Acute infusion reactions to chemotherapeutic drugs: a single institute experience.

PURPOSE: Treating cancer often involves the use of chemotherapeutic agents. Due to the growing incidence of cancer worldwide and the expanding number of treatment options, it is important to understand the risks of adverse events associated with these treatments. In this study, we monitored the occurrence of acute infusion reactions in an outpatient chemotherapy center from April 2011 to April 2012. METHODS: For patients who developed infusion reactions, the causative drug, the dose and number of treatments received, the onset time of the reaction, the duration of the reaction, blood pressure, pulse, level of oxygen saturation during the reaction, and other symptoms were recorded. The severity of reactions was determined in accordance with NCI toxicity criteria. A reaction was considered as grade 1-2 (mild-moderate) if the patient experienced flushing, rash, fever, tremor, dyspnea, rigor, and mild hypotension. Symptoms such as severe hypotension, bronchospasm, cardiac dysfunction and anaphylaxis, requiring therapeutic intervention, were classified as severe, grade 3-4 reactions. RESULTS: Of the 2213 patients receiving chemotherapy during the study period, 138 (62%) developed an infusion reaction to the treatment. Among 138 patients most commonly treated types of carcinoma included breast (39.2%), lung (17.8%), colorectal (10%), and ovarian (8.5%) cancers. Docetaxel administration resulted in the largest number of infusion reactions, though most reactions were mild to moderate and did not require the cessation of treatment. Patients with mild to moderate reactions (89.2%) were able to continue treatment, while those who developed severe reactions (10.8%) could not continue treatment with the same agent. CONCLUSION: Although severe reactions are rare, the incidence of mild to moderate reactions against taxanes, platinum compounds, and monoclonal antibodies is quite high. Clinical symptoms do not vary widely among the agents, though the onset time of symptoms does vary. While reactions against platinum agents were of type 1 anaphylactic reactions, reactions against taxanes and monoclonal antibodies during the first infusion and in the following minutes suggest the activation of different mechanisms.

Patients with advanced cholangiocarcinoma benefit from chemotherapy if they are fit to receive it: single center experience.

PURPOSE: The purpose of this study was to report the clinical course and outcome of patients suffering from advanced cholangiocarcinoma (CCA). METHODS: The medical records of 93 patients with unresectable or metastatic CCA were retrospectively analyzed. RESULTS: Out of 93 patients, 53 (64.9%) were initially managed with palliative biliary drainage (PBD). Cisplatinbased regimens were administered to 18 (19.3%) patients, and non-cisplatin regimens (mainly 5-fluorouracil [5-FU]- based) were administered to 23 (24.8%) patients. Of all 93 patients 53 (55.9%) did not receive chemotherapy. The median overall survival (OS) for all patients was 6.1 months and was significantly higher in patients treated with chemotherapy as compared to those without chemotherapy (p=0.002). However, no difference in OS was seen in patients treated with cisplatin- or 5-FU-based chemotherapy. We noticed that a high number of patients were not referred to a medical oncologist even for advice. CONCLUSION: The relief of bile duct obstruction is an important part of the initial patient management. One of the main observations of this study was that systemic chemotherapy significantly improved survival. Increased awareness of the medical oncologists' role in the management of CCA can increase the number of patients who can have access to chemotherapy.

Severe pulmonary toxicity associated with fludarabine and possible contribution of rituximab.

Fludarabine is a nucleoside analogue used in the treatment of low-grade lymphoproliferative disorders and in conditioning regimens of non-myeloablative allogeneic stem cell transplantation. This is a relatively safe drug for clinical use but may cause side effects, some of which may be life-threatening. Here a case of severe pulmonary toxicity associated with fludarabine and a possible contribution of rituximab is presented and the literature reviewed.

Effect of colchicine on cyclosporine nephrotoxicity, reduction of TGF-beta overexpression, apoptosis, and oxidative damage: an experimental animal study.

