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Substantial Toxicity (substantial + toxicity)
Selected AbstractsReview of comparative studies between conventional and liposomal amphotericin B (Ambisome®) in neutropenic patients with fever of unknown origin and patients with systemic mycosisMYCOSES, Issue 9-10 2000I. W. Blau Summary Fungal infections are an important cause of morbidity and mortality in immunocompromised patients. Treatment with amphotericin B is the main therapeutic approach. However, this treatment is limited by the substantial toxicity. We present the data of the first randomized prospective comparative trial in adults (134 patients with fever of unknown origin) with conventional amphotericin B and a liposomal formulation of amphotericin B (AmBisome®, published in 1997 by Prentice et al. (Br. J. Haematol. 98, 711,718) and the data of adults with documented fungal infections (59 patients), treated in this trial. Patients received either conventional amphotericin B 1 mg kg,1 per day, liposomal amphotericin B 1 mg kg,1 per day or liposomal amphotericin B 3 mg kg,1 per day. Patients were entered if they had fever of unknown origin (FUO), defined as temperature of 38 °C or more, not responding to 96 h of systemic broad-spectrum antibiotic treatment, and neutropenia (<0.5×109 l,1). Efficacy of treatment was assessed, with success defined as resolution of fever for three consecutive days (<38 °C) in the group of patients with FUO and the freedom of clinical signs and/or the elimination of fungus in the group of patients with documented fungal infections. The safety of treatment and renal and hepatic toxicity of liposomal and conventional amphotericin B were compared. No statistically significant difference was found in the treatment efficacy in the three study arms. However, there is a tendency of better treatment results in the two groups of patients, who received liposomal amphotericin B. Thirty-five per cent of patients with documented fungal infections and 46% of patients with FUO responded to amphotericin B. In the patients group, that received 1 mg kg,1 liposomal amphotericin B it was 63 and 49%, in the group of patients that received 3 mg kg,1 liposomal amphotericin B it was 47 and 64%. Evidence of toxicity due to amphotericin B was seen in 50 patients (83%), toxicity due to liposomal amphotericin B, 1 mg kg,1, was seen in 35 patients (50%), and due to liposomal amphotericin B 3 mg kg,1 in 34 patients (54%). This was a statistically significant difference (P=0.001). It was concluded that liposomal amphotericin B was safer than conventional amphotericin B, but both formulations are equivalent in treatment efficacy. The prophylactic use of amphotericin B in these immunocompromised patients is discussed. [source] Successful Induction of Remission With Rituximab for Relapse of ANCA-Associated Vasculitis Post-Kidney Transplant: Report of Two CasesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007D. Geetha Kidney transplantation should be considered the treatment of choice for patients with end-stage renal disease due to antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). However, relapses of AAV have been reported to occur in 9,40% of cases following kidney transplantation and may adversely affect allograft outcome. These relapses are usually treated with cyclophosphamide (CYC) and glucocorticoids, but the repeated use of CYC carries a risk of substantial toxicity that may limit or prohibit its use in some patients. B lymphocytes have been implicated in the pathogenesis of AAV, and their depletion has been effective as salvage therapy for refractory disease in the nontransplant setting. We report the successful induction of remission using rituximab in two patients who suffered relapse of AAV post-kidney transplant. Given the substantial morbidity and adverse effects of CYC, rituximab appears to be a suitable alternative agent to treat relapses of AAV posttransplantation. [source] High-dose ifosfamide with mesna and granuloctye,colony-stimulating factor (recombinant human G-CSF) in patients with unresectable malignant mesotheliomaCANCER, Issue 2 2003A Southwest Oncology Group study Abstract BACKGROUND The current study was conducted to assess the activity and toxicity of high-dose ifosfamide and mesna with recombinant human granulocyte,colony-stimulating factor (rhG-CSF), given in an outpatient setting, in the treatment of patients with unresectable malignant mesothelioma. METHODS Between September 1994 and September 1996, 41 patients with histologically verified, unresectable malignant mesothelioma were registered, 38 of whom were analyzable (2 were ineligible and 1 was nonanalyzable). Patients received intravenous ifosfamide at a dose of 2.8 g/m2 over 3 hours (total dose of 14 g/m2), plus mesna at a dose of 0.56 g/m2 prior to and at 4 hours and 8 hours after ifosfamide infusion daily for 5 days every 21 days. rhG-CSF at a dose of 5 ,g/kg/day was administered subcutaneously on days 6,15. RESULTS Response assessment could be determined adequately in 21 patients. Two patients obtained responses; 1 was a confirmed partial response (3%; 95% confidence interval [95% CI], 0,14%) and 1 was an unconfirmed response (3%; 95% CI, 5,14%). Eleven patients had stable disease (29%), 7 patients developed disease progression (18%), 1 patient had an early death (3%), and 17 patients had inadequate assessment (45%). At the time of last follow-up, 36 of the 38 eligible patients had developed disease progression, with a median progression-free survival of 5 months (95% CI, 3,7 months) and 34 patients had died with a median survival of 7 months (95% CI, 6,9 months). Twenty-four patients (63%) and 7 patients (18%), respectively, had Grade (according to Southwestern Oncology Group Toxicity Criteria) 4 hematologic toxicities and Grade 4 nonhematological toxicities. There was one treatment-related death, the result of infection, pulmonary edema, and renal failure. CONCLUSIONS This regimen demonstrated a low overall objective response rate with substantial toxicity, and in the opinion of the authors does not warrant further investigation in the treatment of patients with unresectable malignant mesothelioma. Cancer 2003;98:331,6. © 2003 American Cancer Society. DOI 10.1002/cncr.11512 [source] 3465: Medical cancer therapy of lacrimal gland tumoursACTA OPHTHALMOLOGICA, Issue 2010C LE TOURNEAU Purpose The most common malignant epithelial cancer of the lacrimal gland is the adenoid cystic carcinoma (ACC). Despite a slow growth, ACCs are ultimately associated with a poor outcome. Methods Given the rarity of this disease, there are actually no conclusive recommendations for optimal therapy of this tumor. Results Surgery and postoperative radiation therapy is commonly used in the initial local treatment of ACC of the lacrimal gland. In high-risk recurrence patients, concomitant platinum-based chemoradiation should be discussed in an attempt to enhance radiosensitivity. While encouraging responses were reported with intraarterial neoadjuvant chemotherapy, this strategy was associated with substantial toxicity and should not be recommended outside of clinical trials. In the metastatic setting, systemic therapy is the only available option if no surgery and/or radiation is feasible. Although some tumour shrinkage has been reported with intravenous chemotherapy, only dismal objective response rates were achieved. Most active drugs remain anthracyclines and platinum compounds. Drug combinations do not seem to add much efficacy. More recently, non-cytotoxic molecularly targeted agents have emerged and demonstrated significant efficacy in several tumour types. These agents modulate specific targets thought to be essential for tumour proliferation and/or angiogenesis. c-KIT, PDGFR,, EGFR, and VEGFR are transmembrane receptors with oncogenic tyrosine kinase activity that are commonly overexpressed in ACC. The use of drugs triggering these targets has been disappointing so far. Conclusion The recent identification of a hallmark gene fusion transcript thought to activate critical targets involved in apoptosis, cell cycle control, cell growth and angiogenesis, heralds new treatment promise. [source] | ||||||||||