Toronto, Ontario, Canada between April 2005 and May 2014. All patients were under one medical oncologist. Day-before CBC data were collected along with other patient characteristics. CIFN was confirmed by hospital records. Inclusion criteria were met by 132 patients. Overall, 1074 cycles of chemotherapy were analyzed.. Six episodes of CIFN were observed. There was a significant difference in the average day-before ANC between patients who developed CIFN (1.4 × 10(9)/L, 95 % CI 0.76-2.0 × 10(9)/L) and those who did not (2.9 × 10(9)/L, 95 % CI 2.8-3.0 × 10(9)/L, p = 0.03). The RDI for oxaliplatin was 0.95 and for 5-fluorouracil (5-FU) was 0.96. A total of 170 cycles were given at day-before ANC <1.5 × 10(9)/L (range 0.1 × 10(9)/L-1.4 × 10(9)/L), and 24 were delayed for 1 week for hematologic reasons. Cycles given with grade 2 neutropenia predicted higher grades of neutropenia with a sensitivity of 0.22 (95 % CI 0.12-0.38).. Adjuvant FOLFOX chemotherapy may be given in the setting of low day-before ANC to patients with ESCRC. The benefits include higher RDI and a reduced number of clinic visits for the patient.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Chemotherapy, Adjuvant; Colorectal Neoplasms; Female; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Leukocyte Count; Male; Middle Aged; Organoplatinum Compounds; Retrospective Studies