@article{williams_johnson_hauck_ruslander_price_thrall_2004, title={Chemotherapy followed by half-body radiation therapy for canine lymphoma}, volume={18}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2004)18<703:CFBHRT>2.0.CO;2}, abstractNote={A protocol of induction chemotherapy followed by half-body radiation therapy for treatment of lymphoma was used in 94 dogs. Seventy-three (78%) dogs achieved complete remission. Substage (P = .011) and phenotype (P = .015) were identified as predictors of complete remission rate. Of these, 52 dogs received half-body irradiation. Cranial and caudal halves received a total dose of 8.0 Gy, given in 2 fractions of 4.0 Gy on consecutive days with cobalt-60 photons and a 3-week interval between halves. Median 1st remission for these dogs was 311 days. Anemia was identified as the only predictor for length of 1st remission (P = .024). Toxicoses after half-body irradiation generally were mild and infrequent and included myelosuppression and gastrointestinal signs. Thirty-one dogs relapsed and 20 resumed treatment with induction followed by maintenance chemotherapy. Seventeen (85%) dogs achieved a 2nd complete remission. Median overall remission for all 52 dogs was 486 days. Results of this study suggest that half-body radiation therapy after induction chemotherapy is well tolerated and might increase remission duration compared with conventional protocols that use chemotherapy alone, but this increase might not be long enough to be clinically relevant or to justify application of the method described herein.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Williams, LE and Johnson, JL and Hauck, ML and Ruslander, DM and Price, GS and Thrall, DE}, year={2004}, pages={703–709} }
 @article{proulx_ruslander_dodge_hauck_williams_horn_price_thrall_2003, title={A retrospective analysis of 140 dogs with oral melanoma treated with external beam radiation}, volume={44}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2003.tb00468.x}, abstractNote={Despite the early notion that canine oral malignant melanoma is radioresistant, recent data suggest that external beam radiotherapy is effective in local tumor control. However, optimal fractionation schedules have not been established. The high rate of regional and distant metastasis is another problem that has hindered long‐term control. The role of chemotherapy in the management of canine oral melanoma has also not been determined. In this study, data from 140 dogs irradiated at North Carolina State University were evaluated with the following objectives: (1) to compare the efficacy of three radiation therapy protocols (36 Gy, 9 Gy × 4 fractions; 30 Gy, 10 Gy × 3 fractions; or >45 Gy, 2–4 Gy × 12–19 fractions) for the treatment of dogs with oral malignant melanoma, (2) to identify any host or tumor factors influencing prognosis, and (3) to determine the impact of systemic chemotherapy on treatment outcome. Information regarding response to therapy, disease progression, and survival were determined from the medical records or from information obtained by telephone or mail survey. Relationships between host, tumor, and treatment variables and outcome measures (response, time to first event, and survival) were evaluated using Fisher's exact test (response) and the Cox regression model (time to first event and survival). The median time to first event for the 140 dogs was 5.0 months (95% C.I., 4–6 months) and the median survival was 7.0 months (95% C.I., 6–9 months). In the univariate analysis, the following variables were associated with increased time to first event and survival: (1) rostral tumor sublocation; (2) lack of bone lysis observed on skull imaging, and (3) microscopic tumor burden. In a multivariate analysis of 111 dogs with complete data for these variables, tumor sublocation, bone lysis, and tumor volume were identified as joint predictors of time to first event (p<.001,p<.001, andp= .04, respectively) and survival (p<.001,p<.001, andp= 05, respectively). There were no differences in response, time to first event and survival between the three radiation therapy protocols used. Systemic chemotherapy had no impact on the development of metastatic disease, time to first event, or survival, although the dosages used in this study were suboptimal. External beam radiation therapy is effective in local disease control of canine oral malignant melanoma; however, the optimal fractionation scheme has yet to be determined. The high metastatic rate observed with this disease and the inefficacy of systemic chemotherapy indicate that further investigation into novel therapies is warranted.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Proulx, DR and Ruslander, DM and Dodge, RK and Hauck, ML and Williams, LE and Horn, B and Price, GS and Thrall, DE}, year={2003}, pages={352–359} }
