levoleucovorin and Venous-Thromboembolism

A 71-year-old woman was admitted for fever and appetite loss. She was diagnosed with ascending colon cancer, with portal vein tumor thromboembolism extending to the portosplenic junction. This was deemed unresectable despite the absence of distant metastasis. She underwent 16 courses of mFOLFOX6 therapy, and because the effect of chemotherapy was PR, right hemicolectomy with high ligation of the ileocolic vessels and the right branch of the middle colic vessels was performed. The tumor stage was yp-T3N1bM0, StageⅢB with a few remaining cancer cells in the portal venous system. Staging after chemotherapy effect was Grade 1a. Postoperatively, 13 courses of mFOLFOX6 were administered. A repeat CT scan showed lymph node recurrence along the SMV, which was subsequently resected again. After the second operation, 9 courses of the DeGramont regimen was administered and discontinued. Five years after the last operation, the patient remains well and without any recurrences. Colonic carcinoma with portal venous tumor thromboembolism has been reported in 9 cases, including ours. Among these, 8 cases involved the ascending colon. Seven of the affected patients were female while 3 were poorly differentiated adenocarcinoma. None of the other patients, except for our case, reported a 5 year patient survival rate without recurrence.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colectomy; Colon, Ascending; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Lymph Node Excision; Organoplatinum Compounds; Portal Vein; Time Factors; Treatment Outcome; Venous Thromboembolism

Venous thromboembolism associated with use of a central venous access system is an urgent problem in patients treated with bevacizumab (bev). We investigated the effectiveness of Doppler ultrasound imaging (DUS) in the early detection of catheter-related thrombosis for avoidance of severe venous thromboembolism. Patients with metastatic colorectal cancer received either FOLFOX-4 + bev or FOLFIRI + bev. DUS was performed on the deep venous system for detection of thrombus formation during the initial cycle of treatment, followed by re-evaluation after the third cycle in patients with asymptomatic thrombus formation. All patients were followed up until treatment was interrupted. Median duration of follow-up was 484 days (range 72-574). Among 41 enrolled patients, curable symptomatic thrombosis occurred in one, and asymptomatic thrombosis in 21 (51.2%). Of 21 patients undergoing re-evaluation, thrombi remained without progression in 17 patients, and enlargement in 4 patients. In two of the patients in whom there was progression, pulmonary embolism occurred after the sixth cycle. In the asymptomatic group, no thrombi developed as far as the superior vena cava in any patient. In the cases of progression, thrombotic enlargement was observed in all the 4 patients, with decreased vascular flow in 2. Using DUS, we were able to detect asymptomatic thrombosis in the early cycles of treatment, indicating its potential in the monitoring of venous thrombi. In the event of an enlarging asymptomatic thrombosis developing into the superior vena cava along with decreased vascular flow, careful follow-up and appropriate anticoagulant therapy may be recommended without increased risk of bleeding.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Catheterization, Central Venous; Colorectal Neoplasms; Disease Progression; Early Diagnosis; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Prospective Studies; Pulmonary Embolism; Risk Factors; Thrombophilia; Ultrasonography, Doppler; Vena Cava, Superior; Venous Thromboembolism; Young Adult

To investigate the incidence and clinical implications of venous thromboembolism (VTE) in advanced colorectal cancer (ACC) patients treated and followed-up through a prospective randomised trial, comparing FOLFIRI chemotherapy given as an intermittent or as a continuous schedule.. A total of 266 patients were randomised by 15 experimental centres: 168 (63.2%) were males, median age: 64.6 years, age range: 37-76 years. Almost all (95.5%) patients had metastatic disease, while the remainder were classified with locally advanced irresectable disease. For 138 (51.9%) of the patients, the chemotherapy treatment was intermittent FOLFIRI and the remaining patients received continuous treatment. All toxicities, including VTE, were prospectively collected.. During the study protocol, the central data management gathered two cases of VTE. Our analysis retrieved 27 (10.2%) patients who developed a VTE, almost all (89%) during the course of chemotherapy treatment: 20 out of 27 during FOLFIRI, the remaining 7 during following lines or follow-up. VTE was the most frequent grade 3/4 toxicity. The incidence of VTE was significantly increased in the patients receiving continuous rather than intermittent treatment (HR 2.67, 95% CI 1.17-6.10; p<0.02).. VTE is a common complication among advanced colorectal cancer patients and yet this type of toxicity is widely underestimated. In this randomised trial, VTE was the most frequent grade 3/4 toxicity. Use of an intermittent schedule is associated with a reduced risk of developing VTE.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Humans; Incidence; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Prospective Studies; Survival Rate; Venous Thromboembolism

Recent advances in prophylactic anticoagulation and antineoplastic treatment for advanced pancreatic cancer (aPC) warrant an updated reassessment of thromboembolic risk in this population. This multicenter retrospective cohort study aims to comprehensively characterize incidence, risk factors, and outcomes of venous (VTE) and arterial thromboembolism (ATE) in homogenously treated patients with aPC.. Four hundred and fifty-five patients with aPC undergoing palliative first-line chemotherapy (Gemcitabine/nab-Paclitaxel (GN) or FOLIRINOX) were included. Primary outcomes were objectively confirmed VTE and/or ATE.. Patients with aPC undergoing palliative first-line chemotherapy with FOLFIRINOX or GN face a high risk for VTE/ATE and its diagnosis is linked to worse clinical outcomes. VTE-risk prediction models have limited ability to sub-stratify thrombotic events in this high-risk scenario.

Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Fluorouracil; Gemcitabine; Humans; Irinotecan; Leucovorin; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Retrospective Studies; Venous Thromboembolism

A 55-year-old patient with locally advanced pancreatic carcinoma will start Folfirinox. Should he get thromboprophylaxis?. Patients with malignant disease have increased risk of venous thromboembolism (VTE). Several types of malignancy, surgery, chemotherapy and metastasis lead to increased risk. VTE is an underdiagnosed phenomenon and the second cause of death in patients treated with chemotherapy. Therapeutic doses increase the risk of bleeding compared to prophylactic anticoagulant treatment. Even though they are less than perfect, several risk scores are able to identify patients with high risk of VTE. The AVERT and CASSINI trials showed that prophylactic doses of DOACs in cancer patients with high risk of VTE are able to significantly reduce this risk.. Even though there are many unresolved questions, it seems rational to start thromboprophylaxis in patients with aggressive types of cancer, preferably using DOACs, but low molecular weight heparins are possible as well. Risk scores may be helpful when selecting patients.

Topics: Anticoagulants; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemoprevention; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Oxaliplatin; Pancreatic Neoplasms; Risk Adjustment; Risk Assessment; Venous Thromboembolism

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Collateral Circulation; Colorectal Neoplasms; Disease Progression; Enoxaparin; Fatal Outcome; Female; Fibrinolytic Agents; Fluorouracil; Humans; Leucovorin; Middle Aged; Superior Vena Cava Syndrome; Tomography, X-Ray Computed; Venous Thromboembolism

The risk of venous thromboembolism has been reported to increase when receiving bevacizumab. Many cancer patients are reported to have elevated D-dimer levels. It is not clear what D-dimer level might indicate an increased risk of venous thromboembolism in the colorectal cancer patients treated with bevacizumab-containing chemotherapy.. The D-dimer levels and any event concurrent with an elevated D-dimer level were evaluated in patients receiving bevacizumab. The D-dimer cut-off level was determined using the receiver-operating characteristic analysis. The selection criteria were as follows: histologically proven metastatic and unresectable colorectal adenocarcinoma; no prior chemotherapy containing bevacizumab; D-dimer test performed repetitively on the baseline and during bevacizumab administration; no venous thromboembolism identified at the baseline; and enhanced computed tomographic scan performed every 2 months.. Sixty-nine patients were included. The chemotherapy regimens with bevacizumab included the regimen of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), the regimen of 5-fluorouracil, leucovorin and irinotecan (FOLFIRI), and leucovorin-modulated 5-fluorouracil. The median baseline D-dimer level was 1.2 µg/ml. The appropriate D-dimer cut-off level was 3 µg/ml with the negative predictive value of 98% and relative risk of 6.9. Twenty-one of 69 patients showed elevated D-dimer levels of >3 µg/ml, with 11 patients for unknown reasons, 6 with tumor progression, 3 with venous thromboembolism and 1 with sepsis. In the remaining 48 patients whose D-dimer levels were ≤3 µg/ml, only one patient developed a venous thromboembolism.. A D-dimer cut-off level of 3 µg/ml might be a useful indicator level to exclude venous thromboembolism or show an increased risk for venous thromboembolism in colorectal cancer patients treated with bevacizumab-containing chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Disease Progression; Female; Fibrin Fibrinogen Degradation Products; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Retrospective Studies; Sensitivity and Specificity; Sepsis; Venous Thromboembolism

The case of a 16-year-old girl with primary mediastinal large B-cell lymphoma who had thrombosis in the brachiocephalic, subclavian, and internal jugular veins at presentation is reported. MACOP-B chemotherapy plus radiation therapy could be the first-line strategy, but MACOP-B increases the risk of thrombosis. Although an effective method for initial treatment of venous thromboembolism (VTE) in cancer patients has not been established, recent studies revealed that the administration of a low-molecular-weight heparin (LMWH) was effective for secondary prevention of VTE. Therefore, the patient in this case was treated with MACOP-B plus rituximab followed by radiation therapy, and an LMWH was administered through the course of treatment. She achieved complete remission and never suffered from VTE. This case suggests that long-term administration of an LMWH contributes to the primary improvement and secondary prevention of VTE even in patients who are at high risk for thrombosis.

Topics: Adolescent; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Heparin, Low-Molecular-Weight; Humans; Leucovorin; Lymphoma, Large B-Cell, Diffuse; Mediastinal Neoplasms; Methotrexate; Prednisone; Rituximab; Venous Thromboembolism; Vincristine