levoleucovorin and Disseminated-Intravascular-Coagulation

We describe the case of a 65-year-old woman, known with ulcerative colitis, who presented with progressive headaches, haematomas and rectal bleeding which turned out to be the initial manifestation of disseminated intravascular coagulation (DIC) associated with colorectal cancer. The presentation posed as a general medicine case but turned out to be a rare oncological complication. The patient revealed possible carcinocythaemia and bone marrow infiltration with signet ring-like cells, as indicators of advanced adenocarcinoma. Treatment of the underlying disease resolved the DIC and contributed to prolonged survival. Subsequently, we reviewed the English literature since 1990 on similar cases and demonstrated that this association is extremely rare and is associated with a poor prognosis. Prompt recognition and treatment of the underlying disease is confirmed to be of utmost importance to prolong (progression-free) survival.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Deoxycytidine; Disseminated Intravascular Coagulation; Fatal Outcome; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Oxaloacetates; Paraneoplastic Syndromes; Sigmoid Neoplasms

Acute disseminated intravascular coagulation (DIC) is a rare but severe complication of gastric adenocarcinoma. Conventional treatments, such as fresh frozen plasma, platelet replacement and heparin injections, are disappointing. The only way to correct this fatal condition is to control the underlying cancer promptly by effective chemotherapy. Here the successful initial control of acute DIC in gastric cancer patients with weekly EEPFL chemotherapy is reported.. Advanced gastric cancer patients complicated with acute DIC were eligible. Patients were treated with weekly EEPFL therapy (etoposide 40, epirubicin 10, cisplatin 25, 5-fluorouracil 2200 and leucovorin 120 mg/m2 ). Response, survival and toxicity were evaluated.. From April 1997 to April 1999, six patients were included in this study. All patients received EEPFL chemotherapy. Clinical and laboratory evidence of acute DIC stabilized quickly after starting chemotherapy. Four patients showed a partial response, one stable disease and one progressive disease. The toxicity was mild and well tolerated. Median survival was 28 weeks (12, 14, 26, 30, 30 and 32 weeks). All patients suffered from a relapse of DIC after initial successful control and died within 30 days of clinical and laboratory evidence of acute DIC relapse.. EEPFL therapy is an effective chemotherapy regimen for patients with advanced gastric cancer associated with acute DIC. The prognosis is poor if the DIC relapses after the initial successful control.

Topics: Acute Disease; Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disseminated Intravascular Coagulation; Epirubicin; Etoposide; Female; Fluorouracil; Humans; Leucovorin; Male; Stomach Neoplasms; Survival Rate

Oxaliplatin is one of the most commonly used drugs for patients with colorectal cancer. It has rarely been associated with disseminated intravascular coagulation (DIC) with only 3 previously reported cases. In all those instances, the patients had started receiving oxaliplatin, developed evidence of DIC during the course of planned treatment, and recovered with supportive care. We report a case of a 71-year-old man with colorectal cancer treated successfully with an oxaliplatin-based regimen who had disease relapse after 3 years. When treated again with oxaliplatin, he developed signs of an acute hypersensitivity reaction, and eventually had signs and symptoms consistent with DIC despite appropriate management. This case is unique in that a DIC reaction evolving from a hypersensitivity reaction occurred after the patient had already tolerated the drug years earlier. It suggests a possible immune-mediated etiology to this rare occurrence that should be kept in mind while utilizing this commonly employed drug.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Creatinine; Disseminated Intravascular Coagulation; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Male; Organoplatinum Compounds; Oxaliplatin; Recurrence

A 32-year-old woman was found to have a gastric adenocarcinoma with multiple bone metastases. Chemotherapy in the first, second and third-line was not effective. Blood examinations showed disseminated intravascular coagulation(DIC)at the end of the second-line chemotherapy. The fourth-line chemotherapy, infusional 5-fluorouracil and levofolinate calcium was performed. This resulted in a good response for DIC. This palliative therapy was effective and safety.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Disseminated Intravascular Coagulation; Female; Fluorouracil; Gastrectomy; Humans; Levoleucovorin; Stomach Neoplasms; Treatment Outcome