 @article{kobayashi_hauck_dodge_page_price_williams_hardie_mathews_thrall_2002, title={Preoperative radiotherapy for vaccine associated sarcoma in 92 cats}, volume={43}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2002.tb01036.x}, abstractNote={Medical records for 92 cats with a vaccine associated sarcoma receiving preoperative irradiation, with or without chemotherapy, between December 1985 and September 1998 were reviewed. The purposes were to quantify response to treatment and to attempt identify‐cation of factors associated with favorable response. Variables evaluated for a relationship to outcome included signalment, tumor location, presence of gross vs. microscopic tumor, radiation field size, irradiation technique, type of surgical procedure, completeness of excision, and chemotherapy (none, carboplatin alone, and others). Time to first event was calculated for the first day of treatment until local tumor recurrence or metastasis, or the date of euthanasia or death. Median time to first event for all 92 cats was 584 days. Only completeness of surgical excision was related to the time to first event. Median time to first event in cats having complete surgical excision was 986 days compared to 292 days for cats with incomplete excision (P = 0.004). Cats requiring bone removal to effect tumor removal had earlier failure than cats having other types of surgery. There was not a significant relationship between administration of chemotherapy or chemotherapy type and time to first event although outcome in cats receiving carboplatin was better than all other treatment groups. Carboplatin addition to preoperative irradiation appears worthy of further study. Pre‐operative irradiation is an effective treat‐ment for cats with vaccine associated sarcoma, especially if complete excision can be accomplished following irradiation.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Kobayashi, T and Hauck, ML and Dodge, R and Page, RL and Price, GS and Williams, LE and Hardie, EM and Mathews, KG and Thrall, DE}, year={2002}, pages={473–479} }
 @article{dickerson_page_ladue_hauck_thrall_stebbins_price_2001, title={Retrospective analysis of axial skeleton osteosarcoma in 22 large-breed dogs}, volume={15}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2001)015<0120:RAOASO>2.3.CO;2}, abstractNote={Medical-records of 22 large-breed dogs (>15 kg) with osteosarcoma (OSA) of the axial skeleton were reviewed to determine prevalence of metastasis and survival associated with this neoplasm. All dogs were treated with more than 1 mode of therapy including palliative radiation (n = 12), definitive radiation (n = 8), surgery (n = 7), chemotherapy (n = 12), or some combination of these therapies. Metastasis was documented in 10 of 22 dogs (46%), and the median survival for all dogs was 137 days. Primary cause of death was local tumor recurrence (54%). Breed (retriever versus purebred versus mixed-breed survival was 100, 182, and 264 days, respectively) and radiation therapy protocol (survival in dogs treated with palliative radiation therapy versus those treated with definitive radiation therapy was 79 and 265 days, respectively) were significantly related to survival (P < .05). Prevalence of metastasis and median survival for large-breed dogs with axial skeleton OSA seems to be similar to that reported for large-breed dogs with appendicular skeleton OSA. Definitive radiation therapy may have a role in the treatment of axial skeleton osteosarcoma.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Dickerson, ME and Page, RL and LaDue, TA and Hauck, ML and Thrall, DE and Stebbins, ME and Price, GS}, year={2001}, pages={120–124} }
