levoleucovorin and Hemorrhage

Colon cancer is extremely rare in children. This article reports three cases of adenocarcinoma of the colon. A 12-year-old boy, a 13-year-old boy, and a 13-year-old girl presented with constipation and abdominal enlargement over a two-month duration. Abdominal ultrasound and barium enema confirmed a stenotic segment at the rectum with obvious shouldering. Adenocarcinoma was diagnosed following colonoscopic biopsy and laparotomy. We conclude that any child presenting with unexplained persistent constipation, abdominal distension or bleeding per rectum, colon cancer should be suspected and investigated with endoscopy or barium enema.

Topics: Abdomen; Adenocarcinoma; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Barium Sulfate; Child; Colonoscopy; Colorectal Neoplasms; Female; Fluorouracil; Hemorrhage; Humans; Leucovorin; Male; Neoplasm Staging; Organoplatinum Compounds; Tomography, X-Ray Computed; Ultrasonography

The anti-angiogenic agent bevacizumab (Avastin) has been rationally designed to target vascular endothelial growth factor (VEGF), a key mediator of tumor angiogenesis. Based on its limited roles in adults, VEGF inhibition using bevacizumab would be expected to have limited side effects. Furthermore, because its mechanism of action is different to that of standard chemotherapeutic agents, bevacizumab would not be expected to cause typical cytotoxic agent-related toxicity or to exacerbate the toxicity of concomitant chemotherapy. We have reviewed clinical trials published to date, primarily in metastatic colorectal cancer, and describe the safety profile of bevacizumab. The review focuses on hypertension, proteinuria, arterial thrombosis, effects on wound healing, bleeding and gastrointestinal (GI) perforation, which are the principal bevacizumab-related events seen in clinical trials. These events are for the most part mild to moderate in severity and clinically manageable (hypertension, proteinuria, minor bleeding) or occur uncommonly (wound healing complications, GI perforations and arterial thrombosis). The side-effect profile of bevacizumab makes it a suitable adjunct to standard chemotherapy in settings where efficacy has been demonstrated, and it is now approved for use in the USA, the European Union and other markets worldwide.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Clinical Trials as Topic; Colorectal Neoplasms; Fluorouracil; Hemorrhage; Humans; Hypertension; Incidence; Intestinal Perforation; Leucovorin; Proteinuria; Thrombosis; Vascular Endothelial Growth Factor A; Wound Healing

Topics: Adult; Antidotes; Drug-Related Side Effects and Adverse Reactions; Early Diagnosis; Hemorrhage; Humans; Immunosuppressive Agents; Leucovorin; Male; Methotrexate; Mucous Membrane; Pancytopenia; Psoriasis; Skin; Treatment Outcome; Withholding Treatment

Initial treatment with either neoadjuvant chemoradiation (CRT) or induction FOLFOX (5-Fluorouracil, leucovorin, and oxaliplatin) chemotherapy followed by CRT is considered standard treatment for locally advanced rectal cancer. We compared patient-reported outcomes (PRO) during CRT in patients who had received induction chemotherapy versus those who did not.. We reviewed records of patients with locally advanced rectal cancer who were treated with CRT between September 2009 and October 2014, and who had completed ≥ 4 PRO assessments during treatment. Clinician- and patient-reported toxicities were collected each week during treatment. We fit binomial generalized linear models to maximum toxicity scores across all patients' visits.. Of 123 patients with ≥ 4 PRO assessments, 87 (71%) patients reported a clinically meaningful PRO score of 3 or higher for diarrhea, and 91 (74%) patients reported a PRO score of ≥ 3 for urgency, during 1 or more weeks of treatment, corresponding to 'very frequent' or worse. Of 116 patients who had also completed ≥ 4 clinician-reported assessments for descriptive analysis, clinically significant diarrhea (Common Terminology Criteria for Adverse Events grade ≥ 2) was reported in 9% of patients, and grade 2 proctitis and cystitis were reported in 20% and 4%, respectively. Eighty-four (68%) patients had undergone induction chemotherapy prior to CRT. Patients who received induction chemotherapy had 68% lower odds of experiencing significant urgency (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.11-0.95; P = .04), 76% lower odds of bleeding (OR, 0.24; 95% CI, 0.1-0.62; P < .01), and 75% lower odds of tenesmus (OR, 0.25; 95% CI, 0.11-0.6; P < .01) versus those treated with upfront CRT.. Based on PROs, a high proportion of patients experienced clinically significant symptoms during pelvic CRT, with diarrhea and urgency being most commonly reported. This appears to be under-reported on clinician-reported assessments. Delivery of induction chemotherapy was associated with lower odds of experiencing urgency, bleeding, and tenesmus on PROs during subsequent CRT, with no significant impact on diarrhea and rectal pain.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Diarrhea; Female; Fluorouracil; Hemorrhage; Humans; Induction Chemotherapy; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Patient Reported Outcome Measures; Proctectomy; Radiotherapy, Intensity-Modulated; Rectal Neoplasms; Rectum; Retrospective Studies; Urination Disorders; Young Adult

