@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{poulson_dewhirst_gaskin_vujaskovic_samulski_prescott_meyer_page_thrall_2000, title={Acute pancreatitis associated with administration of a nitric oxide synthase inhibitor in tumor-bearing dogs}, volume={14}, number={6}, journal={In Vivo (Athens, Greece)}, author={Poulson, J. M. and Dewhirst, M. W. and Gaskin, A. A. and Vujaskovic, Z. and Samulski, T. V. and Prescott, D. M. and Meyer, R. E. and Page, R. L. and Thrall, D. E.}, year={2000}, pages={709–714} }
 @article{page_hughes_huyan_sagris_trogdon_2000, title={Modulation of P-glycoprotein-mediated doxorubicin resistance in canine cell lines}, volume={20}, number={5B}, journal={Anticancer Research}, author={Page, R. L. and Hughes, C. S. and Huyan, S. and Sagris, J. and Trogdon, M.}, year={2000}, pages={3533–3538} }
 @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{mcentee_page_mauldin_thrall_2000, title={Results of irradiation of infiltrative lipoma in 13 dogs}, volume={41}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2000.tb01889.x}, abstractNote={Thirteen dogs with infiltrative lipomas were treated with cobalt 60 radiation. Four of the thirteen dogs also received either whole body (n = 2) or combination local/whole body (n = 2) hyperthermia in conjunction with radiation therapy. Cytoreductive surgery was performed prior to radiation in 10 dogs, although only 3 dogs had microscopic disease at the time of radiation therapy. Dogs received a total dose of 45.6 Gy–63 Gy in 2.5–4 Gy/fraction on either a Monday/Wednesday/Friday schedule or on a daily Monday through Friday schedule. Twelve of the 13 dogs had computed tomography (CT) images acquired prior to irradiation. Survival time was determined from the time of completion of radiation therapy. Survival ranged from 6 months to 94 months, with a median (95% confidence interval) of 40 (18.5–77) months and a mean of 46.4 months. Only one dog was euthanized due to persistent signs related to the infiltrative lipoma at 6 months after the end of radiation therapy. There was no apparent difference in response based on whether or not the dogs received hyperthermia in conjunction with irradiation, although the numbers were too small to make any significant conclusions. It appears that dogs with infiltrative lipomas can benefit from external beam irradiation alone or in combination with surgery to effect long‐term local tumor control.}, number={6}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={McEntee, MC and Page, RL and Mauldin, GN and Thrall, DE}, year={2000}, pages={554–556} }
 @article{vujaskovic_poulson_gaskin_thrall_page_charles_macfall_brizel_meyer_prescott_et al._2000, title={Temperature-dependent changes in physiologic parameters of spontaneous canine soft tissue sarcomas after combined radiotherapy and hyperthermia treatment}, volume={46}, ISSN={["0360-3016"]}, DOI={10.1016/s0360-3016(99)00362-4}, abstractNote={The objectives of this study were to evaluate effects of hyperthermia on tumor oxygenation, extracellular pH (pHe), and blood flow in 13 dogs with spontaneous soft tissue sarcomas prior to and after local hyperthermia.Tumor pO2 was measured using an Eppendorf polarographic device, pHe using interstitial electrodes, and blood flow using contrast-enhanced magnetic resonance imaging (MRI).There was an overall improvement in tumor oxygenation observed as an increase in median pO2 and decrease in hypoxic fraction (% of pO2 measurements <5 mm Hg) at 24-h post hyperthermia. These changes were most pronounced when the median temperature (T50) during hyperthermia treatment was less than 44 degrees C. Tumors with T50 > 44 degrees C were characterized by a decrease in median PO2 and an increase in hypoxic fraction. Similar thermal dose-related changes were observed in tumor perfusion. Perfusion was significantly higher after hyperthermia. Increases in perfusion were most evident in tumors with T50 < 44 degrees C. With T50 > 44 degrees C, there was no change in perfusion after hyperthermia. On average, pHe values declined in all animals after hyperthermia, with the greatest reduction seen for larger T50 values.This study suggests that hyperthermia has biphasic effects on tumor physiologic parameters. Lower temperatures tend to favor improved perfusion and oxygenation, whereas higher temperatures are more likely to cause vascular damage, thus leading to greater hypoxia. While it has long been recognized that such effects occur in rodent tumors, this is the first report to tie such changes to temperatures achieved during hyperthermia in the clinical setting. Furthermore, it suggests that the thermal threshold for vascular damage is higher in spontaneous tumors than in more rapidly growing rodent tumors.