 @article{savary_price_vaden_2000, title={Hypercalcemia in cats: A retrospective study of 71 cases (1991-1997)}, volume={14}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2000)014<0184:HICARS>2.3.CO;2}, abstractNote={A retrospective study was conducted to characterize the diseases, clinical findings, and clinicopathologic and ultrasonographic findings associated with hypercalcemia (serum calcium concentration >11 mg/dL) in 71 cats presented to North Carolina State University Veterinary Teaching Hospital. The 3 most common diagnoses were neoplasia (n = 21), renal failure (n = 18), and urolithiasis (n = 11). Primary hyperparathyroidism was diagnosed in 4 cats. Lymphoma and squamous cell carcinoma were the most frequently diagnosed tumors. Calcium oxalate uroliths were diagnosed in 8 of 11 cats with urolithiasis. Cats with neoplasia had a higher serum calcium concentration (13.5 +/- 2.5 mg/dL) than cats with renal failure or urolithiasis and renal failure (11.5 +/- 0.4 mg/dL; P < .03). Serum phosphorus concentration was higher in cats with renal failure than in cats with neoplasia (P < .004). Despite the fact that the majority of cats with uroliths were azotemic, their serum urea nitrogen and creatinine concentrations and urine specific gravity differed from that of cats with renal failure. Additional studies are warranted to determine the underlying disease mechanism in the cats we identified with hypercalcemia and urolithiasis. We also identified a small number of cats with diseases that are not commonly reported with hypercalcemia. Further studies are needed to determine whether an association exists between these diseases and hypercalcemia, as well as to characterize the underlying pathophysiologic mechanism for each disease process.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Savary, KCM and Price, GS and Vaden, SL}, year={2000}, pages={184–189} }
 @article{stell_price_swanson_2000, title={Implementation and assessment of a career and life skills program for matriculating veterinary medical students}, volume={217}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2000.217.1311}, number={9}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Stell, EJ and Price, GS and Swanson, C}, year={2000}, month={Nov}, pages={1311–1314} }
 @article{spugnini_thrall_price_sharp_munana_page_2000, title={Primary irradiation of canine intracranial masses}, volume={41}, ISSN={["1740-8261"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034220024&partnerID=MN8TOARS}, DOI={10.1111/j.1740-8261.2000.tb02091.x}, abstractNote={Twenty‐nine dogs received primary radiation therapy for intracranial lesions and clinical signs suggestive of neoplasia. Presumptive diagnosis and tumor categorization was based on computed toniographic or magnetic resonance images. Meningioma was the most likely tumor type in 22 dogs and glioma or choroid plexus tumors were tentatively identified in 4 and 3 dogs, respectively. Cobalt‐60 radiation was delivered in 3 Gy fractions on a daily, Monday‐through‐Friday basis for a total dose of 48 Gy (16 fractions) in 28 dogs; one dog received 54 Gy. Two of 29 dogs died during treatment of signs suggestive of progressive tumor growth but were included in the overall evaluation of response to treatment. Median overall survival was 250 days (range 21–804). Mild acute radiation effects on normal tissue developed and did not influence outcome in any dog. Late radiation effects could not be evaluated in this study. No significant predictive indicators were identified from the clinical or imaging data. Radiation therapy is superior to medical treatment of brain tumors in dogs with steroids, is useful for tumors that are not currently operable and may be preferable to surgical resection in dogs if the mass appears infiltrative. However, 22/29 (76%) dogs died of recurrent progressive neuropathy suggestive of tumor regrowth or progression. Thus, alternative methods for delivery of radiation to dogs with brain tumors or novel combinations of therapy should continue to undergo evaluation.}, number={4}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Spugnini, EP and Thrall, DE and Price, GS and Sharp, NJ and Munana, K and Page, RL}, year={2000}, pages={377–380} }
 @article{ladue_dodge_page_price_hauck_thrall_1999, title={Factors influencing survival after radiotherapy of nasal tumors in 130 dogs}, volume={40}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.1999.tb00367.x}, abstractNote={Improvements in survival of dogs with nasal tumors have been slow to develop throughout the past three decades. Despite multiple studies examining various radiation time‐dose schema, the advancement of CT‐based computerized treatment planning, and the evaluation of detailed staging systems, the optimal treatment regimen, and most important prognostic factors regarding survival remain unclear. In this study, data from four previous studies were combined with data from 44 additional dogs, and this population of 130 dogs was evaluated for factors which influenced survival. Twenty‐one dogs were treated