e18112 Background: Lung cancer is the leading cause of cancer death worldwide and the majority of patients present with locally advanced or metastatic disease. Novel treatment regimens combining multikinase inhibitors with platinum-based chemotherapy may increase efficacy without additional toxicity. Methods: 12 patients (median age 62 yrs (44-77); 4/12 females; 7/12 ECOG 0) with untreated NSCLC (UICC6 stage IIIB with pleural effusion and IV; 7/12 non-squamous cell histology) were enrolled in a phase I dose escalation trial and received sorafenib 200mg bid (n = 3) to 400 mg bid (n = 9) d2-d19 following pemetrexed 500 mg/m2 d1 and carboplatin AUC6 d1. The primary endpoint was to determine the recommended sorafenib dose, secondary endpoints were safety, toxicity and efficacy. Results: 52treatment cycles were applied. 11/12 patients experienced CTCAE grade 3/4 hematotoxicity (83% thrombocytopenia, 83% neutropenia, 92% leucopenia) requiring one (n = 2) or two dose reductions (n = 7). The majority of dose reductions were caused by grade 3/4 thrombocytopenia (82%). 4/7 patients were withdrawn from the trial after experiencing grade 3/4 thrombocytopenia in three consecutive cycles despite two dose reductions. Other grade 3/4 adverse events were infrequent (25%). Best responses were PR in 3 patients (25%), SD in 8 patients (67%), and PD in 1 patient (8%). Median PFS was 6.3 months (95%CI 3.7-8.9) and median OS was 14.7 months (6.8-22.6). Results do not differ among the sorafenib dose cohorts (200 mg bid vs. 400 mg bid) and among histology (squamous vs. non-squamous NSCLC) (p > 0.1, all comparisons). Conclusions: Both in squamous and non-squamous metastatic NSCLC, the combination of sorafenib with pemetrexed-carboplatin was active and safe except for hematotoxicity. Sorafenib administered in this combination appears to enhance thrombocytopenia compared to historical data. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Advisory Board Member

The three-dimensional (3D) weaving process offers the ability to tailor the mechanical properties via design of the weave architecture. One repeat of the 3D woven fabric is represented by the unit cell. The model accepts basic weaver and material manufacturer data as inputs in order to calculate the geometric characteristics of the 3D woven unit cell. The specific weave architecture manufactured and subsequently modelled had an angle interlock type binding configuration. The modelled result was shown to have a close approximation compared to the experimentally measured values and highlighted the importance of the representation of the binder tow path.

ABSTRACT The combination of liposomal amphotericin B (LAMB) and caspofungin (CAS) holds promise to improve the outcome of opportunistic invasive mycoses with poor prognosis. Little is known, however, about the safety and pharmacokinetics of the combination in patients at high risk for these infections. The safety and pharmacokinetics of the combination of LAMB and CAS were investigated in a risk-stratified, randomized, multicenter phase II clinical trial in 55 adult allogeneic hematopoietic stem cell recipients (aHSCT) with granulocytopenia and refractory fever. The patients received either CAS (50 mg/day; day 1, 70 mg), LAMB (3 mg/kg of body weight/day), or the combination of both (CASLAMB) until defervescence and granulocyte recovery. Safety, development of invasive fungal infections, and survival were assessed through day 14 after the end of therapy. Pharmacokinetic sampling and analysis were performed on days 1 and 4. All three regimens were well tolerated. Premature study drug discontinuations due to grade III/IV adverse events occurred in 1/18, 2/20, and 0/17 patients randomized to CAS, LAMB, and CASLAMB, respectively. Adverse events not leading to study drug discontinuation were frequent but similar across cohorts, except for a higher frequency of hypokalemia with CASLAMB ( P < 0.05). Drug exposures were similar for patients receiving combination therapy and those randomized to monotherapy. There was no apparent difference in the occurrence of proven/probable invasive fungal infections and survival through day 14 after the end of therapy. CASLAMB combination therapy in immunocompromised aHSCT patients was as safe as monotherapy with CAS or LAMB and had similar plasma pharmacokinetics, lending support to further investigations of the combination in the management of patients with invasive opportunistic mycoses.