}, number={1}, journal={INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS}, author={Vujaskovic, Z and Poulson, JM and Gaskin, AA and Thrall, DE and Page, RL and Charles, HC and MacFall, JR and Brizel, DM and Meyer, RE and Prescott, DM and et al.}, year={2000}, month={Jan}, pages={179–185} }
 @article{case_hauck_yeager_simkins_serres_schmith_dillberger_page_2000, title={The pharmacokinetics and pharmacodynamics of GW395058, a peptide agonist of the thrombopoietin receptor, in the dog, a large-animal model of chemotherapy-induced thrombocytopenia}, volume={18}, ISSN={["1066-5099"]}, DOI={10.1634/stemcells.18-5-360}, abstractNote={GW395058, a PEGylated peptide agonist of the thrombopoietin receptor, stimulates megakaryocytopoiesis and has previously been shown to increase platelet counts in vivo. The pharmacokinetics and pharmacodynamics of GW395058 were characterized using a randomized, crossover study in a large‐animal model (dog) of chemotherapy‐induced thrombocytopenia.}, number={5}, journal={STEM CELLS}, author={Case, BC and Hauck, ML and Yeager, RL and Simkins, AH and Serres, M and Schmith, VD and Dillberger, JE and Page, RL}, year={2000}, pages={360–365} }
 @article{prescott_charles_poulson_page_thrall_vujaskovic_dewhirst_2000, title={The relationship between intracellular and extracellular pH in spontaneous canine tumors}, volume={6}, number={6}, journal={Clinical Cancer Research}, author={Prescott, D. M. and Charles, H. C. and Poulson, J. M. and Page, R. L. and Thrall, D. E. and Vujaskovic, Z. and Dewhirst, M. W.}, year={2000}, pages={2501–2505} }
 @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{waddle_fine_case_trogdon_tyczkowska_frazier_page_1999, title={Phase I and pharmacokinetic analysis of high-dose tamoxifen and chemotherapy in normal and tumor-bearing dogs}, volume={44}, ISSN={["0344-5704"]}, DOI={10.1007/s002800050947}, abstractNote={{"Label"=>"PURPOSE", "NlmCategory"=>"OBJECTIVE"} To determine whether tamoxifen plasma concentrations capable of blocking P-glycoprotein (Pgp) in vitro can be safely achieved in dogs and whether doxorubicin pharmacokinetic alterations occur when tamoxifen is coadministered. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} Tamoxifen dose escalation studies were conducted in 7 normal dogs and in 19 tumor-bearing dogs receiving full-dose chemotherapy. Plasma tamoxifen and serum doxorubicin disposition were analyzed for putative drug interactions. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} Steady-state plasma concentrations of tamoxifen and N-desmethyl tamoxifen (NDMT) were 5-10 microM following oral tamoxifen administration at 600 mg/m2 every 12 h for 7 days to normal and tumor-bearing dogs. Mild-moderate gastrointestinal toxicity (diarrhea, anorexia) and reversible neurotoxicity were observed in dogs receiving chemotherapy plus high-dose tamoxifen. Myelosuppression was not affected by combined treatment in tumor-bearing dogs. High-dose tamoxifen decreased the clearance and volume of distribution of full-dose doxorubicin. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} Concentrations of tamoxifen/ NDMT sufficient to inhibit Pgp may be achieved in dogs receiving full-dose chemotherapy with a moderate but acceptable increase in gastrointestinal toxicity. Tamoxifen affects doxorubicin metabolism in dogs at high doses resulting in increased serum exposure. Pharmacologic manipulation of Pgp expression or function in normal and tumor tissue in dogs may facilitate investigation of novel anticancer treatment strategies in humans.}, number={1}, journal={CANCER CHEMOTHERAPY AND PHARMACOLOGY}, author={Waddle, JR and Fine, RL and Case, BC and Trogdon, ML and Tyczkowska, K and Frazier, D and Page, RL}, year={1999}, month={Jul}, pages={74–80} }