with orthovoltage at the University of Pennsylvania. One hundred nine dogs were treated with cobalt photons at North Carolina State University. Sixty‐five of these 109 dogs had been previously described. Of the 44 dogs not previously described, 35 were treated with a shrinking field technique. Survival was determined from the medical record, or from information derived by telephone or mail survey. The univariate Cox regression model was used to examine for relationship between various patient, tumor, and treatment variables and survival. Significant relationships identified in the univariate analysis were further analyzed using the multivariate Cox regression model. Median survival of the 130 dogs was 8.9 months (95% C.I., 8–11 months). In the univariate analysis, the following variables were associated with decreased survival: 1) age >10 years old, 2) regional lymph node metastasis, 3) advanced tumor stage, 4) use of megavoltage radiation, 5) overall total dose >55 Gray, and 6) boost technique performed. In a multivariate analysis of 125 dogs with complete data for age, radiation type, and radiation dose, age (p< .001) and radiation type (p = .02) were identified as joint predictors of survival. After adjusting for age, the staging system lost prognostic significance (p = .06). In a subset of dogs that received cobalt radiation, after adjusting for age, dogs treated with a boost technique had decreased survival (p = .001). In general, local control of canine nasal tumors following aggressive radiation therapy is poor. Early diagnosis and selection of appropriate patients is warranted and palliative types of treatment should be considered in dogs with a poor chance of long term survival.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={LaDue, TA and Dodge, R and Page, RL and Price, GS and Hauck, ML and Thrall, DE}, year={1999}, pages={312–317} }
 @article{ramirez_dodge_page_price_hauck_ladue_nutter_thrall_1999, title={Palliative radiotherapy of appendicular osteosarcoma in 95 dogs}, volume={40}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.1999.tb00385.x}, abstractNote={Ninety‐five dogs with either a presumptive (n= 24) or biopsy confirmed diagnosis (n= 71) of soteosarcoma received palliative radiotherapy using60Co photons. Parallel opposed beams were used with each dog receivign either 10 Gy on days 0,7 and 21 (n= 58) or 8 Gy on days 0 and 7 (n= 37). The 8 Gy fractionation scheme was given with the intent of retreating upon relapse from pain relief. Only 9 of 37 (24%) dogs in the 8 Gy group returned for retreatment, Forty‐seven of the 95 dogs (49%) received concurrent or sequention chemotherapy. Seventy of the 95 dogs (74%) experienced pain relief following treatment. In dogs experiencing pain relief the median duration of response was 73 days. Numerous clinical variables were evaluated as predictors of response. The only variable significantly related to achieving a response was the use of chemotheraphy. The following variables were significanly related to the duration of response: extent of bone lysis, chemotherapy use, length of bone involved and tumor site (humerus). In a multivariate analysis (n= 73 dogs), after adjusting for chemotherapy use, extent of bone involvement (p= 0.01) and tumor site (p= 0.02) retained statistical significance, while degree of bone lysis did not (p= 0.11). No difference in response incidence or duration was found between 3 fractions of 10 Gy vs. 2 fractions of 8 Gy. Administration of a low initial dose with the intent of retreatment was not a successful strategy.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Ramirez, O and Dodge, RK and Page, RL and Price, GS and Hauck, ML and LaDue, TA and Nutter, F and Thrall, DE}, year={1999}, pages={517–522} }
 @article{mcgaughey_gould_gelernter_1998, title={Bt resistance management}, volume={16}, ISSN={["1087-0156"]}, DOI={10.1038/nbt0298-144}, number={2}, journal={NATURE BIOTECHNOLOGY}, author={McGaughey, WH and Gould, F and Gelernter, W}, year={1998}, month={Feb}, pages={144–146} }
