4,081 research outputs found

    Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.

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    BackgroundCompounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products.Hypothesis/objectivesThe initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies.AnimalsThirty-seven dogs treated with FDA-approved or compounded lomustine.MethodsDogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection.ResultsTwenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration.Conclusions and clinical importanceThese data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products

    Pulse-Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs.

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    BackgroundNonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy.Hypothesis/objectivesThe primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse-administered toceranib phosphate (TOC) combined with lomustine.AnimalsForty-seven client-owned dogs with measurable MCT.MethodsToceranib phosphate was given PO on days 1, 3 and 5 of a 21-day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m(2) . All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone.ResultsThe MTD of lomustine was established at 50 mg/m(2) when combined with pulse-administered TOC; the dose-limiting toxicity was neutropenia. Forty-one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression-free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy.Conclusions and clinical importanceCombined treatment with pulse-administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT

    Procarbazine, CCNU and vincristine (PCV) versus temozolomide chemotherapy for patients with low-grade glioma: a systematic review.

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    Low-grade gliomas (LGG) encompass a heterogeneous group of tumors that are clinically, histologically and molecularly diverse. Treatment decisions for patients with LGG are directed toward improving upon the natural history while limiting treatment-associated toxiceffects. Recent evidence has documented a utility for adjuvant chemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) or temozolomide (TMZ). We sought to determine the comparative utility of PCV and TMZ for patients with LGG, particularly in context of molecular subtype. A literature search of PubMed was conducted to identify studies reporting patient response to PCV, TMZ, or a combination of chemotherapy and radiation therapy (RT). Eligibility criteria included patients 16 years of age and older, notation of LGG subtype, and report of progression-free survival (PFS), overall survival (OS), and treatment course. Level I, II, and III data were included. Adjuvant therapy with PCV resulted in prolonged PFS and OS in patients with newly diagnosed high-risk LGG. This benefit was accrued most significantly by patients with tumors harboring 1p/19q codeletion and IDH1 mutation. Adjuvant therapy with temozolomide was associated with lower toxicity than therapy with PCV. In patients with LGG with an unfavorable natural history, such as with intact 1p/19q and wild-type IDH1, RT/TMZ plus adjuvant TMZ may be the best option. Patients with biologically favorable high-risk LGG are likely to derive the most benefit from RT and adjuvant PCV

    Tumour volume response, initial cell kill and cellular repopulation in B16 melanoma treated with cyclophosphamide and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

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    The relationship between tumour volume response and cell kill in B16 melanoma following treatment in vivo with cyclophosphamide (CY) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was investigated. Tumour volume response, expressed as growth delay, was estimated from measurements of tumour dimensions. Depression of in vitro colony-forming ability of cells from treated tumours was used as the measure of tumour cell kill. The relationship between these parameters was clearly different for the two agents studied. CY produced more growth delay (7.5 days) per decade of tumour cell kill than CCNU (2 to 3.5 days). The possibility that this was due to a technical artefact was rejected in favour of an alternative explanation that different rates of cellular repopulation in tumours treated with CY and CCNU might be responsible. Cellular repopulation was measured directly, by performing cell-survival assays at various times after treatment with doses of CY and CCNU which produced about 3 decades of cell kill. The rate of repopulation by clonogenic cells was much slower after treatment with CY than with CCNU, and this appears to account for the longer duration of the growth delay obtained with CY
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