@article{page_mcentee_williams_george_price_novotney_hauck_riviere_dewhirst_thrall_1994, title={EFFECT OF WHOLE-BODY HYPERTHERMIA ON CARBOPLATIN DISPOSITION AND TOXICITY IN DOGS}, volume={10}, ISSN={["0265-6736"]}, DOI={10.3109/02656739409012373}, abstractNote={Fifty dogs with refractory or disseminated spontaneous tumours were evaluated in two independent phase I studies using either carboplatin (CBDCA) alone or CBDCA plus whole body hyperthermia (WBH). CBDCA was administered as a 30 min infusion at the onset of the plateau phase of WBH in dogs receiving combined treatment. Serum samples were collected and drug disposition was determined in both treatment groups. The dose-effect relationship was mathematically described with a logistic regression model developed from categorical toxicity data accumulated throughout the first two treatment courses in all dogs. The maximum tolerated dose (MTD) was defined as that dose which resulted in a 50% probability of achieving moderate or severe toxicity. The only toxicities observed were neutropenia and thrombocytopenia, which were dose-dependent. The nadir occurred between 7 and 14 days following treatment. A significant decrease in the area under the serum CBDCA versus time curve for dogs undergoing WBH was consistent with increased tissue binding of the drug as well as increased urinary eliminations. Serum AUC values determined following the first course of treatment were predictive of subsequent toxicity in both treatment groups. The MTD (95%CI) for CBDCA and CBDCA/WBH were estimated to be 318(44) and 239(51) mg/M2 respectively (p = 0.08). A randomized phase II evaluation should be initiated to determine if a therapeutic gain can be achieved using combined CBDCA and WBH. Further refinement of the CBDCA dose in such a trial should be based on both pharmacokinetic parameters and normal tissue response.}, number={6}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={PAGE, RL and MCENTEE, MC and WILLIAMS, PL and GEORGE, SL and PRICE, GS and NOVOTNEY, CA and HAUCK, ML and RIVIERE, JE and DEWHIRST, MW and THRALL, DE}, year={1994}, pages={807–816} }
 @article{novotney_page_macy_dewhirst_ogilvie_withrow_mcentee_heidner_allen_thrall_et al._1992, title={PHASE-I EVALUATION OF DOXORUBICIN AND WHOLE-BODY HYPERTHERMIA IN DOGS WITH LYMPHOMA}, volume={6}, ISSN={["0891-6640"]}, DOI={10.1111/j.1939-1676.1992.tb00346.x}, abstractNote={Fifteen previously untreated dogs with histologically confirmed, high‐grade multicentric lymphoma were entered into a phase I study to evaluate combined doxorubicin and whole‐body hyperthermia (DOX/ WBH). Groups of three, four, and eight dogs were treated with whole‐body hyperthermia and concurrent doxorubicin at 12 mg/m2, 24 mg/m2 and 30 mg/m2, respectively, after one doxorubicin induction dose at 30 mg/m2. Plateau temperature (42 ± 0.1d̀C) was maintained for 90 minutes using a radiant heating device. A total of five DOX/WBH treatments per dog were planned, and these were given every 21 days. Treatment‐related toxicity was not seen in the 12‐mg/m2 doxorubicin dose group. Tumor progression prohibited administration of more than three DOX/WBH treatments to any dog in the 12‐mg/m2 group. Premature ventricular contractions developed after the fifth treatment in one of the four dogs treated with 24 mg/m2 of doxorubicin. Two dogs (25%) in the 30‐mg/m2 dose group had treatment‐related toxicity. One dog experienced acute serious myelosuppression 1week after the third treatment. This dog received all planned DOX/WBH treatments. Asymptomatic cardiac toxicosis consisting of decreased ejection fraction and fractional shortening developed in the second dog. This dog received only two DOX/WBH treatments. The three dogs treated at 12 mg/m2 had partial responses of short duration (60–83 days). Four dogs treated at 24 mg/m2 had complete responses for 150,164,186, and 200 days. Eight dogs treated at 30 mg/m2 had complete responses with a mean and median duration of 241 and 190 days, respectively. It was concluded that after a single induction doxorubicin treatment at 30 mg/m2, five additional doses of doxorubicin at 30 mg/m2 can be administered without serious toxicity under hyperthermic conditions. Thus, there is no requisite doxorubicin dose reduction under hyperthermic conditions in comparison to the amount of doxorubicin normally given to dogs. Prospective evaluation of the efficacy of combined doxorubicin (at 30 mg/m2) and whole‐body hyperthermia compared with doxorubicin alone in dogs with lymphoma is warranted. (Journal of Veterinary Internal Medicine 1992; 6:245–249)}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={NOVOTNEY, CA and PAGE, RL and MACY, DW and DEWHIRST, MW and OGILVIE, GK and WITHROW, SJ and MCENTEE, MC and HEIDNER, GL and ALLEN, SA and THRALL, DE and et al.}, year={1992}, pages={245–249} }
 @article{novotney_english_housman_davidson_nasisse_jeng_davis_tompkins_1990, title={LYMPHOCYTE POPULATION-CHANGES IN CATS NATURALLY INFECTED WITH FELINE IMMUNODEFICIENCY VIRUS}, volume={4}, ISSN={["1473-5571"]}, DOI={10.1097/00002030-199012000-00005}, abstractNote={Feline immunodeficiency virus (FIV) is associated with feline acquired immunodeficiency syndrome (FAIDS) and has been suggested as a model for HIV-induced human AIDS. The most obvious immunological defect in HIV infection is a reduction in CD4+ cell numbers and an inversion of the CD4:CD8 ratio. To determine whether the same is true in FIV infection, we analyzed by flow cytometry using a panel of monoclonal antibodies to feline lymphocyte populations the CD4:CD8 ratios in cats naturally infected with the virus. We report that 13 of 19 FIV-infected cats had ratios below the 5th percentile of normal cats (0.57, established from analysis of 39 normal cats) and 18 of 19 had ratios below 1. Repeated analyses over a period of several months revealed the inverted ratios to be consistent. Analysis of lymphocyte numbers in FIV-infected cats shows that the inverted ratios are due to a decrease in CD4+ T cells, while CD8+ T and B cells remain relatively normal in number. Analysis of a group of cats with a variety of other chronic diseases, including feline leukemia virus (FeLV) infections, revealed a near-normal distribution of CD4:CD8 ratios. These findings are similar to those in HIV infections and indicate that, like HIV, FIV causes a selective reduction in CD4+ cells and should be an excellent model for studying retrovirus-induced AIDS.}, number={12}, journal={AIDS}, author={NOVOTNEY, C and ENGLISH, RV and HOUSMAN, J and DAVIDSON, MG and NASISSE, MP and JENG, CR and DAVIS, WC and TOMPKINS, MB}, year={1990}, month={Dec}, pages={1213–1218} }