Disseminated intravascular coagulation (DIC) is a rare complication of advanced gastric cancer (AGC). Despite reports of the efficacy of chemotherapy for AGC with DIC, little is known of platinum-based doublet therapy.. We conducted a single-institute, retrospective chart review of 500 consecutive chemotherapy-naïve patients with advanced gastric adenocarcinoma (recurrent or metastatic) from November 2010 to November 2015.. Six patients were diagnosed with AGC with DIC (1.2%); five (1.0%; 3 men, 2 women) received platinum-based doublet chemotherapy. All patients exhibited improved DIC and thrombocytopenia and survived for >100 days (range=114-313) with no therapy-related mortality. Grade ≥3 adverse effects included neutropenia, anemia, hyponatremia, catheter-related infection and diarrhea (maximum: 2 patients each).. Fluoropyrimidine plus platinum combination therapy was effective against DIC and yielded acceptable survival outcomes. Combination chemotherapy should be considered as a primary therapy for AGC with DIC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disseminated Intravascular Coagulation; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Disseminated Intravascular Coagulation; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin

Disseminated carcinomatosis of the bone marrow is often accompanied by disseminated intravascular coagulation syndrome (DIC). This condition is rarely caused by colorectal cancer, and there are no established therapies.. A 66-year-old woman was admitted to our hospital because of DIC. She had been diagnosed with cecal cancer and multiple metastases of the lymph nodes, liver, and bone. She was diagnosed with disseminated carcinomatosis of the bone marrow and treated with systemic chemotherapy by modified FOLFOX6 (mFOLFOX6). Subsequently, the DIC rapidly resolved, and she was discharged from the hospital.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Bone Marrow Neoplasms; Disseminated Intravascular Coagulation; Fatal Outcome; Female; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds

Topics: Adenocarcinoma; Aged; Anemia; Antifibrinolytic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Coagulation; Carcinoma, Squamous Cell; Cecal Neoplasms; Disseminated Intravascular Coagulation; Fatal Outcome; Female; Fibrinogen; Fibrinolysis; Fluorouracil; Heart Diseases; Hemorrhage; Humans; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Multiple Organ Failure; Neoplasms, Multiple Primary; Organoplatinum Compounds; Postoperative Complications; Thrombosis; Tranexamic Acid; Vulvar Neoplasms

We report the case of a 62-year-old woman with a metastatic gastric cancer complicated by diffuse bone marrow carcinomatosis, disseminated intravascular coagulation (DIC) and microangiopathic hemolytic anemia (MHA) treated by modified FOLFOX-6 as front-line chemotherapy regimen. This chemotherapy showed clinical, morphological and biological efficiency and safety in this rare and severe hematological complication at initial diagnosis. Furthermore, this is the first case of diffuse bone carcinomatosis from a gastric cancer to be monitored by positron emission tomography integrated computed tomography (PET-CT) scan using 18-fluorodeoxyglucose (18-FDG).

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Carcinoma; Carcinoma, Signet Ring Cell; Diagnostic Imaging; Disease Progression; Disseminated Intravascular Coagulation; Drug-Related Side Effects and Adverse Reactions; Fatal Outcome; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Purpura, Thrombotic Thrombocytopenic; Sensitivity and Specificity; Stomach Neoplasms; Treatment Outcome

