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- Use of lomustine (CCNU) in a case of cutaneous equine lymphoma. [Journal Article]
- Can Vet J 2013 Dec; 54(12):1137-41.
A 12-year-old gelding was diagnosed with recurrent lymphoma in multiple cutaneous sites. A highly invasive preputial mass caused urethral obstruction. The horse was treated with surgery and chemotherapy consisting of lomustine (CCNU) and prednisolone. The treatment was well-tolerated and effective. This is the first reported use of lomustine (CCNU) in a horse for the treatment of equine lymphoma.
- Evaluation of outcome and prognostic factors in patients of glioblastoma multiforme: A single institution experience. [Journal Article]
- J Neurosci Rural Pract 2013 Aug; 4(Suppl 1):S46-55.
We present retrospective analysis of patients of glioblastoma multiforme (GBM) and discuss clinical characteristics, various treatment protocols, survival outcomes, and prognostic factors influencing survival.From January 2002 to June 2009, 439 patients of GBM were registered in our department. The median age of patients was 50 years, 66.1% were males, and 75% underwent complete or near-total excision. We evaluated those 360 patients who received radiotherapy (RT). Radiotherapy schedule was selected depending upon pre-RT Karnofsky Performance Status (KPS). Patients with KPS < 70 (Group I, n = 48) were planned for RT dose of 30-35 Gy in 10-15 fractions, and patients with KPS ≥ 70 (Group II, n = 312) were planned for 60 Gy in 30 fractions. In group I, six patients and in group II, 89 patients received some form of chemotherapy (lomustine or temozolomide).Statistical analysis was done using Statistical Package for Social Sciences, version 12.0. Overall survival (OS) was calculated using Kaplan-Meier method, and prognostic factors were determined by log rank test. The Cox proportional hazards model was used for multivariate analysis.The median follow-up was 7.53 months. The median and 2-year survival rates were 6.33 months and 2.24% for group I and 7.97 months and 8.21% for group II patients, respectively (P = 0.001). In multivariate analysis, site of tumor (central vs. others; P = 0.006), location of tumor (parietal lobe vs. others; P = 0.003), RT dose (<60 Gy vs. 60 Gy; P = 0.0001), and use of some form of chemotherapy (P = 0.0001) were independent prognostic factors for survival.In patients with GBM, OS and prognosis remains dismal. Whenever possible, we should use concurrent and/or adjuvant chemotherapy to maximize the benefits of post-operative radiotherapy. Patients with poor performance status may be considered for hypofractionated RT schedules, which have similar median survival rates as conventional RT.
- Chemoradiation for anaplastic oligodendrogliomas: clinical outcomes and prognostic value of molecular markers. [JOURNAL ARTICLE]
- J Neurooncol 2013 Oct 26.
Combination of procarbazine, lomustine and vincristine (PCV) with radiation therapy (RT) has been associated with longer survival in patients with anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA), especially in those with chromosome 1p/19q codeletion. We report a multicenter retrospective study of 84 consecutive adult patients with AO and AOA treated with RT plus concomitant and adjuvant temozolomide (TMZ) between February 2004 and January 2011. Correlations between chromosome 1p/19q codeletion, isocitrate dehydrogenase1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. For all 84 patients the median overall survival (OS) and progression-free survival rates were 55.6 and 45.2 months, respectively. Grade 3 or 4 hematological toxicity occurred in 17 % of patients. Chromosome 1p/19q codeletion was detected in 57 %, IDH1 mutation in 63 %, and MGMT promoter methylation in 74 % of evaluable patients. In multivariate analysis the presence of chromosome 1p/19q codeletion was associated with significant survival benefit (median OS 34 months in noncodeleted tumors and not reached in codeleted tumors; HR 0.16, 95 % CI 0.03-0.45; P = 0.005). IDH1 mutation was also of prognostic significance for longer survival (P = 0.001; HR 0.20, 95 % 0.06-0.41), whereas MGMT promoter methylation was only of borderline significance. The study indicates that RT with concomitant and adjuvant TMZ is a relatively safe treatment associated with longer survival in patients with 1p/19q codeleted and IDH1 mutated tumors. Results from ongoing randomized studies will be essential to clarify if RT plus TMZ may provide survival as good as or better than RT combined with PCV for patients with AO and AOA.
- Health-related quality of life and cognitive functioning in long-term anaplastic oligodendroglioma and oligoastrocytoma survivors. [JOURNAL ARTICLE]
- J Neurooncol 2013 Oct 26.
