levoleucovorin and Pulmonary-Embolism

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

The study aimed to demonstrate the noninferiority of capecitabine to 5-fluorouracil (5-FU)/folinic acid (FA), in relation to progression-free survival (PFS) after first-line treatment of metastatic colorectal cancer and the benefit of adding celecoxib (C) to irinotecan/fluoropyrimidine regimens compared with placebo (P).. Patients were randomly assigned to receive FOLFIRI: irinotecan (180 mg/m(2) i.v. on days 1, 15 and 22); FA (200 mg/m(2) i.v. on days 1, 2, 15, 16, 29 and 30); 5-FU (400 mg/m(2) i.v. bolus, then 22-h, 600 mg/m(2) infusion) or CAPIRI: irinotecan (250 mg/m(2) i.v. infusion on days 1 and 22); capecitabine p.o. (1000 mg/m(2) b.i.d. on days 1-15 and 22-36). Patients were additionally randomly assigned to receive either placebo or celecoxib (800 mg: 2 x 200 mg b.i.d.).. The trial was closed following eight deaths unrelated to disease progression in the 85 enrolled (629 planned) patients. Response rates were 22% for CAPIRI + C, 48% for CAPIRI + P, 32% for FOLFIRI + C and 46% for FOLFIRI + P. Median PFS and overall survival (OS) times were shorter for CAPIRI versus FOLFIRI (PFS 5.9 versus 9.6 months and OS 14.8 versus 19.9 months) and celecoxib versus placebo (PFS 6.9 versus 7.8 months and OS 18.3 versus 19.9 months).. Due to the small sample size following early termination, no definitive conclusions can be drawn in relation to the noninferiority of CAPIRI compared with FOLFIRI.

Topics: Adenocarcinoma; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Celecoxib; Colorectal Neoplasms; Cyclooxygenase 2 Inhibitors; Deoxycytidine; Diarrhea; Double-Blind Method; Female; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Leucovorin; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Pyrazoles; Shock, Septic; Sulfonamides; Survival Analysis

In May 2007, a 48-year-old woman was admitted to our hospital for acute intestinal obstruction, and she was subsequently diagnosed with metastatic colorectal cancer in the sigmoid colon. Jejunum-ileum anastomosis and colostomy were performed as palliative surgery because the locally-advanced primary tumor had involved the ileum and other surrounding organs and formed huge mass. After placement of a central venous port, palliative chemotherapy mFOLFOX6 was commenced. In May 2008, mFOLFOX6 was replaced with FOLFIRI because of progression of both the metastasized and the primary tumors. On November 20, 2008, cetuximab was added to FOLFIRI because of the further disease progression. However, on December 24, 2008, the patient presented with sudden-onset dyspnea. Her blood gas analysis revealed severe hypoxemia and metabolic acidosis, and CT scan showed bilateral pulmonary artery embolism. After intensive treatment, the patient was able to walk under the room-air condition. However, on January 19, 2009, she died of pneumonitis. We believe that this is an interesting case with respect to the relationship between pulmonary embolism and malignancy and may hint at a causal relationship between pulmonary embolism and cetuximab, which is currently uncertain. We report this case herein along with a literature review.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Colorectal Neoplasms; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Middle Aged; Palliative Care; Pulmonary Embolism

We report two cases of venous thrombosis confirmed during the bevacizumab combination chemotherapy for colorectal cancer. Case 1 was a 59-year-old man. We performed an operation for cancer of the rectum. At 2 years after the operation, he received mFOLFOX6 + bevacizumab therapy for a recurrence in the pelvis and lungs metastasis. After the 14th courses, He had a right shoulder pain and contrast enhanced computed tomography revealed deep vein thrombosis to the right arms. Case 2 was a 65-year-old man. We performed an operation for cancer of the rectum. At 6 months after the operation, he received mFOLFOX6 + bevacizumab therapy for lung metastases. After the 6th courses, contrast enhanced computed tomography revealed deep venous and pulmonary thrombosis for both sides, pulmonary thrombosis.

Topics: Aged; Angiogenesis Inducing Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Pulmonary Embolism; Rectal Neoplasms; Venous Thrombosis

Topics: Adult; Aged; Antineoplastic Agents; Bilirubin; Biopsy; Catheterization; Female; Fluorouracil; Hepatic Artery; Humans; Leucovorin; Ligation; Liver Function Tests; Liver Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Metastasis; Palliative Care; Pulmonary Embolism