levoleucovorin and Febrile-Neutropenia

TRIBE and TRIBE-2 studies demonstrated higher benefit from FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan)/bevacizumab compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) or FOLFOX/bevacizumab as an upfront option for metastatic colorectal cancer patients, with more toxicities. We focused on the incidence and longitudinal dynamics of neutropenia and febrile neutropenia (FN) in the two studies, to evaluate their clinical relevance, the magnitude of impact of FOLFOXIRI/bevacizumab, and the role of risk factors in predicting their occurrence.. The overall incidence of grade 3-4 (G3-4) neutropenia and FN, the time to their onset, the use of granulocyte colony-stimulating factor, and the association with risk factors were evaluated in the overall population and according to treatment arm. FN episodes were assessed by Multinational Association for Supportive Care in Cancer (MASCC) score.. Among 1155 patients, 568 (49%) received FOLFOXIRI/bevacizumab. Overall, 410 (35%) experienced G3-4 neutropenia and 70 (6%) FN, 21 (2%) at high risk. FOLFOXIRI/bevacizumab was associated with higher incidence of neutropenia (51% versus 21%, P < 0.001), FN (8% versus 4%, P = 0.02), and high-risk FN [18 (3%) versus 3 (1%), P = 0.015]. No related deaths were observed. The first episode of G3-4 neutropenia and FN occurred mainly in the first 2 months in both arms. Longitudinal analysis showed different patterns of evolution over cycles between the arms (P < 0.001) G3-4 neutropenia being more frequent in the first cycles with FOLFOXIRI/bevacizumab. Older patients (P = 0.01) and females (P < 0.001) had a significantly higher risk of G3-4 neutropenia. No significant interaction effect between arm and analysed risk factors in terms of risk of G3-4 neutropenia or FN was observed. The incidence of FN among older females receiving FOLFOXIRI/bevacizumab was 12%. Neither G3-4 neutropenia nor FN impaired efficacy in terms of overall response rate, progression-free survival, and overall survival.. FOLFOXIRI/bevacizumab has a higher risk of G3-4 neutropenia and FN than doublets/bevacizumab. FN occurred in <10% of patients, mostly as low-risk episodes. A closer monitoring during the first 2 months is recommended; prophylactic use of granulocyte colony-stimulating factor may be considered for older females.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Febrile Neutropenia; Female; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds

Pegfilgrastim's role in reducing the risk of febrile neutropenia (FN) in patients with colorectal cancer (CRC) receiving chemotherapy plus bevacizumab was not previously evaluated in a prospective study. The present phase III, double-blind trial evaluated the efficacy of pegfilgrastim versus placebo in reducing the incidence of grade 3/4 FN in patients with advanced CRC receiving bevacizumab combined with first-line chemotherapy (FOLFOX [leucovorin, 5-fluorouracil, oxaliplatin] or FOLFIRI [leucovorin, 5-fluorouracil, irinotecan]).. Patients aged ≥ 18 years with locally advanced or metastatic CRC were randomized 1:1 to placebo or 6 mg of pegfilgrastim ∼24 hours after receiving chemotherapy plus bevacizumab every 14 days. The study treatment period included 4 cycles, but patients could continue treatment for ≤ 60 months. The primary endpoint was incidence of grade 3/4 FN in the first 4 cycles. The secondary endpoints included the objective response rate (ORR), overall survival, and progression-free survival, analyzed at the end of the long-term follow-up period.. A total of 845 patients were randomized from November 2009 to January 2012 (422, pegfilgrastim; 423, placebo). Pegfilgrastim significantly reduced the incidence of grade 3/4 FN in the first 4 treatment cycles (pegfilgrastim, 2.4%; 95% confidence interval [CI], 1.1%-4.3%; placebo, 5.7%; 95% CI, 3.7%-8.3%; odds ratio [OR], 0.41; P = .014). No significant differences were observed between the 2 arms in ORR (OR, 1.15; P = .330), overall survival (hazard ratio, 0.94; P = .440), and progression-free survival (hazard ratio, 0.93; P = .300).. Pegfilgrastim reduced the FN incidence in patients with advanced CRC receiving chemotherapy and bevacizumab. Administration of pegfilgrastim was tolerable and did not negatively affect the tumor response or survival in this patient population.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Double-Blind Method; Febrile Neutropenia; Female; Filgrastim; Fluorouracil; Follow-Up Studies; Humans; Incidence; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Polyethylene Glycols; Proportional Hazards Models; Prospective Studies; Survival Rate; Vascular Endothelial Growth Factor A; Young Adult