Overall survival of patients with anaplastic oligodendroglial tumors has been improved due to the addition of procarbazine, lomustine and vincristine (PCV) chemotherapy to radiotherapy (RT), especially in 1p/19q-codeleted tumors. With improved survival, quality of survival becomes pivotal. We evaluated cognitive functioning and health-related quality of life (HRQOL) in a cohort of long-term anaplastic oligodendroglioma survivors. Thirty-two out of 37 long-term survivors included in European Organisation for Research and Treatment of Cancer (EORTC) study 26951 in the Netherlands and France participated. Cognition was assessed using neuropsychological tests for 6 domains, and HRQOL with the EORTC Quality of Life Questionnaire (EORTC QLQ-C30) and Brain Cancer Module (EORTC QLQ-BN20). Fatigue and mood were evaluated. Results were compared to healthy controls and to patients' own HRQOL 2.5 years following initial treatment. At the time of assessment, median survival for the patients was 147 months, 27 were still progression-free since initial treatment. Of progression-free patients, 26 % were not, and 30 % were severely cognitively impaired; 41 % were employed and 81 % could live independently. Patients' HRQOL was worse compared to controls, but similar to 2.5 years after initial treatment. Initial treatment (RT versus RT + PCV) was not correlated with cognition or HRQOL. In conclusion, cognitive functioning in long-term anaplastic oligodendroglioma survivors is variable. However, most patients function independently. In progression-free patients, HRQOL is relatively stable during the disease course. In this small sample, no effect of the addition of PCV on cognition or HRQOL was identified.
- Successful treatment by chemotherapy of pineal parenchymal tumor with intermediate differentiation: a case report. [Journal Article]
- Cancer Res Treat 2013 Sep; 45(3):244-9.
A 37-year-old male presented with a mass measuring 2.5 cm in size in the midbrain and obstructive hydrocephalus, which had manifested as a headache and dizziness. Magnetic resonance (MR) imaging of the brain showed intermediate enhancement on T1-weighted MR imaging and a high intensity of enhancement on T2-weighted MR. Neurosurgeons performed an occipital craniotomy with partial removal of the tumor and the postoperative diagnosis was a pineal parenchymal tumor with intermediate differentiation. He had undergone irradiation with 54 Gy of radiation on 27 fractions for removal of the remaining tumor approximately one month after surgery. However, in follow-up imaging performed four months after radiotherapy, a remnant mass in the superoposterior aspect of the midbrain was found to have extended to the hypothalamus and the third ventricle. He was treated with six cycles of procarbazine, lomustine, vincristine chemotherapy. At five months since the completion of chemotherapy, the brain MR imaging showed no evidence of any remaining tumor and he no longer displayed any of his initial symptoms.
- Life-threatening dermatologic adverse events in oncology. [JOURNAL ARTICLE]
- Anticancer Drugs 2013 Oct 8.
The incidences of life-threatening toxicities such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are inconsistently reported. The potential association of anticancer agents with SJS or TEN has not been systematically investigated. We searched the literature (Ovid: 1950 to June 2013 and PubMed: 1948 to June 2013) using terms for SJS/TEN and anticancer therapies. Primary case reports, case series, and clinical trials were included. In addition, MedWatch, the Food and Drug Administration Adverse Event Reporting System (FAERS), was searched (1968 to August 2012) for SJS/TEN reports associated with anticancer therapies. Proportional reporting ratios (PRR>2, N>3), empirical Bayes geometric mean (EBGM>2, N>3), and lower 95% confidence interval (EBGM0.05>2) were used as thresholds to constitute a signal of association between SJS/TEN and anticancer drugs. There were 46 SJS and 37 TEN cases associated with 18 and 22 anticancer drugs in the literature, respectively. Among cases in the FAERS, significant signals were associated with SJS for bendamustine and with TEN for bendamustine, busulfan, chlorambucil, fludarabine, lomustine, and procarbazine. Several drugs reported in the published literature to be associated with SJS/TEN were not found to have significant signals in FAERS. Proactive pharmacovigilance to detect and define safety signals serves to aid oncology practitioners in the recognition of possible, yet uncommon, serious, and/or life-threatening skin reactions.
- Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. [Journal Article, Research Support, Non-U.S. Gov't]
- J Clin Oncol 2013 Sep 10; 31(26):3212-8.
A randomized, phase III, placebo-controlled, partially blinded clinical trial (REGAL [Recent in in Glioblastoma Alone and With Lomustine]) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma.Patients (N = 325) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 2:2:1 to receive (1) cediranib (30 mg) monotherapy; (2) cediranib (20 mg) plus lomustine (110 mg/m(2)); (3) lomustine (110 mg/m(2)) plus a placebo. The primary end point was progression-free survival based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted magnetic resonance imaging (MRI) brain scans.The primary end point of progression-free survival (PFS) was not significantly different for either cediranib alone (hazard ratio [HR] = 1.05; 95% CI, 0.74 to 1.50; two-sided P = .90) or cediranib in combination with lomustine (HR = 0.76; 95% CI, 0.53 to 1.08; two-sided P = .16) versus lomustine based on independent or local review of postcontrast T1-weighted MRI.This study did not meet its primary end point of PFS prolongation with cediranib either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma, although cediranib showed evidence of clinical activity on some secondary end points including time to deterioration in neurologic status and corticosteroid-sparing effects.