 @article{hughes_vaden_manaugh_price_hudson_1998, title={Modulation of doxorubicin concentration by cyclosporin A in brain and testicular barrier tissues expressing P-glycoprotein in rats}, volume={37}, ISSN={["1573-7373"]}, DOI={10.1023/A:1005900908540}, abstractNote={P-glycoprotein (Pgp) is an inducible transmembrane protein that functions as an ATP-dependent efflux pump. Pgp is normally expressed in two types of cells: specialized epithelial cells with secretory/excretory functions (e.g., proximal renal tubules) and specialized endothelial cells (e.g., the capillary endothelial cells of the blood-brain barrier). In normal tissues, Pgp could exert a cytoprotective effect by facilitating excretion of drugs. It follows that inhibition of Pgp would alter the pharmacokinetics of drugs, like doxorubicin, in cells that express Pgp. The purpose of this study was to determine whether or not inhibition of Pgp by cyclosporin A (CsA) facilitated the transport of certain drugs across the blood tissue barriers of the brain and testes (barriers tissues expressing Pgp). 120 retired male breeder CD Fisher rats were randomly assigned to groups of 4 rats each. They were given either CsA, CsA vehicle, or saline followed by doxorubicin (Dox), cisplatin (CDDP), Evan's blue (EB), sodium fluorescein (NaF), or horseradish peroxidase (HRP). There was a CsA dose dependent increase in the tissue concentration of doxorubicin in brain and testes, but platinum (Pt) concentrations, derived from CDDP, were unaffected. Unlike CDDP, Dox, can be effluxed by Pgp. These increases in Dox concentrations were not due to altered vascular permeability as a result of CsA treatment as determined by lack of EB. NaF, or HRP in brain parenchyma. Modulation of Pgp function may prove to be useful for improving chemotherapy efficacy for patients with malignancies affecting tissues with blood-tissue barriers.}, number={1}, journal={JOURNAL OF NEURO-ONCOLOGY}, author={Hughes, CS and Vaden, SL and Manaugh, CA and Price, GS and Hudson, LC}, year={1998}, month={Mar}, pages={45–54} }
 @article{price_cline_page_riviere_thrall_1998, title={Potential complications associated with normothermic lonidamine infusion and with systemic acidosis in dogs receiving lonidamine during whole body hyperthermia (WBH)}, volume={14}, ISSN={["0265-6736"]}, DOI={10.3109/02656739809018232}, abstractNote={The vascular toxicosis of lonidamine (40 mg/h) or vehicle infusion was investigated in six dogs. Vasculitis and thrombosis were observed in veins infused with lonidamine but not in veins infused with vehicle. This finding suggests that it may not be possible to use lonidamine infusion to circumvent therapeutic limitations associated with the oral lonidamine formulation currently used in patients. We also investigated the systemic toxicosis of lonidamine (400 mg/m2; rapid intravenous bolus) or vehicle in six other dogs that developed systemic acidosis (pH < or = 7.0) during whole body hyperthermia (42 degrees C x 90 min). Gross and histologic haemorrhage was observed in all dogs; however, haemorrhagic lesions in acidotic dogs receiving lonidamine + WBH were more severe than changes observed in acidotic dogs receiving vehicle + WBH. These observations confirm the results of in vitro studies which suggest that the combined effect of lonidamine and hyperthermia is enhanced under acidic conditions. Furthermore, these findings indicate that acid-base status of patients receiving lonidamine during WBH must be monitored carefully to avoid serious complications.}, number={3}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Price, GS and Cline, JM and Page, RL and Riviere, JE and Thrall, DE}, year={1998}, pages={271–283} }
 @article{ladue_price_dodge_page_thrall_1998, title={Radiation therapy for incompletely resected canine mast cell tumors}, volume={39}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.1998.tb00326.x}, abstractNote={The records of 56 dogs treated with megavoltage radiation for mast cell neoplasia were reviewed to determine the efficacy of this treatment modality. Total radiation dose ranged from 45 to 57 Gray (Gy), dose per fraction ranged from 3.0 to 4.0 Gy, and radiation treatment time ranged from 14–28 days. Median disease free interval (95% CI) was 32.7 (19–70) months. Median disease free interval for dogs older than 7.5 years was 15 (lower limit 7) months as compared to 62 (lower limit 20) for dogs younger than 7.5 years of age (p = 0.006). Median disease free interval for dogs with measurable disease was 12 (lower limit 5) months as compared to 54 (32–70) months for dogs with microscopic disease (p = 0.006). Radiation treatment time was also significantly related to disease free interval. Median disease free interval for dogs treated longer than 22 days was 12 (7–19) months as compared to greater than 50 (lower limit 20) months for dogs treated in 22 or fewer days (p < 0.001). This appeared to be due to more recurrences in dogs treated with 3‐per‐week fractionation and suggests that tumor proliferation in the interfraction interval may be important. Sex, tumor location, histologic grade, WHO clinical stage, number of radiation fractions, total radiation dose, and dose‐per‐fraction, as well as the following “yes/no” variables: steroids given, surgery prior to radiation, lymph nodes irradiated, and development of another mast cell tumor did not appear to influence median disease free interval or survival. Data presented herein support megavoltage radiation as an effective treatment for canine mast cell neoplasia, and suggest that disease free interval in dogs treated with daily fractions may be longer than that achieved with alternating day fractions.