Bevacizumab (Avastin(®)) was approved in Japan in April 2007 for patients with advanced or metastatic colorectal cancer. To address the limited clinical experience in Japanese patients, a post-approval surveillance study was undertaken in bevacizumab-treated patients in Japan.. Bevacizumab (5 or 10 mg/kg every 2 weeks) was administered with chemotherapy; patients were observed for 26 weeks from initiation of treatment. The primary objective was to investigate the incidence of adverse drug reactions, particularly those of interest for bevacizumab. Univariate and multivariate analyses were performed to identify potential risk factors for adverse drug reactions.. In total, 2712 patients were registered and 2696 patients were included in the safety analysis. Hypertension (13.1%), hemorrhage (10.5%) and proteinuria (4.5%) were the most common adverse drug reaction. The incidences of serious adverse drug reactions were low: gastrointestinal perforation occurred in 0.9% of patients, hemorrhage in 1.3%, arterial thromboembolic events in 0.3%, venous thromboembolic events in 1.3% and wound-healing complications in 0.4%. The incidence of bevacizumab-specific adverse drug reactions was not influenced by the bevacizumab dose. Multivariate analyses identified risk factors for the following adverse drug reactions: hypertension (prior/concurrent hypertension); tumor-associated bleeding (performance status, prior/concomitant anticoagulant or nonsteroidal anti-inflammatory drug use); proteinuria (sex, performance status, prior/concurrent diabetes and proteinuria); gastrointestinal perforation (primary tumor in situ, concurrent nonsteroidal anti-inflammatory drug use); venous thromboembolic event (treatment stage, port insertion).. The safety profile of bevacizumab-containing regimens in this Japanese population was comparable with studies performed in Western countries. Bevacizumab is generally well tolerated in Japanese patients with advanced or metastatic colorectal cancer.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Fluorouracil; Heart Failure; Hemorrhage; Humans; Hypertension; Japan; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Product Surveillance, Postmarketing; Proteinuria; Risk Factors

The authors report a case with spontaneous renal hemorrhage caused by invasive mole. The diagnosis was gestational trophoblastic disease (GTD), with metastasis to brain, kidneys, and lungs at Stage IV. The patient was given etoposide-methotrexate-actinomycin D plus cyclophosphamide-vincristine (EMACO) treatment regimen for 11 times including three times with consolidation chemotherapies. Laparoscopically-assisted vaginal hysterectomy (LAVH) + laparoscopic-assisted left renal excision + evacuation of the left perirenal hematoma were performed during the eighth chemotherapy.. Post-operational pathological examination revealed trophoblasts within the lesions present in uterine fundus and the residue images of a few trophoblasts present in the left renal mass.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Dactinomycin; Doxorubicin; Etoposide; Female; Hemorrhage; Humans; Hydatidiform Mole, Invasive; Kidney Diseases; Leucovorin; Methotrexate; Pregnancy; Uterine Neoplasms; Vincristine