 @article{larue_fox_ogilvie_page_getzy_thrall_johnson_dewhirst_gillette_1999, title={Tumour cell kinetics as predictors of response in canine lymphoma treated with chemotherapy alone or combined with whole body hyperthermia}, volume={15}, DOI={10.1080/026567399285477}, abstractNote={Kinetic parameters including potential doubling time (Tpot), duration of S phase (Ts), labelling index (LI), and DNA index (DI) were obtained from 42 dogs with previously untreated lymphoma. Standard flow cytometric techniques using BrdUrd were employed. All dogs were treated with L-asparaginase and remission was induced in 26 dogs, which were then randomized to receive chemotherapy only (doxorubicin [DOX] alone or with lonidamine) or chemotherapy plus whole body hyperthermia (WBH). Dogs were treated every 3 weeks for up to five treatments and evaluated every 3 weeks for evidence of tumour recurrence. Within this subset of animals there was no difference in outcome based on treatment group. Median values for Tpot, Ts and LI were 3.4 days, 7.23 h and 12.49%, respectively. Dogs that had tumours with LI > or = 20% had a shorter time until recurrence than dogs with tumours characterized by LI < 20%. In dogs treated only with chemotherapy, dogs bearing tumours with longer than median Tpot and Ts values and lower than median LI had significantly longer remission duration than dogs with more rapidly proliferating tumours. Dogs treated only with chemotherapy, which had longer than median Tpot and Ts values and lower than median LI, had significantly longer remission duration than all other dogs in the study. The mechanisms in which kinetics are associated with response to chemotherapy are not clear and vary depending on tumour type and treatment regimen. More work is needed to understand factors involved in cell killing during in vivo hyperthermia.}, number={6}, journal={International Journal of Hyperthermia}, author={Larue, S. M. and Fox, M. H. and Ogilvie, G. K. and Page, R. L. and Getzy, D. M. and Thrall, D. E. and Johnson, J. L. and Dewhirst, M. W. and Gillette, E. L.}, year={1999}, pages={475–486} }
 @article{thrall_larue_powers_page_johnson_george_kornegay_mcentee_levesque_smith_et al._1999, title={Use of whole body hyperthermia as a method to heat inaccessible tumours uniformly: a phase III trial in canine brain masses}, volume={15}, number={5}, journal={International Journal of Hyperthermia}, author={Thrall, D. E. and Larue, S. M. and Powers, B. E. and Page, R. L. and Johnson, J. and George, S. L. and Kornegay, J. N. and McEntee, M. C. and Levesque, D. C. and Smith, M. and et al.}, year={1999}, pages={383–398} }
 @article{rusbridge_wheeler_lamb_page_carmichael_brearley_bjornson_1999, title={Vertebral plasma cell tumors in 8 dogs}, volume={13}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(1999)013<0126:VPCTID>2.3.CO;2}, abstractNote={The case histories of 8 dogs with spinal pain and neurologic deficits associated with vertebral plasma cell tumor are reviewed. Four dogs had solitary plasmacytoma, 3 had multiple myeloma, and 1 dog had 2 vertebral lesions with no evidence of disseminated disease. Four dogs were treated: 2 with multiple myeloma received chemotherapy only and survived 17 and 26 months, respectively. Two dogs with solitary plasmacytomas of the spine had chemotherapy and radiotherapy: the 1st survived 4 months and was euthanized after developing radiation myelopathy; the 2nd survived 65 months before developing multiple myeloma. The diagnosis of solitary plasmacytoma of the spine versus multiple myeloma is discussed.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Rusbridge, C and Wheeler, SJ and Lamb, CR and Page, RL and Carmichael, S and Brearley, MJ and Bjornson, AP}, year={1999}, pages={126–133} }
 @article{applewhite_page_ramirez_1999, title={What is your diagnosis? Radiographic Diagnosis - Substantial soft tissue swelling on the dorsal and palmar surfaces of the carpus?}, volume={214}, number={1}, journal={Journal of the American Veterinary Medical Association}, author={Applewhite, A. A. and Page, R. L. and Ramirez, O.}, year={1999}, pages={29–30} }
 @article{applewhite_page_ramirez_1999, title={What is your diagnosis? Soft tissue neoplasm of the right carpus in a dog}, volume={214}, number={1}, journal={Journal of the American Veterinary Medical Association}, author={Applewhite, A. A. and Page, R. L. and Ramirez, O., III}, year={1999}, pages={29–30} }