}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={LaDue, T and Price, GS and Dodge, R and Page, RL and Thrall, DE}, year={1998}, pages={57–62} }
 @article{price_frazier_1998, title={Use of body surface area (BSA)-based dosages to calculate chemotherapeutic drug dose in dogs: I. Potential problems with current BSA formulae}, volume={12}, ISSN={["0891-6640"]}, DOI={10.1111/j.1939-1676.1998.tb02121.x}, abstractNote={The dose of most cancer chemotherapeutic drugs administered to dogs is calculated on the basis of estimated body surface area (BSA); however, results of some chemotherapy trials have revealed that this dosing method increases toxicosis in small dogs. The current formula used to estimate BSA in dogs may be inaccurate or the assumption that BSA correlates with chemotherapeutic drug exposure may be unfounded. Results presented in this review suggest that canine BSA estimates may be inaccurate because the values for the constant (K) and exponent (a) in the formulae (BSA = K.Wa) are incorrect or because a linear parameter such as body length is lacking from the formulae. Results that suggest the relationship between BSA and the physiologic/pharmacologic factors that influence drug exposure may not be closely correlated are also presented. Studies are warranted to determine whether there are dosing methods that normalize chemotherapeutic drug toxicity in dogs.}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Price, GS and Frazier, DL}, year={1998}, pages={267–271} }
 @article{frazier_price_1998, title={Use of body surface area to calculate chemotherapeutic drug dose in dogs: II. Limitations imposed by pharmacokinetic factors}, volume={12}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.1998.tb02122.x}, abstractNote={Anticancer drug dosages that specify the maximum dose and minimum dosing interval that are tolerated in a population of dogs are commonly recommended. Because the differences between the effective and toxic doses of most cancer chemotherapeutics is slight, it is important to achieve therapeutic concentrations in tumor tissues at the same time that concentrations in nontarget tissues are minimized. In order to determine the dosage regimen that will most likely accomplish these goals, similar drug concentrations must be achieved in all patients dosed according to a specific regimen. Dosing based on body surface area (BSA) is generally used in an effort to normalize drug concentrations. This is because it is well recognized that measures of many physiologic parameters that are responsible for drug disposition, including renal function and energy expenditure, can be normalized by use of BSA. However, there is substantial evidence that drug disposition is not always proportional to BSA. Differences in distribution, metabolism, and excretion pathways may preclude dose extrapolation among species or among individuals within a species based on BSA. Moreover, genetic differences in drug metabolism are well recognized in humans and in laboratory animals, and it is likely that similar differences exist among breeds of dogs. A review of the pharmacokinetic disposition of several cancer chemotherapeutics suggests that studies are needed to determine the most effective method to achieve equivalent anticancer drug concentrations in diverse veterinary patients.}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Frazier, DL and Price, GS}, year={1998}, pages={272–278} }