We report on a 65-year-old female patient with a recent diagnosis of adenocarcinoma of the sigmoid colon and massive hematochezia in the context of a general bleeding disorder.. Disseminated malignant disease with hepatic metastases as well as bone marrow involvement was demonstrated. Moreover, circulating tumor cells were demonstrated by flow cytometry. The patient had right lower quadrant abdominal pain due to a spontaneous psoas intramuscular hematoma.. At the time of admission to our hospital, the patient displayed microangiopathic hemolytic anemia and secondary hyperfibrinolysis with a pronounced bleeding tendency. Moreover, there was an acute renal failure which improved with fluid resuscitation. With immediate chemotherapy consisting of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX regimen) and cetuximab initiated with the second course, plasmatic coagulation could be stabilized. Consequently, treatment with tranexamic acid, fibrinogen, fresh frozen plasma as well as red blood cell and platelet infusions could be stopped. Continuation of chemotherapy was possible on an outpatient basis and the further course was associated with a good quality of life until her near end. The patient died at home 7 months after initial diagnosis of her colon cancer due to progressive disease with CNS metastases.. Disseminated intravascular coagulation with microangiopathic hemolysis and secondary hyperfibrinolysis is a rare albeit possible event in disseminated colorectal cancer, especially when the bone marrow is involved. Treatment of the underlying cause is the most important therapeutic measure.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Neoplasms; Brain Neoplasms; Cetuximab; Disease Progression; Disseminated Intravascular Coagulation; Fatal Outcome; Female; Fluorouracil; Gastrointestinal Hemorrhage; Hematoma; Hemorrhagic Disorders; Humans; Leucovorin; Liver Neoplasms; Neoplastic Cells, Circulating; Organoplatinum Compounds; Palliative Care; Purpura, Thrombotic Thrombocytopenic; Retroperitoneal Space; Sigmoid Neoplasms; Tomography, X-Ray Computed

Disseminated intravascular coagulation (DIC) is a complication that may be experienced by patients with solid tumors. The prognosis of solid tumors with DIC is much poorer than those without DIC. Although treatment of the underlying disease is critical for improvement of DIC, the efficacy and safety of chemotherapy in patients with DIC associated with colorectal cancer are not clear. A 50-year-old man with advanced rectal cancer and multiple liver metastases experienced DIC during third-line treatment with cetuximab plus irinotecan, following 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) plus bevacizumab and 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab. Combination chemotherapy consisting of FOLFOX plus bevacizumab was reintroduced. Although platelet and fresh-frozen plasma transfusions were required daily before chemotherapy, the patient's laboratory values improved after two cycles of chemotherapy, without severe toxicity. The patient was discharged, and FOLFOX plus bevacizumab has been continued on an outpatient basis without sign of recurrence of DIC as of December 2010 (4 months after initiation of chemotherapy). This case suggests that reintroduction of combination chemotherapy with FOLFOX plus bevacizumab is effective and feasible in patients with colorectal cancer with DIC and that chemotherapy may be a treatment option for such patients.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Disseminated Intravascular Coagulation; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Rectal Neoplasms

A 71-year-old man with eosinophilia was given a diagnosis of poorly differentiated adenocarcinoma of the rectum. Further examination showed that it had invaded the bone marrow. He had disseminated intravascular coagulation (DIC) from disseminated carcinomatosis of the bone marrow after colostomy. Chemotherapy (mFOLFOX6) was successful and his eosinophil count, DIC score and tumor markers normalized. We were able to continue chemotherapy after 5 months from the outbreak of disseminated carcinomatosis of the bone marrow. It is said that disseminated carcinomatosis of the bone marrow has a poor prognosis, but we were able to obtain a good response in this case by chemotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Carcinoma; Disseminated Intravascular Coagulation; Eosinophilia; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Rectal Neoplasms

A 45-year-old man was admitted to our hospital because of disseminated intravascular coagulation syndrome (DIC) and severe pain in his back and lumbar. Abdominal CT scan demonstrated lymph node enlargement in the whole body. FDG-PET revealed abnormal uptake of FDG in the thickening wall of the descending colon and the entire skeleton. Colonoscopy was performed continuously and revealed a poorly-differentiated adenocarcinoma of the descending colon. He was treated with the systemic chemotherapy of modified FOLFOX6 (mFOLFOX6). After one course of the treatment, DIC was resolved and severe back pain and lumbargo were improved.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Colonic Neoplasms; Disseminated Intravascular Coagulation; Fatal Outcome; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds

Cancer-related acute disseminated intravascular coagulation (DIC) is uncommon, but it is a severe complication resulting in a very dismal prognosis. Choosing the appropriate chemotherapy agents to treat the underlying cancer and stop the acute DIC process effectively, while avoiding chemotherapy-induced myelosuppression which may contribute to bleeding-related mortality, is difficult. Acute DIC in breast cancer is a rare condition and is not well studied. Therefore, we designed this study to determine the clinical characteristics and effective treatment for breast cancer patients with acute DIC.. From March 1996 to November 2008, patients with histologically proven breast cancer who presented with acute DIC at National Taiwan University Hospital were retrospectively analyzed.. Sixteen patients were included in the study. Thirteen patients with breast cancer-related acute DIC were treated with various kinds of chemotherapy, one with tamoxifen, and two with supportive care only. Four patients responded to treatment; three of the responders received vinorelbine with high-dose 5-fluorouracil and leucovorin (HDFL), the other received vinorelbine with cisplatin. The median survival of the responders and non-responders was 13 months and 0.5 month (p<0.001). There were no grade 3 or 4 hematologic or non-hematologic toxicities in the patients receiving vinorelbine-HDFL.. Vinorelbine plus HDFL is considered a safe and effective palliative treatment of choice for breast cancer patients with acute DIC. Further prospective study is warranted.

Topics: Acute Disease; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disseminated Intravascular Coagulation; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Middle Aged; Retrospective Studies; Vinblastine; Vinorelbine

A 66-year-old man was referred to our hospital because of a two-week history off ever and low back pain. There was a hard anal mass on rectal examination. Colonoscopy and computed tomography showed anal adenocarcinoma, multiple metastases to lymph nodes and bones. Blood test showed severe disseminated intravascular coagulation (DIC). Microscopic examination of the bone marrow aspirate revealed disseminated carcinomatosis of the bone marrow. Systemic chemotherapy (mFOLFOX6) was started, then remission of DIC and shrinkage of the tumor were observed. Although the patient had cerebral infarction during the first course of chemotherapy, he received nine courses of treatment. He died six months later because of cerebellar hemorrhage.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Bone Marrow Neoplasms; Carcinoma; Disseminated Intravascular Coagulation; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds

A 73-year-old woman with liver metastasis underwent implantation of an infusion catheter-port system for hepatic arterial infusion chemotherapy. She developed multiple infarctions caused by disseminated intravascular coagulation (DIC) due to liver metastases. The hypercoagulability syndrome associated with cancer (known as Trousseau's syndrome) is considered a cause of cerebral infarction. Among the complications of the implantation of an infusion catheter-port system, Trousseau's syndrome may be one of the causes.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cerebral Infarction; Colorectal Neoplasms; Disseminated Intravascular Coagulation; Female; Fluorouracil; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms

A 49-year-old man was hospitalized because of a 2-month history of purpura in his extremities and for back pain. Laboratory findings showed alkaline phosphatase to be greatly elevated, and platelet counts and coagulation factor showed that the patient had disseminated intravascular coagulation (DIC). Compression fractures of the thoracic vertebrae were found on radiological examination. The histological findings from bone marrow showed metastasis of adenocarcinoma with signet-ring cells, although the primary site was unknown. To reduce tumor cells in number and improve DIC, 11 cycles of 5-Fluorouracil and leucovorin therapy were done, and the patient survived for 12 months. Autopsy showed a 0.8 cm diameter, poorly differentiated adenocarcinoma with the signet-ring cell type in the lamina propria of the Vater's ampulla. Many metastatic foci and micro tumor emboli were found in the lung and in bone marrow. The sections of the stomach, the gallbladder, urinary bladder, prostate, and thyroid gland showed no malignant cells. These findings suggest that the origin of the cancer may have been located in the Vater's ampulla. This is a rare case of an ampullary tumor of poorly differentiated adenocarcinoma with the signet-ring cell type, without jaundice but with multiple metastasis. 5-Fluorouracil and leucovorin were effective for increasing survival time and improving quality of life.