 @article{steingold_sharp_mcgahan_hughes_dunn_page_1998, title={Characterization of canine MDR1 mRNA: Its abundance in drug resistant cell lines and in vivo}, volume={18}, number={1A}, journal={Anticancer Research}, author={Steingold, S. F. and Sharp, N. J. and McGahan, M. C. and Hughes, C. S. and Dunn, S. E. and Page, R. L.}, year={1998}, pages={393–400} }
 @article{grindem_page_ammerman_breitschwerdt_1998, title={Immunophenotypic Comparison of Blood and Lymph Node from Dogs with Lymphoma}, volume={27}, ISSN={0275-6382 1939-165X}, url={http://dx.doi.org/10.1111/j.1939-165X.1998.tb01075.x}, DOI={10.1111/j.1939-165X.1998.tb01075.x}, abstractNote={Abstract— Peripheral blood and lymph node tissue from 12 dogs with lymphoma was immunophenotyped. Additionally, the bone marrow was immunophenotyped in 6 dogs. The lymphomas were characterized as B‐cell in 11 dogs and T‐cell in 1 dog. Immunophenotypic patterns in the peripheral blood and bone marrow were variable. The trend in dogs with B‐cell lymphoma was normal to increased percentage of IgG‐positive cells, decreased percentage of pan‐T‐positive cells, decreased percentage of CD4‐positive cells, and decreased CD4/CD8 ratio. Simultaneous immunophenotyping of lymph node, blood and bone marrow cannot be recommended routinely without further studies to document its value as an independent prognostic indicator. However, it is potentially useful for tumor staging and monitoring remission, especially in lymphoma patients with a leukemic phase.}, number={1}, journal={Veterinary Clinical Pathology}, publisher={Wiley}, author={Grindem, Carol B. and Page, Rodney L. and Ammerman, B.E. and Breitschwerdt, Edward B.}, year={1998}, month={Mar}, pages={16–20} }
 @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{cronin_page_spodnick_dodge_hardie_price_ruslander_thrall_1998, title={Radiation therapy and surgery for fibrosarcoma in 33 cats}, volume={39}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.1998.tb00325.x}, abstractNote={Thirty‐three cats with histologically confirmed fibrosarcomas were treated with radiation therapy followed by surgery. The median (95% confidence interval) disease free interval and overall survival were 398 (261,924) and 600 (lower limit 515) days, respectively. There were 19 treatment failures; 11 cats had only local recurrence, 4 cats developed metastatic disease, 3 cats had local recurrence followed by metastasis, and 1 cat developed simultaneous local and distant disease. Twelve cats are alive and discase free. Two cats died without evidence of treatment failure. The presence of tumor cells at the margin of resected tissue after radiation was the only variable which influenced treatment success. The median (95% confidence interval) disease free interval in 5 cats with tumor cells at the margin of the resected specimen was 112 (94,150) days versus 700 (lower limit 328) days for 26 cats with negative tumor margins, p<0.0001. We did not identify a relationship between tumor volume, number of prior tumor excisions, concomitant use of chemotherapy or various descriptors of the radiation therapy technique and disease free interval.}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Cronin, K and Page, RL and Spodnick, G and Dodge, R and Hardie, EN and Price, GS and Ruslander, D and Thrall, DE}, year={1998}, pages={51–56} }
 @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{starrak_berry_page_johnson_thrall_1997, title={Correlation between thoracic radiographic changes and remission/survival duration in 270 dogs with lymphosarcoma}, volume={38}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.1997.tb00863.x}, abstractNote={A retrospective study was undertaken wherein the medical records and thoracic radiographs of 270 dogs with lymphosarcoma were reviewed to determine the type and frequency of thoracic radiographic changes. Statistical evaluation of the relationship between radiographic, clinical and immunologic factors and the primary remission duration and survival times was performed using univariate and multivariate analysis. One hundred ninety‐two dogs (71 %) had some type of thoracic radiographicabnormality, including 80 dogs (29.6%) with pulmonary infiltrates and 164 dogs (64.4%) with thoracic lymphadenomegaly. Only T‐cell phenotype (p = 0.0056 for survival, p = 0.0045 for remission) and the presence of cranial mediastinal lymphadenomegaly (p = 0.0005 for survival, p = 0.0129 for remission) were identified as having a significant negative correlation to both primary remission and survival duration by multivariate analysis.}, number={6}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Starrak, GS and Berry, CR and Page, RL and Johnson, JL and Thrall, DE}, year={1997}, pages={411–418} }
