levoleucovorin and Venous-Thrombosis

In our previous randomized controlled trial, the addition of S-1 to gemcitabine for advanced pancreatic cancer did not prolong overall survival (OS) significantly, despite its higher response rate and longer progression-free survival (PFS). Leucovorin is known to enhance efficacy of S-1, and we conducted this phase I trial of combination therapy of gemcitabine, S-1 and leucovorin (GSL).. Patients with advanced pancreatic cancer who had received no prior chemotherapy were eligible for this study. Gemcitabine was administered at an escalating dose of 600, 800 and 1,000 mg/m(2) over 30 min on day 1, and oral S-1 at a dose of 40 mg/m(2) twice daily and oral leucovorin at a dose of 25 mg twice daily on days 1-7, every 2 weeks. A standard "3 + 3" phase I dose escalation design was utilized.. Fifteen patients were enrolled across three dose levels. Three patients developed DLTs: two patients in level 1 (grade 3 anorexia in 1 and grade 3 anorexia, stomatitis and diarrhea in 1) and one patient in level 2 (grade 3 deep vein thrombosis). No DLT was observed in level 3. Response rate and the disease control rate were 33 and 93 %, respectively. The median PFS and OS were 5.4 and 16.6 months. Ten of 12 patients (83 %) with elevated CA19-9 at baseline had a ≥ 50 % decline.. RD of gemcitabine in GSL was determined as 1,000 mg/m(2). GSL was well tolerable and showed promising results in advanced pancreatic cancer.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Diarrhea; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Leucovorin; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Stomatitis; Survival Analysis; Tegafur; Treatment Outcome; Venous Thrombosis

The combination of bevacizumab and bolus 5-fluorouracil, leucovorin and irinotecan is highly effective in patients with metastatic colorectal cancer (mCRC). This randomised, multicenter, non-comparative phase II trial assessed the efficacy and safety of bevacizumab plus oral capecitabine plus irinotecan (XELIRI) or infusional 5-fluorouracil, leucovorin plus irinotecan (FOLFIRI) as first-line therapy for patients with mCRC.. Patients received bevacizumab 7.5mg/kg on day 1 plus XELIRI (irinotecan 200mg/m(2) on day 1 and oral capecitabine 1,000 mg/m(2) bid on days 1-14) every 3 weeks or bevacizumab 5mg/kg on day 1 plus FOLFIRI (5-fluorouracil 400mg/m(2) on day 1 plus 2,400 mg/m(2) as a 46-h infusion, leucovorin 400mg/m(2) on day 1, and irinotecan 180 mg/m(2) on day 1) every 2 weeks. Patients aged ≥ 65 years received a lower dose of capecitabine (800 mg/m(2) twice daily). The primary endpoint was 6-month progression-free survival (PFS) rate.. A total of 145 patients were enrolled (bevacizumab-XELIRI, n=72; bevacizumab-FOLFIRI, n=73). The 6-month PFS rate was 82% (95% confidence intervals (CI) 71-90%) in the bevacizumab-XELIRI arm and 85% (95% CI 75-92%) in the bevacizumab-FOLFIRI arm. In both the bevacizumab-XELIRI and bevacizumab-FOLFIRI arms, median PFS and overall survival (OS) were 9 and 23 months, respectively. The most frequent toxicities were grade 3/4 neutropenia (bevacizumab-XELIRI 18%; bevacizumab-FOLFIRI 26%) and grade 3 diarrhoea (12% and 5%, respectively).. This randomised non-comparative study demonstrates that bevacizumab-XELIRI and bevacizumab-FOLFIRI are effective regimens for the first-line treatment of patients with mCRC with manageable toxicity profiles.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Fatigue; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Neoplasm Metastasis; Neutropenia; Quality of Life; Time Factors; Treatment Outcome; Venous Thrombosis

This study was designed to assess the toxicity of pelvic radiation therapy, 5-fluorouracil (5-FU) administered by protracted venous infusion, and leucovorin.. Pelvic radiation therapy consisted of 50.4-54 gray (Gy) administered in 28-30 fractions. Systemic treatment consisted of leucovorin (10 mg daily) administered orally and protracted venous infusion of 5-FU. The initial daily 5-FU dose was 150 mg/m(2). Dose escalations were planned in increments of 25 mg/m(2).. Forty eligible patients were registered, of whom 37 were evaluable for chemoradiotherapy-related toxicity. Grade 3 or 4 toxicity secondary to radiation therapy, protracted venous infusion of 5-FU, and leucovorin occurred in 2 of 17 patients at a daily 5-FU dose of 150 mg/m(2), in 5 of 10 patients at a daily 5-FU dose of 175 mg/m(2), and in 5 of 10 patients at a daily 5-FU dose of 200 mg/m(2). Diarrhea was dose-limiting in 7 of 8 patients with Grade 4 toxicity. Venous thrombosis, a treatment-related complication not directly related to chemotherapy or radiation therapy, occurred in 5 of the 40 patients entered into this study. Four thromboses occurred at the site of a central catheter. No thrombotic complications occurred in the last 7 patients, who were given warfarin orally (1 mg daily) during treatment.. Toxicity due to radiation therapy, protracted venous infusion of 5-FU, and leucovorin when 5-FU is given daily at a dose of 150 mg/m(2) is similar to that observed in current chemoradiotherapy regimens for patients with rectal carcinoma. This regimen will be considered as a possible investigational treatment arm of a future trial of adjuvant therapy for rectal carcinoma patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose-Response Relationship, Drug; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Pelvis; Rectal Neoplasms; Venous Thrombosis