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

To assess the efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents in the treatment of metastatic colorectal cancer (mCRC).. Seventy-seven mCRC patients received BEV plus 5-Fu type, oxaliplatin or irinotecan-based chemotherapy. The clinical efficacy and bevacizumab-related adverse reactions were observed. The efficacy assessment was conducted after at least 2 cycles of BEV therapy. The adverse reactions were recorded in each therapy cycle. Among the 77 cases, 64 patients had finished the efficacy assessment. The adverse reactions in all patients were assessed.. The overall response rate (ORR) of BEV plus chemotherapy regimen was 18.75% (12/64), and the disease control rate (DCR) was 75.0% (48/64). In 27 patients who received the regimen as first-line treatment, the ORR reached 37.0% (10/27), while the DCR was 85.2%. Four patients with potentially resectable lesions became resectable after the regimen and received R0 resection of the liver metastases successfully. Twenty-five patients who received the regimen as second line therapy had poor result with ORR 8.0% and DCR 76.0%. Hypertension was observed in 12 cases, with 8 cases of grade 1, 3 cases of grade 2, 1 case of grade 3. Various bleedings occurred in 24/77 cases (31.2%), all were of grade 1-2, including 17 cases of epistaxis, grade 1 hemorrhoid bleeding in one case, hematuria in 3 case (2 of grade 1, 1 of grade 2), GI bleeding in 2 cases, hemoptysis in 1 case (grade 2), and proteinuria in 4 cases (grade 1). Intestinal perforation occurred in 1 case (0.3%). In two patients who had incomplete intestinal obstruction history appeared exacerbated intestinal obstruction symptoms after the application of BEV plus CPT11 regimen.. BEV plus chemotherapy regimen as first-line treatment can improve the ORR and DCR of mCRC patients. When it was used as second- or later-line therapy, it may display satisfied DCR, although with a poor efficacy. The bevacizumab-related toxicity is mild and can be well tolerated.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Colonic Neoplasms; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Hemorrhage; Humans; Hypertension; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Proteinuria; Rectal Neoplasms; Remission Induction; Young Adult

We now describe the first example of a patient who developed perirenal hematoma during the course of bevacizumab-containing chemotherapy. A 59-years-old woman with metastatic rectal cancer treated with bevacizumab, who developed low back pain after 11 cycles of chemotherapy. CT-scan was consistent with perirenal hematoma and discontinuation of bevacizumab resulted in symptomatic improvement. Nontraumatic perirenal hematoma is a rare condition that can cause shock in severe cases. Given that several types of bleeding complication are known to be associated with bevacizumab treatment, we concluded that bevacizumab likely contributed to the perirenal hematoma in this case. Although the appropriate modification of bevacizumab treatment in the setting of perirenal hematoma is still unclear, physicians should be aware of this potential bevacizumab-associated bleeding complication.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Female; Fluorouracil; Hematoma; Hemorrhage; Humans; Leucovorin; Liver Neoplasms; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Time Factors; Tomography, X-Ray Computed

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Endothelial Growth Factors; Fluorouracil; Hemorrhage; Humans; Intercellular Signaling Peptides and Proteins; Leucovorin; Lymphokines; Neoplasm Metastasis; Thrombosis; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Warfarin

We conducted a pilot study in 20 patients with high-risk or recurrent/refractory non-Hodgkin's lymphoma (NHL) using high-dose sequential chemotherapy (HDSC) and autologous hematopoietic cell transplantation (AHCT). After cytoreduction with standard salvage therapy, HDSC/AHCT was administered in 4 phases at 2- to 4-week intervals. Phase 1 consisted of cyclophosphamide 7 g/m2 followed by granulocyte colony-stimulating factor (G-CSF) at 10 microg/kg per day and leukapheresis upon recovery from white blood cell nadir. The hematopoietic cell product was enriched by Percoll gradient separation and purged with a B-cell or T-cell monoclonal antibody panel and complement. Phase 2 consisted of methotrexate 8 g/m2 with leucovorin rescue and vincristine 1.4 mg/m2. Phase 3 was etoposide 2 g/m2 with G-CSF 5 microg/kg per day. In phase 4, the preparative regimen of mitoxantrone 60 mg/m2 and melphalan 180 mg/m2 was administered followed by AHCT. The NHL histologies were diffuse large cell, follicular/diffuse mixed, small noncleaved cell, T-cell-rich B-cell, lymphoblastic, and peripheral T cell. The remission status was first partial remission (PR1; n = 1) or beyond first complete remission (post-CR1; n = 19). Of the 20 patients enrolled, 11 proceeded through all 4 phases. Nine were removed from the study after the first or second phase because of progressive disease (n = 5), poor hematopoietic cell mobilization (n = 1), excessive toxicity (n = 2), and chronic active hepatitis C (n = 1). Treatment-related toxicities in the remaining 11 transplant recipients were cardiomyopathy, hemorrhagic cystitis, persistent cytopenias, acute renal failure, abnormal liver function test results, and infectious complications. There were no treatment-related deaths. Eight of the 11 transplant recipients were alive, 6 without disease, at a median follow-up of 2.7 years. The estimated median 2-year event-free survival was 55%, and overall survival was 70%. We conclude that HDSC/AHCT in refractory/recurrent NHL is associated with considerable acute and chronic toxicities. Given the toxicity profile, efficacy data were not sufficiently promising to warrant further study.