 @article{ruslander_gebhard_tompkins_grindem_page_1997, title={Immunophenotypic characterization of canine lymphoproliferative disorders}, volume={11}, number={2}, journal={In Vivo (Athens, Greece)}, author={Ruslander, D. A. and Gebhard, D. H. and Tompkins, M. B. and Grindem, C. B. and Page, R. L.}, year={1997}, pages={169–172} }
 @article{vaden_page_riviere_1996, title={An in vitro-in vivo validation of the isolated perfused tumor and skin flap preparation as a model of cisplatin delivery to tumors}, volume={35}, ISSN={["1056-8719"]}, DOI={10.1016/1056-8719(96)00044-5}, abstractNote={The isolated perfused tumor and skin flap (IPTSF) is a unique model system in which drug disposition is evaluated in tumor tissue and surrounding normal tissue, both of which are supplied by the same vascular system. We compared tissue Pt concentrations obtained following systemic administration of cisplatin (CDDP) to whole pigs bearing tumored skin flaps with data obtained from IPTSF treated similarly. During the in vivo study, CDDP was administered intravenously to six pigs that had tumor and skin flaps. IPTSF were created in four pigs and isolated in a perfusion chamber and perfused with medium containing CDDP for 180 min. Venous plasma or perfusate samples were serially collected throughout perfusion. Tissue samples were collected after perfusion was complete. All samples were assayed for Pt by atomic absorption spectroscopy. Area under the curve of Pt profiles from IPTSF and in vivo perfused flaps were not significantly different. Pt concentrations were significantly higher in tumor samples from in vivo perfused flaps than in samples from IPTSF. Pt concentrations in skin and subcutaneous tissue were not significantly different. When consideration is given to all of the potential variables that were operative in these experiments, the results of this study demonstrate that Pt distribution within the IPTSF was comparable to that obtained in vivo.}, number={3}, journal={JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS}, author={Vaden, SL and Page, RL and Riviere, JE}, year={1996}, month={Jun}, pages={173–177} }
 @article{page_lee_riviere_dodge_thrall_dewhirst_1996, title={Cisplatin-derived Pt [platinum] distribution in canine normal and tumor tissue}, volume={20}, number={3}, journal={Veterinary Cancer Society Newsletter}, author={Page, R. L. and Lee, J. and Riviere, J. E. and Dodge, R. K. and Thrall, D. E. and Dewhirst, M. W.}, year={1996}, pages={1} }
 @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{page_lee_riviere_dodge_thrall_dewhirst_1995, title={Absence of whole body hyperthermia effect on cisplatin distribution in spontaneous canine tumors}, volume={32}, ISSN={0360-3016}, url={http://dx.doi.org/10.1016/0360-3016(94)00483-2}, DOI={10.1016/0360-3016(94)00483-2}, abstractNote={This study was conducted to evaluate the effect of whole body hyperthermia (WBH) on cisplatin (CDDP)-derived platinum (Pt) disposition in tumor and normal tissue in dogs with spontaneously arising neoplasia undergoing conventional pretreatment diuresis.Cisplatin was administered to 12 dogs with terminal stage, metastatic neoplasia. Cisplatin (50 mg/M2 over 1 h) was administered following 4 h of forced fluid diuresis (0.9% saline at 10 ml/kg/h). Six of the 12 dogs underwent a WBH procedure (42 degrees C rectal temperature x 90 min) simultaneously with CDDP infusion. Dogs were euthanized following the CDDP infusion, and samples from critical organs, tumor, and normal tissue adjacent to the tumor were immediately collected.No significant differences existed between groups in serum or normal tissue Pt content. Thirty-eight tumor samples were obtained from 27 tumors in the six dogs included in the normothermic group and 43 tumor samples were obtained from 29 tumors in the six dogs undergoing WBH. Tumor volume varied from 0.08 cm3 to 2270 cm3 and multiple samples were obtained from tumors greater than 3 cm in diameter. Twenty-five paired tissue samples of tumor and adjacent normal tissue were collected from dogs in the normothermic group and 31 paired samples were obtained from the hyperthermic group. No differences were observed between groups in tumor Pt content or in the tumor/normal tissue Pt ratios.Pt disposition was unaffected by WBH under conditions reported in this study. A forced diuresis is necessary to clinically administer CDDP at maximally tolerable doses. This maneuver results in increased blood flow to critical normal tissue that seemingly obviates any hyperthermia-induced alterations in drug disposition.}, number={4}, journal={International Journal of Radiation Oncology*Biology*Physics}, publisher={Elsevier BV}, author={Page, R.L. and Lee, J. and Riviere, J.E. and Dodge, R.K. and Thrall, D.E. and Dewhirst, M.W.}, year={1995}, month={Jul}, pages={1097–1102} }