ABSTRACT Liposomal amphotericin B (LAMB) and caspofungin (CAS) are important antifungal agents in allogeneic hematopoietic stem cell transplant (aHSCT) recipients. Little is known, however, about the pharmacokinetics (PK) of both agents and their combination in this population. The PK of LAMB and CAS and the potential for PK interactions between both agents were investigated within a risk-stratified, randomized phase II clinical trial in 53 adult aHSCT recipients with granulocytopenia and refractory fever. Patients received either LAMB ( n = 17; 3 mg/kg once a day [QD]), CAS ( n = 19; 50 mg QD; day 1, 70 mg), or the combination of both (CAS-LAMB; n = 17) for a median duration of 10 to 13 days (range, 4 to 28 days) until defervescence and granulocyte recovery. PK sampling was performed on days 1 and 4. Drug concentrations in plasma (LAMB, 405 samples; CAS, 458 samples) were quantified by high-pressure liquid chromatography and were analyzed using population pharmacokinetic modeling. CAS concentration data best fitted a two-compartment model with a proportional error model and interindividual variability (IIV) for clearance (CL) and central volume of distribution ( V 1 ) (CL, 0.462 liter/h ± 25%; V 1 , 8.33 liters ± 29%; intercompartmental clearance [ Q ], 1.25 liters/h; peripheral volume of distribution [ V 2 ], 3.59 liters). Concentration data for LAMB best fitted a two-compartment model with a proportional error model and IIV for all parameters (CL, 1.22 liters/h ± 64%; V 1 , 19.2 liters ± 38%; Q , 2.18 liters/h ± 47%; V 2 , 52.8 liters ± 84%). Internal model validation showed predictability and robustness of both models. None of the covariates tested (LAMB or CAS comedication, gender, body weight, age, body surface area, serum bilirubin, and creatinine clearance) further improved the models. In summary, the disposition of LAMB and CAS was best described by two-compartment models. Drug exposures in aHSCT patients were comparable to those in other populations, and no PK interactions were observed between the two compounds.

Diphtheria Studies: I—The Significance of the Schick Test in the Adult C. C. Young, W. E. Bunney, Minna Crooks, G. D. Cummings, and F. C. Forsbeck CopyRight*Read before the Epidemiology Section of the American Public Health Association at the Sixty-second Annual Meeting in Indianapolis, Ind., October 9, 1933. https://doi.org/10.2105/AJPH.24.8.835 Published Online: August 29, 2011

Laboratory The Deteriroration of Iodized Salt C. C. Young, and M. Starr Nichols CopyRight https://doi.org/10.2105/AJPH.19.8.923 Published Online: August 29, 2011

LABORATORY A SIMPLIFIED PROCEDURE IN DETERMINING B. COLI IN WATER (PRESUMPTIVE TEST) C. C. Young, and William Litterer CopyRight https://doi.org/10.2105/AJPH.18.4.491 Published Online: August 29, 2011

LABORATORY THE PREPARATION AND STANDARDIZATION OF TUBERCULIN C. C. Young, and Esmond R. Long CopyRight https://doi.org/10.2105/AJPH.16.10.1046 Published Online: August 30, 2011

LABORATORY HYPERIMMUNIZATION BY MEANS OF DIPTHERIA ANATOXIN * Affiliation C. C. Young, and B. Feierabend CopyRight*Published through the kindness of Mr. Williamson of the Information Service of the Rockefeller Foundation. https://doi.org/10.2105/AJPH.16.6.643 Published Online: August 30, 2011

LABORATORY A BLOOD AGAR PLATE COUNTING APPARATUS C. C. Young, and M. E. Parker, Technologist CopyRight https://doi.org/10.2105/AJPH.16.5.532-a Published Online: August 30, 2011

Swabs and cultures prove to be of equal value for diphtheria diagnosis while swabs may give evidence of other infections. This paper tells of an experiment in routine work lasting a year. It shows swabs to be less costly, never dry through storage, and better for surveys. The paper emphasizes the need of rural branch laboratories.

Elect) FELIXJ. UNDERWOOD, M.D.,Jackson, Miss.(Presi- dent)