Topics: Acute Kidney Injury; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Bone Marrow Purging; Cardiomyopathies; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Cyclophosphamide; Cystitis; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Etoposide; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Infections; Leucovorin; Life Tables; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Middle Aged; Mitoxantrone; Pilot Projects; Salvage Therapy; Survival Analysis; Survival Rate; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Vincristine

The authors evaluated a high-intensity inpatient regimen using augmented but subtransplantation doses of multiple agents in patients with metastatic breast cancer. Two high-dose courses were given in an attempt to improve the efficacy of high-dose regimens using a single course.. Forty women received treatment between October 1988 and October 1991. The median age was 38 years (range, 24-56 years). Twenty-five patients were receiving their first chemotherapy for metastatic disease; 15 patients had received one or more prior regimens. The patients received two courses of chemotherapy, which consisted of the following: cyclophosphamide 1500 mg/m2 intravenously (i.v.) on days 1 and 2; doxorubicin 45 mg/m2 i.v. on days 1 and 2; cisplatin 20 mg/m2 i.v. on days 1, 2, 3, 8, 9, and 10; 5-fluorouracil 1000 mg/m2 on days 8, 9, and 10 (continuous infusion); methotrexate 100 mg/m2 i.v. on days 15 and 22; leucovorin 15 mg/m2 i.v. or by mouth for four doses beginning 24 hours after methotrexate. Etoposide 400 mg/m2 i.v. on days 1, 2, and 3 was substituted for doxorubicin in 14 patients who had received prior doxorubicin.. Twenty-nine of 40 patients (73%) had objective response to therapy, with 10 (25%) complete responses. Four patients who obtained a complete response remain disease-free at 14, 21, 28, and 32 months, respectively; all of these patients received this regimen as first-line therapy for metastatic disease. Myelosuppression was severe, with median durations of leukocytes less than 1000/microliters and platelets less than 50,000/microliters of 15 days (range, 7-48 days) and 13 days (range, 3-49 days), respectively. Moderate or severe mucositis occurred in 56 of 68 courses. Four patients (10%) had treatment-related deaths.. This regimen produced high overall response and complete response rates compared with standard regimens. However, only 15% of patients who received this therapy as first-line treatment for metastatic breast cancer remain disease-free, and median response duration was shorter than that reported using high-dose therapy with bone marrow support. Toxicity with this regimen was greater than anticipated, although myelosuppression and stomatitis would be reduced by the use of cytokines. This regimen does not improve results achieved with standard therapy sufficiently to justify its toxicity and expense.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Cisplatin; Cyclophosphamide; Doxorubicin; Etoposide; Female; Fluorouracil; Follow-Up Studies; Hemorrhage; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Methotrexate; Middle Aged; Neutropenia; Remission Induction; Survival Rate; Thrombocytopenia

Short treatment with four cytostatics in acute granulocytic leukemia induced aplasia and reduction of total leukemic cells in 50 over 59 patients. Complete remission occured in 30 and 20 died with infectious complications during induction. Short induction treatment allowed a reduction of induction period and so a reduction of high risk period of induction before completion of complete remission.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Cytarabine; Daunorubicin; Drug Administration Schedule; Female; Fever; Hemorrhage; Humans; Leucovorin; Leukemia, Myeloid, Acute; Male; Methotrexate; Middle Aged; Pyruvaldehyde; Remission, Spontaneous; Sepsis

Topics: Floxuridine; Geriatrics; Hemiplegia; Hemorrhage; Infusions, Intra-Arterial; Infusions, Parenteral; Leucovorin; Mechlorethamine; Methotrexate; Mortality; Neoplasms; Thiotepa; Toxicology; United States; United States Department of Veterans Affairs

Topics: Aminopterin; Animals; Bloodletting; Carbon Tetrachloride; Dogs; Folic Acid; Hematologic Tests; Hemorrhage; Leucovorin; Phlebotomy; Radiation Effects; X-Rays