 @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{vaden_page_williams_riviere_1994, title={EFFECT OF HYPERTHERMIA ON CISPLATIN AND CARBOPLATIN DISPOSITION IN THE ISOLATED, PERFUSED TUMOR AND SKIN FLAP}, volume={10}, ISSN={["0265-6736"]}, DOI={10.3109/02656739409009358}, abstractNote={The effect of hyperthermia on the disposition of platinum (Pt) from cisplatin (CDDP) and carboplatin (CBDCA) in the isolated, perfused tumour and skin flap (IPTSF) was evaluated. Flaps (n = 4/treatment) were perfused with 3.0 micrograms CDDP or 15 micrograms CBDCA/ml perfusion medium at a rate of 1 ml/min for 3 h. Two-hour (CDDP experiments) or 3 h (CBDCA experiments) washout phases were then performed. The disposition kinetics of free Pt were characterized using a four-compartment, physiologically relevant, pharmacokinetic model. Hyperthermia (HT) may have enhanced the mobility of Pt but it did not increase total Pt mass in the tissue compartments in CDDP experiments. Conversely, HT significantly increased Pt mass in the fixed, non-tumour tissue compartment (p < 0.05) in CBDCA experiments. While a similar trend was noted in the fixed, tumour tissue compartment of CBDCA-treated flaps, the difference was not significant (p = 0.17). Total tissue Pt mass was significantly greater in CDDP compared with CBDCA experiments (p < 0.05). In conclusion, HT alters the disposition of Pt from CDDP and CBDCA under conditions of constant rate infusion. Further characterization of factors influencing drug disposition to non-tumour and tumour tissues can be systematically accomplished using the IPTSF.}, number={4}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={VADEN, SL and PAGE, RL and WILLIAMS, PL and RIVIERE, JE}, year={1994}, pages={563–572} }
 @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_garg_vaidyanathan_zalutsky_1994, title={PRECLINICAL EVALUATION AND PET IMAGING OF F-18 LABELED MEL-14 F(AB')(2) FRAGMENT IN NORMAL DOGS}, volume={21}, ISSN={["1872-9614"]}, DOI={10.1016/0969-8051(94)90079-5}, abstractNote={The F(ab')2 fragment of monoclonal antibody Mel-14, reactive with human melanomas and gliomas, was labeled with 18F using two acylation agents, N-succinimidyl 8-[(4'-[18F]fluorobenzyl)amino]suberate (SFBS) and N-succinimidyl 4-[18F]fluorobenzoate (SFB). The immunoreactivity and affinity for Mel-14 F(ab')2 labeled using the two methods were similar. As a prelude to human clinical evaluation, PET imaging, tissue distribution and pharmacokinetic measurements were performed in two groups of normal foxhounds. Similar in vivo behavior was seen for Mel-14 F(ab')2 labeled using SFBS and SFB. Radiation dosimetry calculations suggest that a 10 mCi dose could be used for this F(ab')2 fragment labeled using either acylation agent.}, number={7}, journal={NUCLEAR MEDICINE AND BIOLOGY}, author={PAGE, RL and GARG, PK and VAIDYANATHAN, G and ZALUTSKY, MR}, year={1994}, month={Oct}, pages={911–919} }
 @article{vaden_page_peters_cline_riviere_1993, title={Development and characterization of an isolated and perfused tumor and skin preparation for evaluation of drug disposition}, volume={53}, journal={Cancer Research}, author={Vaden, S. L. and Page, R. L. and Peters, B. P. and Cline, J. M. and Riviere, J. E.}, year={1993}, pages={101–105} }
