Serum uric acid as a surrogate marker of favorable response to bevacizumab treatment in patients with metastatic colon cancer.

Bevacizumab is a monoclonal antibody which is a vascular endothelial growth factor inhibitor. It obscures vascularization of tumor tissue and damages intratumoral microcirculation. The damaged intratumoral microcirculation leads to tissue hypoxia and results in increase of uric acid level. The main aim of our study was to investigate the relationship between uric acid change and response to bevacizumab therapy. This study included a total of 158 patients with metastatic colorectal cancer who had received bevacizumab therapy. The number of male patients was 100 (63.3 %) while female patients number was 58 (37.7 %). The median age was 61 (29-83). There was relationship between increase of uric acid level of third month uric acid level and stable disease (p < 0.001). There was a significant overall survival increased in the group with increased uric acid level (p < 0.001). The decline of CEA level was related to uric acid level (p < 0.022). In conclusion, this study is the first showing significant increases of serum uric acid in patients with metastatic colorectal cancer who favorably responded to chemotherapy with bevacizumab. But further studies are justified to test whether monitoring uric acid levels might predict clinical outcomes of patients with metastatic colorectal cancer.

Comparison of hematologic toxicity between 3DCRT and IMRT planning in cervical cancer patients after concurrent chemoradiotherapy: a national multi-center study.

PURPOSE: To compare the incidence and severity of acute and chronic hematologic toxicity (HT) in patients treated with three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) for curative treatment of cervical cancer and to ascertain the dosimetric parameters of two techniques associated with acute and chronic HT. MATERIALS AND METHODS: A total of 127 patients with cervical cancer receiving concomitant pelvic radiotherapy (RT) and cisplatin were evaluated. Pelvic bone marrow (BM) was contoured for each patient and divided into five sub-regions: lumbosacrum (LS), ilium (IL), lower pelvis (LP), pelvis (P), and whole pelvis (WP). The volume of each BM region receiving 10, 20, 30, and 40 Gy was calculated (V10, -V20, -V30, and -V40). The lowest level of hemoglobin, leukocyte, neutrophil, and platelet counts were obtained during chemoradiotherapy and six months after RT. The nadir values were graded according to Common Terminology Criteria for Adverse Events (version 3.0). RESULTS: Grade 2 or greater acute anemia, leukopenia, neutropenia, thrombocytopenia was observed in 2%, 41.5%, 12% ,and 0% in 3DCRT group and in 27%, 53%, 24.5%, and 4.5% in IMRT group, respectively. Grade 2 or greater chronic anemia, leukopenia, neutropenia, and thrombocytopenia was observed in 11%, 10%, 6%, and 0% in 3DCRT group and in 11%, 9%, 4.5%, and 0% in IMRT group, respectively. LS-V30, 40; IL-V10, 20, 30, 40; LP-V10, 20 ,40; P-V10, 20, 30, 40, and TP-V10, 20, 30, 40 were significantly reduced with IMRT planning compared to 3DCRT planning. Logistic regression analysis of potential predictors showed that none of the dosimetric parameters were significant for predicting acute and chronic HT. CONCLUSION: The present findings showed that IMRT planning reduced irradiated BM volumes compared to 3DCRT planning. However, no difference between the two techniques was observed in terms of acute and chronic HT. Further studies are needed to confirm these results.

Metastatic primitive neuroectodermal tumor of the ovary in pregnancy.

Primitive neuroectodermal tumor (PNET) is a small round tumor belonging to the PNET/Ewing's sarcoma family. We hereby report a case of PNET of the ovary, which was detected at the second trimester of pregnancy. Chemotherapy was administered and a healthy baby was delivered by cesarean section. After the pregnancy, the mother was found to have metastatic disease. Chemotherapy was continued, but she died due to progressive disease 13 months after the initial diagnosis. In this case report, we discuss chemotherapy options during pregnancy and the importance of multidisciplinary approach to unusual presentations of rare tumors.