Topics: Ampulla of Vater; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Carcinoma, Signet Ring Cell; Common Bile Duct Neoplasms; Disseminated Intravascular Coagulation; Fatal Outcome; Fluorouracil; Humans; Jaundice; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplastic Cells, Circulating; Quality of Life

Microangiopathic hemolytic anemia (MAHA) and disseminated intravasal coagulation (DIC) as initial paraneoplastic symptoms of a solid tumor present a rare clinical situation.. In 1998 a female patient was admitted due to multiple thrombosis, thrombocytopenia and fever. The initial diagnostic procedures revealed peri-aortic lymphomas and a tumor bulk (7 x 8 cm) in the upper abdomen. Gastroscopy revealed a 2 cm ulcer at the back side of the gastric corpus. Histologically, a signet-ring cell carcinoma was diagnosed. Final diagnosis stated a multilocular metastasising gastric cancer with infiltration of bone, peritoneum and dura and signet-cell infiltration of the bone marrow. Hematologic investigation in view of multiple paraneoplastic thrombosis revealed a microangiopathic hemolytic anemia associated with disseminated intravasal coagulation. Parallel to initial symptomatic therapy of coagulopathy, systemic cytostatic therapy with CDDP and VP-16 was initiated. In addition, radiotherapy of the brain was performed. After histologic confirmation of the diagnosis, weekly therapy with 5-FU (2600 mg/m2) and folinic acid (500 mg/m2) according to the Ardalan protocol was performed. After first signs of moderate response, oxaliplatin (60 mg/m2, day 1) was added. Although the chemotherapy dose had to be reduced due to prolonged neutropenia, the disturbances of hemostasis resolved completely resulting in reduced substitution rates with fresh frozen plasma (FFP) and platelets. Unfortunately, the patient died at home due to pulmonary embolism.. Tumor-associated hemostaseologic alteration requires immediate substitution of FFP and platelets. However, it should be followed by specific therapy of malignancy, since tumor-induced metabolites (e.g. mucin) maintain the alteration of hemostasis. Chemotherapy may therefore be the best strategy to prevent complications such as MAHA and DIC.

Topics: Algorithms; Anemia, Hemolytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Neoplasms; Carcinoma, Signet Ring Cell; Cisplatin; Diagnosis, Differential; Disseminated Intravascular Coagulation; Etoposide; Female; Fluorouracil; Hemorrhagic Disorders; Humans; Leucovorin; Middle Aged; Neoplasm Metastasis; Precancerous Conditions; Stomach; Stomach Neoplasms; Thrombocytopenia

Acute disseminated intravascular coagulation (DIC) is a severe complication of gastric adenocarcinoma, and most of the patients die within 1-3 weeks. We have treated five such patients with an empirical non-myelosuppressive HDFL regimen (weekly 24h infusion of high-dose 5-fluorouracil 2600 mg/m2 and leucovorin 300 mg/m2). Within 2 weeks of starting the treatment the clinical and laboratory evidence of acute DIC quickly resolved in all five patients. HDFL not only caused no further myelosuppression, but also resulted in normalization of the patient's haemogram within a few weeks. Other anti-cancer drugs could then be safely added. Three patients had a survival time of more than 6 months. We suggest that HDFL is an ideal initial treatment for gastric cancer complicated by acute DIC.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Disease-Free Survival; Disseminated Intravascular Coagulation; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Stomach Neoplasms; Survival Analysis; Thrombocytopenia; Treatment Outcome

Topics: Aspartate Aminotransferases; Blood Coagulation Factors; Child; Disseminated Intravascular Coagulation; Female; Heparin; Humans; Leucovorin; Methotrexate; Osteosarcoma

Topics: Adult; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Humans; Leucovorin; Lymphatic Diseases; Male; Methotrexate