- Pulmonary histiocytic sarcoma in a rabbit. [Journal Article]
- Vet Clin Pathol 2013 Sep; 42(3):364-7.
An approximately 8-year-old male castrated Dutch rabbit was evaluated for a 6-day history of respiratory signs, which began as sneezing and progressed to tachypnea with anorexia. On physical examination, tachypnea and pale mucous membranes were noted. Thoracic radiographs revealed a soft tissue pulmonary mass, fine-needle aspirates of which confirmed a neoplasia with malignant features suspicious for a histiocytic sarcoma. The rabbit was discharged and due to a rapidly deteriorating condition, the owner declined chemotherapy with Lomustine and elected euthanasia of the rabbit. The affected lung was submitted for histopathology. Histologic sections of the lung were characterized by clusters of histiocytic cells and multinucleated giant cells with occasional invasion of blood and lymphatic vessels. The histologic diagnosis was histiocytic sarcoma. To the authors' knowledge, this is the first case report of histiocytic sarcoma in a rabbit. Based on the clinical and radiologic findings in this case, histiocytic sarcoma should be included in the list of differentials for rabbits presenting with respiratory signs and evidence of a pulmonary mass.
- Anaplastic oligodendroglioma: a new treatment paradigm and current controversies. [Journal Article]
- Curr Treat Options Oncol 2013 Dec; 14(4):505-13.
Anaplastic oligodendroglial tumors have gained increasing interest with the emerging role of molecular markers and systemic chemotherapy during the past years. The long-term results of two landmark trials, RTOG 9402 and EORTC 26961, have resulted in a reconsideration of the appropriate therapeutic approaches for patients with these tumors. Both trials indicate that patients whose tumors harbor a 1p/19q co-deletion benefit particularly from the addition of procarbazine/lomustine (CCNU)/vincristine (PCV) chemotherapy to radiation therapy (RT). The median survival of patients with co-deleted tumors treated within the RTOG trial with PCV before irradiation was 14.7 years compared with 7.3 years of patients who received RT alone. Median overall survival has not been reached in the RT plus PCV arm of the EORTC trial, but a similar difference can be anticipated after a follow-up of more than 12 years. In contrast, no such benefit was observed for patients with tumors lacking 1p/19q co-deletion. Outside clinical trials, patients with anaplastic oligodendroglial tumors, and 1p/19q co-deletion therefore should be offered a combined treatment modality regimen, including radio- and chemotherapy. PCV, however, is associated with significant hematological toxicity and also nonhematological side effects, which probably translate into reduced quality of life for long-term survivors. Therefore, it might be warranted to replace PCV by temozolomide, which displays a more favorable side effect profile. Data from the NOA-04 study suggest that PCV and temozolomide have similar effects. However, long-term data on the benefit from temozolomide are lacking, making a definite answer on the equivalence of temozolomide and PCV in anaplastic oligodendroglioma (AO) impossible. The current evidence precludes RT alone for AO patients. Neither the RTOG nor the EORTC trial defined the role of chemotherapy alone. A comparison of combined modality treatment with chemotherapy alone followed by RT at progression is pending. Long-term follow-up of NOA-04 patients and results from future trials may help to clarify these questions. With more and more AO patients living 10 years or more, particular attention must be paid to late side effects, such as neurotoxicity, and careful monitoring is required for all treated patients.
- Current knowledge and treatment strategies for grade II gliomas. [Journal Article]
- Neurol Med Chir (Tokyo) 2013; 53(7):429-37.
World Health Organization grade II gliomas (GIIGs) include diffuse astrocytoma, oligodendroglioma, and oligoastrocytoma. GIIG is a malignant brain tumor for which the treatment outcome can still be improved. Review of previous clinical trials found the following: (1) GIIG increased in size by 3-5 mm per year when observed or treated with surgery alone; (2) after pathological diagnosis, the survival rate was increased by early aggressive tumor removal at an earlier stage compared to observation alone; (3) although the prognosis after total tumor removal was significantly better than that after partial tumor removal, half of the patients relapsed within 5 years; (4) comparing postoperative early radiotherapy (RT) and non-early RT after relapse, early RT prolonged progression-free survival (PFS) but did not affect overall survival (OS); (5) local RT of 45 to 64.8 Gy did not impact PFS or OS; (6) in patients with residual tumors, RT combined with chemotherapy (procarbazine plus lomustine plus vincristine) prolonged PFS compared with RT alone but did not affect OS; and (7) poor prognostic factors included astrocytoma, non-total tumor removal, age ≥40 years, largest tumor diameter ≥4-6 cm, tumor crossing the midline, and neurological deficit. To improve treatment outcomes, surgery with functional brain mapping or intraoperative magnetic resonance imaging or chemoradiotherapy with temozolomide is important. In this review, current knowledge regarding GIIG is described and treatment strategies are explored.