FOLFIRINOX is the standard therapy in patients with unresectable pancreatic cancer (PC). However, FOLFIRINOX frequently induces febrile neutropenia (FN) and neutropenia. The purpose of this study was to explore risk factors for FN and grade 4 neutropenia (NP G4) in patients receiving FOLFIRINOX for PC.. We collected data on 106 patients with PC treated with first-line FOLFIRINOX between 2015 and 2017 using the Pancreatic Cancer Cohort Registry of Severance Hospital in Seoul, Korea.. Multivariate logistic regression analysis showed that female (OR, 3.24; P = 0.023), Eastern Cooperative Oncology Group performance status (OR, 3.70; P = 0.024), overweight (OR, 4.25; P = 0.022), and initial biliary stent insertion (OR, 4.22; P = 0.008) were significantly related to a high risk of FN. Time-dependent bias was reduced using Cox regression analysis, which revealed that female (OR, 2.29; P = 0.041), overweight (OR, 2.67; P = 0.022), and initial biliary stent insertion (OR, 2.59; P = 0.016) were statistically significant predictors. Regarding NP G4, female sex (OR, 2.90; P = 0.016) and overweight (OR, 4.07; P = 0.033) were identified as risk factors in multivariate analysis; however, in Cox regression analysis, tumor in the head of the pancreas (OR, 1.96; P = 0.027) and hemoglobin (g/dL < 12) (OR, 1.87; P = 0.049) were also identified as risk factors.. Female sex, overweight, and initial biliary stent insertion were independent risk factors for the occurrence of FN in patients with unresectable PC treated with FOLFIRINOX.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Factor Analysis, Statistical; Febrile Neutropenia; Female; Fluorouracil; Follow-Up Studies; Humans; Incidence; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Oxaliplatin; Pancreatic Neoplasms; Prognosis; Republic of Korea; Retrospective Studies; Risk Factors; Survival Rate

By using the Korean Pancreatic Cancer (K-PaC) registry, we compared the clinical outcomes of FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GNP) in patients with metastatic pancreatic cancer (MPC).. We constructed a web-based database of 3748 anonymized patients diagnosed with pancreatic ductal adenocarcinoma. MPC patients who received first-line FFX or GNP were enrolled. Overall survival (OS), progression-free survival, grade III to IV toxicity, and cross-over treatment were analyzed.. A total of 413 patients (232 vs. 181, FFX vs. GNP; all data are presented in this sequence) were eligible. Median age was 63 years (60 vs. 69 y) with 43% (39% vs. 47%) comprising female individuals. The major metastatic sites were the liver (64%), peritoneum (25%), and distant lymph nodes (18%). The median OS was 11.5 versus 12.7 months (hazard ratio [HR]=0.87, 95% confidence interval [CI]: 0.68-1.12, P=0.286), and median progression-free survival was 7.5 versus 8.1 months (HR=0.92, 95% CI: 0.70-1.20, P=0.517), respectively. The frequency of grade III to IV febrile neutropenia was higher in the FFX group (18% vs. 11%, P=0.040), and that of peripheral neuropathy was higher in the GNP group (8% vs. 14%, P=0.046). The chance to receive second-line chemotherapy was higher in the GNP group (45% vs. 56%, P=0.036). In the cross-over treatment, the median OS of the FFX-GNP group (n=43) and the GNP-FFX group (n=47) was 16.8 versus 17.7 months (HR=0.79, 95% CI: 0.44-1.41, P=0.425).. FFX and GNP showed similar efficacy and comparable toxicity in MPC patients. Although the GNP group had a higher chance to receive second-line chemotherapy, they did not have improved overall survival.

Topics: Aged; Albumins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Cross-Over Studies; Deoxycytidine; Febrile Neutropenia; Female; Fluorouracil; Gemcitabine; Humans; Irinotecan; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Peripheral Nervous System Diseases; Peritoneal Neoplasms; Progression-Free Survival; Registries; Republic of Korea; Survival Rate; Treatment Outcome

Practice patterns of same-day versus next-day pegfilgrastim vary in numerous practice settings across the country. Current utilization with same-day pegfilgrastim reduced overall visits and reduced treatment time for chemotherapy administration.. To assess the efficacy and safety of same-day versus next-day pegfilgrastim in patients with colorectal cancer.. Patient data was extracted through electronic health records (EHR) search of ICD-9 codes that matched patients with CRC and treated with FOLFOX or FOLFIRI from November 2013 to January 2016. The incidence rates of primary and secondary endpoints were estimated for patients who received either FOLFOX or FOLFIRI and same-day pegfilgrastim with 2-sided 95% confidence intervals. Fisher's exact test for 2 × 2 contingency tables was used to compare the incidence of primary and secondary endpoints between the two study groups performed at the α = 0.05 significance level. A study by Hecht et al. served as a historical control for next-day pegfilgrastim.. A total of 109 out of an initial 330 patients with appropriate ICD-9 criteria were eligible for study inclusion. The primary endpoint of incidence of FN recorded over 4 chemotherapy cycles with either FOLFOX6 or FOLFIRI occurred in 3.7% of patients (95% CI, 1.1-9.4%). Secondary endpoints also occurred with a relatively low incidence: 13 patients developed grades 3/4 neutropenia (11.9%; 95% CI, 7.0-19.5%); 11 patients required dose reductions because of neutropenia or FN (10.1%; 95% CI, 5.6-17.3%); and 5 patients were hospitalized due to neutropenia or FN (4.6%; 1.7-10.6%). There were 4 reported events of FN (3.2%; 95% CI, 1.0-8.3%) for those who received next-day pegfilgrastim compared to 11 events in the placebo group (9.4%; 95% CI, 5.1-16.4%). The incidence of dose delays or dose reductions due to neutropenia or FN were 5 (4.1%, 95% CI, 1.5-9.4%) in the next-day pegfilgrastim group versus 26 (22.1%, 95% CI, 15.5-30.4%) in the placebo group.. The study was retrospective in design and utilized a historical control for the comparator.. Our study results suggest that same-day pegfilgrastim administration may be a safe and effective alternative to 24-h post-chemotherapy administration in patients with esophageal, gastric, appendiceal, or colorectal cancer undergoing treatment with FOLFOX or FOLFIRI.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Febrile Neutropenia; Female; Filgrastim; Fluorouracil; Granulocyte Colony-Stimulating Factor; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Organoplatinum Compounds; Polyethylene Glycols; Recombinant Proteins; Retrospective Studies; Treatment Outcome