Diarrhea is dose-limiting with weekly 5-fluorouracil (5-FU) plus high-dose leucovorin (LV). Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been associated with a decrease in chemotherapy-associated mucosal toxicity. This study was conducted to determine the maximum tolerated dose (MTD) of weekly 5-FU when administered with GM-CSF and high-dose LV. Patients were treated with intravenous LV 500 mg/m2 plus 5-FU weekly for six doses followed by a 2-week rest. GM-CSF 250 mg/m2 was administered subcutaneously 5 days each week. Cohorts were treated with 5-FU at 600, 700, and 800 mg/m2 weekly. Twenty-nine patients were treated. The MTD of 5-FU in this schedule was 700 mg/m2/week, with diarrhea dose-limiting. 5-FU delivered dose intensity at the MTD was 424 +/- 23.7 mg/m2/week, including rest periods. 5-FU and LV pharmacokinetics were not altered by concurrent treatment with GM-CSF. In a weekly schedule with high-dose LV and GM-CSF, the MTD of 5-FU and 5-FU delivered dose intensity were higher than previously reported with 5-FU and LV administered without GM-CSF.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Bone Marrow Diseases; Cohort Studies; Diarrhea; Drug Administration Schedule; Female; Fluorouracil; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infusions, Intravenous; Injections, Intravenous; Injections, Subcutaneous; Intestinal Mucosa; Leucovorin; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms; Peripheral Nervous System Diseases; Severity of Illness Index; Stomatitis; Treatment Outcome; Venous Thrombosis

Portal vein tumor thrombus (PVTT) is common in hepatocellular carcinoma (HCC). Recent studies indicate that more aggressive treatments, including surgical resection or locoregional treatment, may benefit selected HCC patients with PVTT. External radiation therapy and infusion chemotherapy were found to achieve good outcomes; however, the use of low-energy x-ray radiation system (INTRABEAM), intraoperative radiation therapy, and portal vein infusion chemotherapy for PVTT has not been reported. We present a case of HCC with PVTT. The patient underwent hemihepatectomy and thrombectomy along with intraoperative radiotherapy (IORT) using a portable INTRABEAM radiation system. Subsequently, to treat PVTT, portal vein infusion chemotherapy with FOLFOX (leucovorin [Folinic acid], fluorouracil, and oxaliplatin) regimen was administered. There were no obvious post-operative complications. After 20 months follow-up period, no obvious tumor recurrence had been observed, and PVTT gradually disappeared completely.. IORT using the INTRABEAM radiation system combined with portal vein infusion chemotherapy is promising for select patients with PVTT.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Combined Modality Therapy; Fluorouracil; Hepatectomy; Humans; Intraoperative Care; Leucovorin; Liver Neoplasms; Male; Organoplatinum Compounds; Portal Vein; Radiotherapy, Adjuvant; Retrospective Studies; Thrombectomy; Venous Thrombosis

A 65-year-old woman was diagnosed with simultaneous hepatic metastasis of rectal cancer with portal venous tumor thrombi(Vp3)that developed in the bifurcation of the portal vein. Four days from the first visit, abdominal dynamic contrastenhanced CT image on the portal venous phase shows that the tumor thrombi progressed in the main trunk of the portal vein (Vp4). We decided that it was a condition of oncologic emergency and initiated FOLFOXIRI plus BV therapy. After 12 courses, tumor shrinkage and regression of the portal venous tumor thrombi were achieved, but conversion surgery was impossible because the collateral circulation of the hepatic portal region remained. The treatment target was changed to the extension of the survival period. The initiation and reinitiation of FOLFOXIRI plus BV therapy and maintenance of 5-FU/l-LV plus BV therapy contributed to disease control in 24 months and survival period of 36months.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Female; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Organoplatinum Compounds; Portal Vein; Rectal Neoplasms; Venous Thrombosis

Topics: Adenocarcinoma, Mucinous; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colectomy; Colonic Neoplasms; Fluorouracil; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Mesenteric Veins; Mesentery; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Organoplatinum Compounds; Positron Emission Tomography Computed Tomography; Thrombectomy; Treatment Outcome; Venous Thrombosis

A 48-year-old man was administered bevacizumab+FOLFOX for lymph node recurrence of colon cancer in the abdominal cavity, and developed serious thrombosis of the portal system after 6 courses of the chemotherapy. We discontinued it promptly and anticoagulant therapy with urokinase was started immediately, but a complete dissolution was not achieved. Preservation therapy using anticoagulants for a long duration was effective for controling the of clinical symptom of thrombosis. The result of 6 courses of chemotherapy was CR, and the effect continues today, without further treatment 2 years later.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colonic Neoplasms; Fibrinolytic Agents; Fluorouracil; Humans; Leucovorin; Male; Mesenteric Veins; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Recurrence; Urokinase-Type Plasminogen Activator; Venous Thrombosis