Epidural metastasis of Ewing's sarcoma: a rare localisation.

Epidural spinal metastasis of Ewing's sarcoma is rarely observed. We report on a rare case of purely epidural spinal metastasis of Ewing's sarcoma with pain and paraplegia, and describe the treatment and final outcome of the patient.

Paecilomyces variotii central nervous system infection in a patient with cancer.

Paecilomyces variotii was isolated from two subsequent cerebrospinal fluid (CSF) specimens of a cancer patient. Identification was confirmed through beta-tubulin and rDNA ITS sequencing. MICs were determined for seven antifungal agents; the isolate was found to be susceptible to amphotericin B (AMB), itraconazole (ITZ), ketaconazole (KTZ) and 5-fluorocytosine (5FC) but resistant to fluconazole (FLZ) and miconazole (MCZ). Despite antimycotic therapy, the infection proved to be fatal.

A phase I dose escalation study of high-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation (PBSCT) in patients with solid tumors and hematologic malignancies.

The purpose of this study was to determine the maximum tolerated dose of carboplatin administered with 500 mg/m2 thiotepa and 100 mg/m2 melphalan followed by autologous peripheral blood stem cell (PBSC) infusion in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose thiotepa (500 mg/m2, melphalan (100 mg/m2) and escalating doses of carboplatin 900-1500 mg/m2) followed by infusion of cryopreserved autologous PBSCs. The maximum tolerated doses were determined to be 500 mg/m2 thiotepa, 100 mg/m2 melphalan and 1350 mg/m2 carboplatin. Two consecutive patients receiving 1500 mg/m2 carboplatin experienced grade 3 mucositis and colitis. Ten patients were enrolled at the maximum tolerated dose and none had grade 3-4 regimen-related toxicity and mortality. All patients at this level experienced grade 1-2 mucositis, 90% grade 1-2 gastrointestinal toxicity, 30% grade 1-2 cardiac and renal toxicity, and 10% experienced grade 1 hepatic toxicity. The median time to achieve a granulocyte count of 0.5x10(9)/l was 9 days (range 7-12 days) and platelet count of 20x10(9)/l was 10 days (range 7-15 days). Of eight patients with stage IV refractory breast cancer, even were evaluable for response, one patient on day 75 will be evaluated soon. Five of seven (71.5%) evaluable patients achieved a complete remission (CR) and two had no response. Of seven patients with non-Hodgkin's lymphoma (n = 4) or Hodgkin's disease (n = 3), five achieved a CR (71.5%). Thiotepa, melphalan and carboplatin can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy-sensitive malignancies are warranted.

Serum erythropoietin level in anemic cancer patients.

Anemia is a frequent complication of cancer and its treatment. A defect in erythropoietin production has been advocated as being the main cause of anemia in cancer patients. We studied serum erythropoietin levels in 74 patients with solid tumors and in a control group consisting of 20 otherwise healthy individuals without any malignancy, who have only iron deficiency anemia. Serum erythropoietin levels were measured by enzyme immunoassay in cancer patients without anemia (n=34), and in anemic cancer patients (n=40); either receiving chemotherapy (n=21) or not (n=19). Anemic cancer patients were found to have decreased response of erythropoietin for a given hemoglobin level (mean, 40.1+/-34.7 u/ml), compared with the patients having only iron deficiency anemia (mean, 69.7+/-68.6 u/ml) (P<0.05). In patients with iron deficiency anemia having no malignancy, erythropoietin response was remarkably high and inversely correlated with the level of hemoglobin (r=-0.69; P=0. 05). Although there was no correlation between hemoglobin and erythropoietin response in cancer anemia (r=-0.07), serum levels of erythropoietin were found to be higher in anemic cancer patients (mean, 40.1+/-34.7 u/ml), compared with cancer patients with normal hemoglobin values (mean, 19.96+/-18.4 u/ml). There was not any statistically significant difference between erythropoietin levels in anemic cancer patients with or without chemotherapy (mean, 43. 7+/-37.7 u/ml and 41.9+/-30.08 u/ml respectively; P>0.05). No difference in serum erythropoietin levels were noted in patients treated with cisplatin or non-cisplatin containing regimens (mean, 48.36+/-33.12 u/ml and 38.55+/-43.52 u/ml, respectively; P>0.05). In this study, we demonstrated that anemia in cancer patients was caused by blunted erythropoietin response, rather than its quantitative deficiency. Serial measurements, however, should be considered in patients receiving chemotherapy.

