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Study Objective Variable metabolism, dose-dependent efficacy, and a narrow therapeutic target of cyclophosphamide ( CY) suggest that dosing based on individual pharmacokinetics ( PK) will improve efficacy and minimize toxicity. Real-time individualized CY dose adjustment was previously explored using a maximum a posteriori ( MAP) approach based on a five serum- PK sampling in patients with hematologic malignancy undergoing stem cell transplantation. The MAP approach resulted in an improved toxicity profile without sacrificing efficacy. However, extensive PK sampling is costly and not generally applicable in the clinic. We hypothesize that the assumption- free Bayesian approach ( AFBA) can reduce sampling requirements, while improving the accuracy of results. Design Retrospective analysis of previously published CY PK data from 20 patients undergoing stem cell transplantation. In that study, Bayesian estimation based on the MAP approach of individual PK parameters was accomplished to predict individualized day-2 doses of CY. Based on these data, we used the AFBA to select the optimal sampling schedule and compare the projected probability of achieving the therapeutic end points. Measurements and Main Results By optimizing the sampling schedule with the AFBA, an effective individualized PK characterization can be obtained with only two blood draws at 4 and 16 hours after administration on day 1. The second-day doses selected with the AFBA were significantly different than the MAP approach and averaged 37% higher probability of attaining the therapeutic targets. Conclusions The AFBA, based on cutting-edge statistical and mathematical tools, allows an accurate individualized dosing of CY, with simplified PK sampling. This highly accessible approach holds great promise for improving efficacy, reducing toxicities, and lowering treatment costs. [ABSTRACT FROM AUTHOR]

Study Objective To demonstrate the premise of individualized dosing charts ( IDCs) as a clinical-bedside decision-support tool to individualize dosage regimens for drugs in which the interpatient variability is controlled by the pharmacokinetic ( PK) behavior of the patient, to calculate the optimal sampling schedule (OSS), which minimizes the number of blood samples per patient. The approach is illustrated with available PK data for gabapentin. Design Retrospective proof of principles study using gabapentin PK data from a published clinical trial. Patients Nineteen subjects in a trial designed to uncover the importance of the genetic contributions to variability in gabapentin absorption, renal elimination, and transport; subjects were monitored for 36 hours after administration of a single dose of gabapentin 400 mg, and plasma concentrations were determined at 14 time points. Measurements and Main Results When the PK profiles were different between subjects, the IDCs are dramatically different from each other and from the IDC for an 'average' patient representing the patient population. The dose amount and dosing interval must be adjusted to maximize the probability of staying within the target concentration range. An optimal sampling methodology based on the assumption-free Bayesian approach is used to distinguish the PK profile of an individual patient from the patient population. In the case of gabapentin, only two optimally selected test blood samples, at 1.5 and 6 hours after administration of a single doses, were necessary. The average sensitivity and the average specificity of the OSS was 99% and 96%, respectively. Conclusion IDCs display the risk of a patient violating the target concentration range for any dosage regimen. They can be used as a clinical-bedside decision-support tool in a patient-physician partnership to decide on a dose amount and dosing interval that are medically acceptable while practical and convenient to ensure compliance. By using the assumption-free Bayesian approach and the OSS, the number of samples required from a new patient to individualize the dosage regimen can be reduced significantly while preserving high levels of sensitivity and specificity. Prospective studies are being planned to validate the encouraging results. This approach can be extended to any drug if PK data and a target concentration range are available for either therapeutic drug monitoring or target concentration intervention. [ABSTRACT FROM AUTHOR]