 @article{price_page_riviere_cline_thrall_1996, title={Pharmacokinetics and toxicity of oral and intravenous lonidamine in dogs}, volume={38}, ISSN={["0344-5704"]}, DOI={10.1007/s002800050460}, abstractNote={Plasma lonidamine concentration and toxicity were investigated in dogs receiving 100, 200, 400, 800, 1200 mg/m2 orally twice daily for 30 days and in dogs receiving single intravenous doses of 200, 400, 800, 1200 mg/m2. Physical or laboratory signs of toxicity were not observed in dogs receiving oral lonidamine, but severe vomiting and signs of acute hepatic and pancreatic toxicity were observed in dogs receiving intravenous doses that exceeded 400 mg/m2. The area under the lonidamine concentration versus time curve (AUC) in dogs receiving 200, 400, and 800 mg/m2 of lonidamine intravenously was a 1.8-, 3.3-, and 8.7-fold higher than in dogs receiving oral lonidamine. This suggests that the bioavailability of oral lonidamine may be limited. However, centrilobular hepatocellular swelling and vacuolation were observed in dogs receiving oral lonidamine. Serum alanine aminotransferase (ALT) activity was increased in dogs receiving intra-venous lonidamine. These findings suggest that lonidamine is hepatotoxic in dogs. However, serum ALT was increased in only 1/4 dogs receiving 400 mg/m2 of lonidamine intravenously and plasma concentration were within the range capable of sensitizing hyperthermia and chemotherapy. Therefore, this dose and route appears to be a viable and controllable method for prospective quantification of lonidamine interaction with systemic chemotherapy and/or hyperthermia.}, number={2}, journal={CANCER CHEMOTHERAPY AND PHARMACOLOGY}, author={Price, GS and Page, RL and Riviere, JE and Cline, JM and Thrall, DE}, year={1996}, month={Jun}, pages={129–135} }
 @article{hauck_price_ogilvie_johnson_gillette_thrall_dewhirst_page_1996, title={Phase I evaluation of mitoxantrone alone and combined with whole body hyperthermia in dogs with lymphoma}, volume={12}, ISSN={["0265-6736"]}, DOI={10.3109/02656739609022520}, abstractNote={The maximum tolerated dose of mitoxantrone (MX) administered alone or combined with whole body hyperthermia (WBH) was determined in this nonrandomized, prospective study in dogs with lymphoma. MX was administered to 53 dogs every three weeks for a total of six treatments unless progressive disease or persistent, severe toxicity developed. Fifty dogs were evaluable (MX alone n = 30, MX/WBH n = 20). MX was administered as a 1 h infusion at the onset of the plateau phase of WBH in dogs treated with combined therapy. Dogs were evaluated weekly between treatments for the first four treatments with physical examination and complete blood counts to define acute and cumulative toxicity. Dogs were evaluated every three weeks for tumour response until relapse. The maximum tolerated dose (MTD) was defined as that dose in each group that resulted in a 50% incidence of moderate or severe toxicity as estimated from logistic regression analysis of the toxicity data. Myelosuppression was the only toxicity observed. Neutropenia was equal in frequency and severity between treatment groups. Thrombocytopenia was not observed in any dog receiving MX/WBH but occurred in 13% of dogs treated with MX alone. The MTD for MX +/- WBH was 6.1 +/- 0.6 and 6.5 +/- 0.8mg/M2 respectively. A steeper dose response relationship was observed in dogs receiving combined therapy compared to dogs treated with MX alone suggesting WBH may improve the uniformity of patient response to chemotherapy. We concluded that MX may be administered without dose reduction to dogs undergoing WBH and that MX should be evaluated more thoroughly in future thermochemotherapy studies.}, number={3}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Hauck, ML and Price, GS and Ogilvie, GK and Johnson, J and Gillette, EL and Thrall, DE and Dewhirst, MW and Page, RL}, year={1996}, pages={309–320} }
 @article{price_page_riviere_cline_frazier_thrall_1995, title={EFFECT OF WHOLE-BODY HYPERTHERMIA ON LONIDAMINE AND DOXORUBICIN PHARMACOKINETICS AND TOXICITY IN DOGS}, volume={11}, ISSN={["0265-6736"]}, DOI={10.3109/02656739509022489}, abstractNote={Six cycles of the maximum tolerable intravenous doses of lonidamine (400 mg/m2) and doxorubicin (30 mg/m2) were administered to three normothermic dogs and three dogs undergoing whole-body hyperthermia (WBH) (42 degrees C X 90 min), at 3-week intervals. Lonidamine pharmacokinetics was unaltered by WBH. WBH increased doxorubicin clearance 1.6-fold, however this trend was not statistically significant. WBH resulted in a 2.4-fold increase in the volume of distribution (Vdss) of doxorubicin relative to dogs treated under euthermic conditions (p < 0.001). This finding suggests tissue extraction of doxorubicin was increased by WBH. The specific tissues in which this occurred is unknown, but myelosuppression and cardiotoxicity were only minimally increased. Therefore, doxorubicin uptake in critical normal tissues was probably unaffected. The biochemical and haematologic toxicities observed 6 h and 1 week after each treatment did not appear to differ in character or severity from that reported in dogs receiving lonidamine +/- WBH or doxorubicin +/- WBH. These results suggest WBH did not decrease the maximum tolerable dose of doxorubicin when given with lonidamine, and that the antitumour activity of this combination should be assessed.}, number={4}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={PRICE, GS and PAGE, RL and RIVIERE, JE and CLINE, JM and FRAZIER, DL and THRALL, DE}, year={1995}, pages={545–559} }