The prognosis for hepatocellular carcinoma (HCC) along with portal vein tumor thrombi (PVTT) is poor, and surgery has not been considered an option.. To compare the outcomes and the quality of life (QoL) of patients with HCC and PVTT who underwent hepatic resection and thrombectomy for tumor thrombi in the inferior vena cava and hepatic vein with total hepatic vascular exclusion to the patients who received only chemotherapy.. We retrospectively reviewed the medical records of patients who received hepatectomy and thrombectomy (n=65), and those who received only chemotherapy (n=50). The surgical outcomes, survival, and QoL that was determined using the Functional Assessment of Cancer Therapy-Hepatobiliary instrument were analyzed and compared.. Patients who underwent surgery had a median overall survival of 17 months, compared with patients who underwent chemotherapy for 8 months (P<0.0001). Patients who underwent surgery had a median recurrence-free survival of 14 months, as compared with patients who underwent chemotherapy for 7 months (P<0.0001). The probabilities of 1-year recurrence in the surgery and chemotherapy groups were 27.7 and 70%, respectively (P<0.0001). The QoL total score of the surgery group was significantly higher than that of the control group (P<0.0001). Surgery was slightly, though significantly more cost-effective than chemotherapy based on the quality-adjusted life years.. Hepatectomy and thrombectomy using the total hepatic vascular exclusion, is a viable surgical management for patients with HCC and PVTT, and is associated with longer overall survival and recurrence-free survival and better QoL than chemotherapy alone.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cost-Benefit Analysis; Female; Fluorouracil; Hepatectomy; Hepatic Veins; Hospital Costs; Humans; Kaplan-Meier Estimate; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplastic Cells, Circulating; Organoplatinum Compounds; Quality of Life; Retrospective Studies; Thrombectomy; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis

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

Thrombosis of the inferior vena cava is a life-threatening complication in cancer patients leading to pulmonary embolism. These patients can also be affected by superior vena cava syndrome causing dyspnea followed by trunk or extremity swelling. We report the case of a 61-year-old female suffering from an extended colorectal tumor who became affected by both of the mentioned complications. Due to thrombus formation within the right vena jugularis interna, thrombosis of the inferior vena cava, and superior vena cava syndrome, a combined interventional procedure via a left jugular access with stenting of the superior vena cava and filter placement into the inferior vena cava was performed As a consequence, relief of the patient's symptoms, prevention of pulmonary embolism, and paving of the way for further venous chemotherapy were achieved.

Topics: Antineoplastic Combined Chemotherapy Protocols; Catheterization, Peripheral; Colorectal Neoplasms; Contrast Media; Female; Fluorouracil; Humans; Jugular Veins; Leucovorin; Middle Aged; Organoplatinum Compounds; Palliative Care; Radiography, Interventional; Stents; Superior Vena Cava Syndrome; Tomography, X-Ray Computed; Ultrasonography, Interventional; Vena Cava Filters; Vena Cava, Inferior; Venous Thrombosis

In order to discuss the role of preoperative chemotherapy for colorectal liver metastases, which is used frequently before hepatic resection, even in patients with resectable disease at presentation, we herein report the development of two complications, partial portal vein thrombosis and hepatic steatosis with lobular inflammation, during the course of preoperative chemotherapy with FOLFIRI plus bevacizumab for colorectal liver metastases, which recognition led to timely discontinuation of chemotherapy as well as a change in the surgical strategy to resect the tumors and the damaged liver through advanced techniques. We conclude that duration of treatment and drug doses and combinations may impact the development of chemotherapy-induced liver injury. Surgeons and medical oncologists must work together to devise safe, rational, and oncologically appropriate treatments for patients with multiple colorectal liver metastases, and to improve the understanding of the pathogenesis of chemotherapy-induced liver injury.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Dose-Response Relationship, Drug; Fatty Liver; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Portal Vein; Venous Thrombosis

A 64-year-old man was diagnosed with unresectable cancer of the trachea. He was treated definitively with a novel chemoradiation regimen. Cisplatin-based chemotherapy (ChT) was given for two cycles as induction, followed by concurrent administration of this ChT with external beam radiotherapy (RT) (total dose 60 Gy). An unexpected partial tumour response was noted after the induction of ChT alone. Six weeks after finishing ChT/RT, complete response of the lesion was noted on computed tomography imaging. Two years later, the patient was free of disease. Primary chemoradiation appears to be effective in managing locally advanced tracheal cancer.

Topics: Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Diarrhea; Drug Administration Schedule; Epirubicin; Esophagitis; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Peripheral Nervous System Diseases; Radiography, Thoracic; Radiotherapy Dosage; Tracheal Neoplasms; Treatment Outcome; Venous Thrombosis