Acute methotrexate overdose rarely causes systemic toxicity due to saturable absorption and rapid renal elimination. We present a case of methotrexate toxicity following acute overdose.. A 56-year-old female presented soon after an overdose of 1250 mg of methotrexate, zopiclone and tramadol. The methotrexate was initially under-reported (500 mg) and folinic acid was not provided. Despite normal renal function, the patient developed toxicity. She represented 5 days following the overdose with mucositis, bone marrow suppression and prolonged febrile neutropenia. Treatment included folinic acid, broad-spectrum antibiotics, filgrastim, red cell and platelet transfusion. Her bone marrow began to recover 12 days following the overdose. She was discharged home on Day 17.. Severe toxicity following an acute ingestion of a large amount of methotrexate is rarely reported. The development of toxicity was unexpected in this case given methotrexate's pharmacokinetics and the patient's normal renal function. The serum methotrexate concentrations were below the treatment threshold of the folinic acid rescue therapy nomogram suggesting that the nomogram should not be relied on in acute ingestions. Large acute oral methotrexate poisoning can result in systemic toxicity and folinic acid therapy should be provided in ingestions >1000 mg.

Topics: Anti-Bacterial Agents; Antirheumatic Agents; Azabicyclo Compounds; Blood Transfusion; Bone Marrow Diseases; Drug Overdose; Febrile Neutropenia; Female; Filgrastim; Gastrointestinal Diseases; Humans; Leucovorin; Methotrexate; Middle Aged; Mucositis; Piperazines; Suicide, Attempted; Tramadol

Topics: Aged; Anti-Bacterial Agents; Exanthema; Febrile Neutropenia; Female; Folic Acid; Humans; Leucovorin; Methotrexate; Necrosis; Pancytopenia; Rheumatic Fever; Skin; Stomatitis

Gastric cancer is often diagnosed in advanced stage. Palliative chemotherapy or best supportive care is recommended for patients with metastatic gastric patients. In several clinical trials, palliative chemotherapy improved overall survival (OS) and progression-free survival (PFS), but the survival benefit of second-line chemotherapy was demonstrated in small cohort studies. The main aim of our study was to compare retrospectively the efficacy of second-line modified EOX (epirubicin, oxaliplatin and capecitabine) [mEOX] and irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) regimens in metastatic gastric cancer patients that progressed on first-line modified docetaxel-cisplatin-fluorouracil (DCF) regimen. Metastatic gastric cancer patients who progressed on modified DCF regimens were included. A total 105 patients were included to this study; 55 and 50 patients were treated with mEOX and FOLFIRI regimens, respectively. The clinicopathological and demographic characteristics of all patients were collected from the medical charts. Kaplan-Meier survival analysis was carried out for PFS and OS. The median follow-up of our study was 16 (4-85) months. In both groups, all of the patients were treated with first-line mDCF. Median cycle of second-line chemotherapy was 3 (1-8) and 3.5 (1-6) in EOX and FOLFIRI groups, respectively (P = 0.44). Overall response rate was observed in 34.6 % and 42.0 % of patients second-line chemotherapy in mEOX and FOLFIRI arms, respectively (P = 0.17). Median PFS was 5.5 and 6.3 months in mEOX and FOLFIRI arms, respectively (P = 0.98). Median OS was 6.9 and 7.0 months in mEOX and FOLFIRI arms, respectively, from the time of beginning second-line chemotherapy protocol (P = 0.89). As compared with FOLFIRI regimen, mEOX regimen was associated with less neutropenia, thrombocytopenia and anemia. Dose reduction and dose delay were significantly higher in FOLFIRI group compared to mEOX group (P < 0.001). In our trial, triplet regimens mEOX and FOLFIRI regimens have similar efficacy as second-line treatment for patients with metastatic gastric cancer. FOLFIRI regimen was associated with more hematological toxicity.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Febrile Neutropenia; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Retrospective Studies; Stomach Neoplasms; Treatment Outcome