 @article{price_page_riviere_cline_thrall_1995, title={EFFECT OF WHOLE-BODY HYPERTHERMIA ON THE PHARMACOKINETICS AND TOXICITY OF LONIDAMINE IN DOGS}, volume={11}, ISSN={["0265-6736"]}, DOI={10.3109/02656739509022488}, abstractNote={The pharmacokinetics and toxicity of intravenous lonidamine were investigated in dogs receiving four cycles of lonidamine (400 or 800 mg/m2) +/- whole-body hyperthermia (WBH). Clearance and volume of distribution in dogs receiving lonidamine during WBH increased 1.6-2.3 and 1.9-3.5-fold respectively, relative to dogs receiving lonidamine under euthermic conditions (p < 0.02). In dogs receiving lonidamine under euthermic conditions or 400 mg/m2 + WBH, the area under the lonidamine concentration versus time curve (AUC) measured during the fourth treatment was 21-58% lower than the first treatment AUC. However, in dogs receiving 800 mg/m2 + WBH, the fourth treatment AUC was four-fold higher than the first treatment AUC (p < 0.02). This suggests repeated exposure to 800 mg/m2 lonidamine and WBH impairs lonidamine metabolism. Weakness, hypoglycaemia, and elevations in amylase, alanine aminotransferase, alkaline phosphatase and bilirubin were more severe or occurred exclusively in dogs receiving 800 mg/m2 + WBH. Since these changes were attributable to marked AUC increases, which occurred secondary to repeated exposure to 800 mg/m2 lonidamine during WBH, 400 mg/m2 was identified as the maximum tolerable dose to be administered intravenously to dogs during WBH.}, number={4}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={PRICE, GS and PAGE, RL and RIVIERE, JE and CLINE, JM and THRALL, DE}, year={1995}, pages={531–544} }
 @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{page_thrall_george_price_heidner_mcentee_novotney_hauck_dewhirst_1992, title={QUANTITATIVE ESTIMATION OF THE THERMAL DOSE-MODIFYING FACTOR FOR CIS-DIAMMINEDICHLOROPLATINUM (CDDP) IN TUMOR-BEARING DOGS}, volume={8}, ISSN={["0265-6736"]}, DOI={10.3109/02656739209005024}, abstractNote={A statistical method for estimating clinical toxicity was used to determine a theoretical isoeffect dose-modifying factor for dogs with disseminated or refractory neoplasia treated with cis-diammine dichloroplatinum (II) plus whole-body hyperthermia or CDDP alone. CDDP was administered every 3 weeks with vigorous saline hydration to 54 dogs (CDDP alone n = 21, CDDP/WBH n = 33) that were eligible for entry into this non-randomized study. CDDP was administered during the plateau phase of WBH in dogs receiving combined therapy. Acute toxicity included myelosuppression (CDDP n = 7; CDDP/WBH n = 5), nephrotoxicity (CDDP n = 1, CDDP/WBH n = 1) and respiratory distress (CDDP/WBH n = 2). Eight dogs experienced chronic renal dysfunction as a result of CDDP (n = 2) or CDDP/WBH (n = 6). A theoretical thermal dose-modifying factor was determined for both acute and cumulative toxicity by comparing the maximum tolerated dose of each treatment group. The maximum tolerated dose (MTD) of CDDP +/- WBH was defined as that dose producing a 50% incidence of moderate acute toxicity or acute plus mild chronic toxicity as estimated from logistic regression analysis of the toxicity data. The MTD (+/- .standard error) of CDDP/WBH for acute toxicity only was 54.6 (4.3) mg/M2 and for CDDP alone the MTD was 73.6 (40) mg/M2. Thus, the isoeffect dose-modifying factor for acute toxicity was 1.35 (0.12). The MTD (SE) of CDDP/WBH for cumulative toxicity (acute plus chronic toxicity) was 46.4 (2.7) mg/M2 and for CDDP alone waas 70.0 (2.9) mg/M2. The isoeffect dose-modifying factor for total cumulative toxicity was 1.5 (0.1).(ABSTRACT TRUNCATED AT 250 WORDS)}, number={6}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={PAGE, RL and THRALL, DE and GEORGE, SL and PRICE, GS and HEIDNER, GL and MCENTEE, MC and NOVOTNEY, CA and HAUCK, ML and DEWHIRST, MW}, year={1992}, pages={761–769} }