BACKGROUND: Proinflamatory and profibrotic cytokines may be responsible for the cyclosporine A nephrotoxicity. Increased levels of apoptosis, free oxygen redicals, and transforming growth factor beta (TGF-beta), may play an important roles in the pathogenesis of nephrotoxicity. In this experimental animal study, we sought to investigate the effects of colchicine on the cyclosporine nephrotoxicity. METHOD: Twenty-four Wistar albino rats were divided into three groups: cyclosporine 15 mg/kg subcutaneously (SC); cyclosporine 15 mg/kg SC plus colchicine 30 mcg/kg orally; and a control group; equal doses of olive oil orally were administered to groups 1, 2, and 3. Renal function, cyclosporine levels, and serum malonyldialdehyde (MDA) levels were measured at the end of 4 weeks. Apoptosis, TGF-beta, and other findings were detected in renal tissue with the TUNEL method, with a immunohistochemical method, and with routine staining procedures, respectively. RESULTS: There were significant differences in the values of mean creatinine clearance between group 1 and group 3 and between group 2 and group 3 (P < .05 for each comparison), but not between group 1 and group 2 (P > .05). MDA levels in group 1 were high compared with the control group (P < .05) with a trend toward elevation relative to group 2 but the results were not statistically significant (P > .05). Renal tubular vacuolization in group 1 and group 2 animal were greater than in the control group, but no significant difference were observed between any of the groups (P > .05). Mononuclear cell infiltration in group 1 and group 2 hosts were higher than the control group, but there was no significant differences between the groups (P > .05). Afferent arteriolar hyalinization was observed group 1 and 2 but not group 3. There was a statistically significant difference between group 1 and group 3 and between group 2 and group 3 (P < .05 for each comparison). The expression level of TGF-beta was higher in group 1 than group 2 or group 3 (P <.05 for each comparison) but group 2 and group 3 were similar (P > .05). Apoptotic cell death count of group 1 was higher than that in group 2 or group 3 (P < .05, for each comparison); moreover, group 2 also showed greater numbers of apoptotic cells than group 3 (P < .001). At the end of the 4 weeks, there was no intersititial fibrosis in any of the hosts. CONCLUSION: While cyclosporine caused increased TGF-beta expression and apoptotic cell death in the renal tissue of rats colchicine prevented the increase in MDA serum levels, TGF-beta expression, and apoptosis in renal tissue. Our study suggests that colchicine may diminish the cyclosporine nephrotoxicity by its suppressing the expression of TGF-beta, apoptotic cell death, and MDA production.

Survivin and aven: two distinct antiapoptotic signals in acute leukemias.

BACKGROUND: Antiapoptotic signals are important in the development, progression and prognosis of malignant tumors. The aim of this study was to determine the two distinct antiapoptotic signals-survivin and aven-in acute leukemias and compare them with clinical and hematological findings and response to therapy. Real-time quantitative PCR was used and survivin and aven were detected at the messenger (m)RNA level. PATIENTS AND METHODS: Sixty-five patients with acute leukemia [37 with acute myeloblastic leukemia (AML) and 28 with acute lymphoblastic leukemia (ALL)] were used as the study group and 10 healthy subjects were used as the control group. RESULTS: Survivin was between 0.0 and 0.829 copy number/cell (median 0.0721, mean 0.5424301909 +/- 0.139799488589) and aven was between 0.0 and 0.853 copy number/cell (median 0.0124, mean 0.070335542 +/- 0.1524685709). We found an important association between survivin and aven (P = 0.000). Both survivin and aven were higher in the study group than in the controls (P = 0.001 and 0.035, respectively). When we compared survivin and aven with other clinical and hematological parameters, there was an important association between survivin and extramedullary involvement (P = 0.033), survivin and alkaline phosphatase (P = 0.06), white blood cell (WBC) count and lactate dehydrogenase (LDH) (P = 0.000), WBC count and uric acid (P = 0.074), hemoglobin level and LDH (P = 0.072), LDH and uric acid (P = 0.057), CD7 expression and survivin (P = 0.097), and CD34 expression and aven (P = 0.058). Response to therapy was evaluated according to the survivin and aven levels. Survivin level was lower in refractory patients as compared with complete responders (P = 0.085). Aven level was higher in patients with relapse as compared with non-relapse patients (P = 0.04). There was no important association between survivin or aven and performance status, lymphadenopathy or organomegaly. CONCLUSIONS: Both survivin and aven are important antiapoptotic signals in acute leukemias, and the association between extramedullary involvement, CD7 expression and CD34 expression, which are important poor prognostic indicators in acute leukemias, suggests that survivin and/or aven may be novel prognostic indicators in acute leukemias. Further studies with a higher number of patients will be more informative.