Usefulness of the epithelial tumor marker CA-125 in non-Hodgkin's lymphoma.

CA-125, a commonly used tumor marker for epithelial ovarian cancer, is a glycoprotein found in normal tissues derived from coelomic epithelia. Increased serum levels of CA-125 have also been found in nongynecologic tumors and nonmalignant diseases involving the peritoneum. A few recent studies and sporadic case reports have reported increased CA-125 levels in patients with non-Hodgkin's lymphoma (NHL). In our study, we aimed to evaluate the serum levels of CA-125 in patients with NHL and determine its potential role to show disease activity in NHL. Serum levels of CA-125 were measured in 61 patients with NHL and were found to be correlated with clinical stage, site of involvement, and disease activity.

Anaphylaxis from intraperitoneal infusion of cisplatin: a case report.

Anaphylactic reactions to platinum compounds and paclitaxel are well-recognized complications during their systemic administration. Although there have been reports describing anaphylaxis during intravesical instillation of chemotherapeutic agents, to the best of the authors' knowledge, no hypersensitivity reactions after intraperitoneal administration of chemotherapeutic drugs has been reported in the English literature. The authors report an unusual case of anaphylaxis occurring in a 33-year-old woman who has been treated with paclitaxel and cisplatin for ovarian cancer. She developed a hypersensitivity reaction during her ninth cycle of chemotherapy, immediately after institution of intraperitoneal infusion of cisplatin. It is important to be aware of the possibility of anaphylaxis during chemotherapy administration other than the systemic route so that appropriate premedication or effective treatment can be promptly instituted.

Serum cardiolipin antibodies in cancer patients with thromboembolic events.

This study was undertaken to investigate a possible association of anticardiolipin antibodies (ACLAs) in cancer patients with thromboembolic events. Twenty-five patients with solid tumors complicated with acute thrombosis, 36 cancer patients without any thrombotic events, and a group of 20 healthy volunteers without thrombosis or malignancy were included. The mean age of the cancer patients with and without thrombosis and healthy subjects were 50 years (range 20-75), 45 years (range 23-66), and 40 years (range 20-68), respectively. Deep venous thrombosis (n = 16) and thrombosis of the central venous port-catheter systems (n = 9) were confirmed by Doppler sonography in all patients. IgG and IgM isotypes of ACLAs were quantitated by enzyme-linked immunosorbent assay with normal levels of < 23 GPL and < 11 MPL, respectively. Mean values of IgG ACLAs were found similar in cancer patients with acute thrombosis (13.8 +/- 4.9 GPL), without thrombosis (12.8 +/- 5.4 GPL) or in healthy subjects (14.8 +/- 5.5 GPL). Although the mean values of IgM ACLAs were within normal limits in all groups, cancer patients with thrombotic events had higher levels of IgM ACLAs (mean = 10.5 +/- 2.2 MPL) than cancer patients without thrombosis (mean = 4.6 +/- 2.4 MPL) (p = .01). Healthy subjects also had lower levels of IgM ACLAs (mean = 7.1 +/- 3.2 MPL) than cancer patients with thrombosis (p = .16). In addition, a higher percentage of cancer patients with or without thrombosis had IgM and IgG ACLA levels above normal limits compared with healthy controls. In conclusion, our study suggests an association between ACLAs or IgG and particularly IgM isotypes and venous thrombosis in malignancy. Identification of cancer patients who are at higher risk for developing thromboembolic events might lead to a better selection of patients for prophylactic anticoagulant therapy.