BACKGROUND: Venous thromboembolism (VTE) is a significant but poorly understood complication in patients with newly diagnosed multiple myeloma (NDMM). As a result, most patients receive thromboprophylaxis with low molecular weight heparin (LMWH). The purpose of this retrospective study was to identify risk factors for VTE in NDMM and evaluate the effectiveness of LMWH. METHODS: A total of 604 patients with newly diagnosed myeloma completed 3 induction cycles with multiagent chemotherapy with up-front randomization to thalidomide between 1998 and 2004. Prophylactic enoxaparin was given to thalidomide recipients beginning in June 2001, and 122 subjects received prophylactic epoetin alfa (EPO) as part of an exercise trial. The primary study endpoint was grades 3-4 VTE. RESULTS: A total of 72 patients (11.9%) developed VTE (mostly deep venous thrombosis), with a higher incidence among EPO recipients ( P = .001), although only significant for upper extremity DVT ( P = .0002). The EPO-treated patients had higher hemoglobin (Hb) levels throughout the study ( P < .0005), although no relationship between higher Hb levels and increasing incidence of VTE could be shown. A history of VTE was a strong predictor of VTE on univariate analysis ( P < .000005). Enoxaparin did not reduce the rate of VTE ( P = .158). Logistic regression analysis identified thalidomide therapy ( P = .001; odds ratio [OR], 2.428; 95% confidence interval [CI], 1.418-4.159) and prophylactic EPO ( P = .002; OR, 2.488; 95% CI, 1.432-4.324) as risk factors for VTE. Myeloma response and survival were not negatively affected by prophylactic EPO or VTE. CONCLUSIONS: Prophylactic EPO, thalidomide therapy, and VTE history, but not higher Hb levels, were found to increase the risk of VTE among NDMM patients receiving multiagent chemotherapy. This risk was not found to be reduced in this population by LMWH thromboprophylaxis. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lower alimentary tract mucositis is a serious complication of chemotherapy. The aim of the study was to determine the incidence, risk factors, and mortality of lower alimentary tract mucositis in a homogeneous population of patients with newly diagnosed myeloma receiving similar antineoplastic therapy and standardized supportive care. METHODS: Lower alimentary tract mucositis was evaluated among 303 consecutive patients with myeloma (2004-2007) enrolled in a clinical trial consisting of induction chemotherapy, tandem melphalan-based autologous stem cell transplantation (ASCT), and consolidation. Lower alimentary tract mucositis was defined as neutropenia- associated grade II-IV enteritis/colitis. Pretreatment risk factors were examined including body surface area (BSA), serum albumin (albumin), and estimated creatinine clearance (CrCl). Multiple logistic regression model was used to compute adjusted odds ratio (OR) and 95% confidence intervals (CI). RESULTS: Forty-seven (15.5%) patients developed lower alimentary tract mucositis during 1529 courses of chemotherapy (including 536 melphalan-based ASCT). Pre-enrollment BSA <2 m² (OR, 2.768; 95% CI, 1.200-6.381; P = .0169) increased the risk for lower alimentary tract mucositis, whereas higher albumin was protective (OR, 0.698; 95% CI, 0.519-0.940; P = .0177). Pretransplant variables associated with lower alimentary tract mucositis were BSA <2 m² (OR, 4.451; 95% CI, 1.459-13.58, P = .0087) and estimated CrCl <60 mL/min (OR, 3.493; 95% CI, 1.173-10.40; P = .0246). Higher albumin level conferred protection (OR, 0.500; 95% CI, 0.304-0.820; P = .0061). No lower alimentary tract mucositis-related death was observed. CONCLUSIONS: Lower alimentary tract mucositis is not uncommon among a homogenous population of oncology patients undergoing sequential courses of chemotherapy including melphalan-based ASCT but does not contribute to mortality. Lower BSA, renal function, and albumin are associated with increased risk for lower alimentary tract mucositis. [ABSTRACT FROM AUTHOR]

The article discusses a study concerning the immune reconstitution inflammatory syndrome (IRIS) in cancer patients with pulmonary aspergillosis recovering from neutropenia. Under the study, galactomannan, an Aspergillus-specific polysaccharide released during aspergillosis, was used to determine IRIS responses from progressive aspergillosis. Results show that deterioration corresponded with microbiologic response. It concludes that declining galactomannan values suggest IRIS with an aspergillus response.

Background: Over the past year at least 10 case series and several case reports on osteonecrosis of the jaw (ONJ) have been published with most found in the oral surgery literature. This clinical entity is largely unknown to head and neck surgeons. Methods: Retrospective chart review. Results: A total of 479 charts were reviewed, identifying 25 individuals meeting inclusion criteria. Mean age was 63.4 (standard deviation, 9.9) years; 40% were female. Multiple myeloma was the most common comorbidity. Twenty-five patients were treated with bisphosphonates for 4.4 years (range, 1 to 8 years); most commonly pamidronate before ONJ diagnosis. Forty-two percent (10) took steroids within the month before diagnosis. Fifty-two percent (11) underwent dental work before developing ONJ. Conclusion: These data reflect the importance of awareness of the possibility of ONJ with bisphosphonate therapy. [Copyright &y& Elsevier]

Two fatal cases of rhinocerebral mucormycosis with fungal invasion and occlusion of the internal carotid artery are described. Review of the literature reveals 35 similar cases of whom only 6 survived. Emphasis is placed on the need for early diagnosis and prompt therapy which consists of correction of the underlying disease, aggressive surgical debridement, and amphotericin B. [ABSTRACT FROM AUTHOR]