 @article{vaden_williams_page_riviere_1993, title={EFFECT OF TUMOR PRESENCE ON CISPLATIN AND CARBOPLATIN - DISPOSITION IN THE ISOLATED, PERFUSED TUMOR AND SKIN FLAP}, volume={32}, ISSN={["0344-5704"]}, DOI={10.1007/BF00685873}, abstractNote={The purpose of this study was to evaluate the disposition of elemental platinum (Pt) derived from cisplatin (CDDP) or carboplatin (CBDCA) in the isolated, perfused tumor and skin flap (IPTSF). Flaps were perfused with either 3.0 micrograms CDDP/ml perfusion medium (n = 4 tumor, n = 4 control) or 15 micrograms CBDCA/ml (n = 4 tumor, n = 3 control) at a rate of 1 ml/min for 3 h. A 2-h (CDDP experiments) or 3-h (CBDCA experiments) washout phase using undosed medium was then performed. The disposition kinetics of free (ultrafilterable) Pt were characterized using a four-compartment physiologically relevant pharmacokinetic model. A tumor effect on the disposition of Pt was noted in that the Pt mass from CDDP in the central and mobile tissue compartments was greater in tumor flaps than in control flaps (P < 0.05). Similar trends were noted in CBDCA-treated flaps, but these were not significant. The Pt mass in the fixed tumor and non-tumor tissue compartments was significantly greater when Pt was derived from CDDP than when it was derived from CBDCA (P < 0.05). A linear relationship existed between the estimated micrograms of Pt in the flaps from both CDDP and CBDCA and the cross-sectional vascular resistance of the flaps at 30 (CDDP, r = 0.78; CBDCA, r = 0.89) and 60 min (CDDP, r = 0.65; CBDCA, r = 0.85) of perfusion. We conclude that the IPTSF is a useful model for evaluating the disposition of Pt drugs in tumor and non-tumor tissue and that tumor presence alters the disposition of CDDP.}, number={1}, journal={CANCER CHEMOTHERAPY AND PHARMACOLOGY}, author={VADEN, SL and WILLIAMS, PL and PAGE, RL and RIVIERE, JE}, year={1993}, month={Apr}, pages={31–38} }
 @article{dewoskin_page_riviere_1993, title={KIDNEY TRACE-METAL RESPONSE TO COMBINED CISPLATIN (CDDP) AND HYPERTHERMIA}, volume={9}, ISSN={["0265-6736"]}, DOI={10.3109/02656739309005050}, abstractNote={The effects of hyperthermia (HY) on cisplatin (CDDP) nephrotoxicity and kidney metal concentrations were evaluated in female F344 rats. Rats were anaesthetized with a xylazine/ketamine mixture, heated on a water-bed for 1 h to an intraperitoneal temperature of 41.1 +/- 0.2 degrees C, and maintained at hyperthermia for an additional 30 min (HY plateau). CDDP (5 mg/kg body weight) was administered at the start of the heating or at the HY plateau. Neither HY alone nor CDDP (5 mg/kg) at normothermia produced a significant effect on weight loss or nephrotoxicity. CDDP administered at the start of heating produced a moderate 1.5-fold increase in serum urea nitrogen (SUN) and serum creatinine concentrations. CDDP administered at the HY plateau produced a significant six-fold increase in SUN and a four-fold increase in creatinine concentration. Weight loss increased two- to three-fold from the combined regimen, but only the rats given CDDP at the HY plateau continued to lose weight through day 7. A loss of kidney copper (50-60%) resulted from the combined regimen, similar to losses observed with higher doses of CDDP at normothermia. HY alone had little effect on concentrations of kidney copper or zinc up to 4 days post-treatment. The results demonstrate that systemic hyperthermia significantly increases CDDP nephrotoxicity in F344 rats and that kidney copper loss from CDDP exposure at hyperthermia is similar to the loss observed from CDDP at normothermia.}, number={4}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={DEWOSKIN, RS and PAGE, RL and RIVIERE, JE}, year={1993}, pages={529–537} }
 @article{page_mcentee_george_williams_heidner_novotney_riviere_dewhirst_thrall_1993, title={Pharmacokinetic and Phase I Evaluation of Carboplatin in Dogs}, volume={7}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.1993.tb01013.x}, DOI={10.1111/j.1939-1676.1993.tb01013.x}, abstractNote={Thirty dogs with spontaneously occurring malignant neoplasms were treated monthly with carboplatin (CBDCA) given as a 30‐minute intravenous infusion in a dose escalation study. Twenty‐eight dogs were considered evaluable for toxicity. The maximally tolerated dose of CBDCA was conceptually defined as that dose, determined by logistic regression analyses of toxicity data, resulting in a 50% incidence of moderate toxicity (MOD50) or a 5% incidence of severe toxicity (SEV5). Each designated maximally tolerated dose was calculated for the first course of treatment only and for the first and second courses of treatment combined to estimate cumulative drug toxicity. The MOD50 and SEV5 for the first treatment course were 340 and 278 mg/M2, respectively. MOD50 and SEV5 values for the first plus second treatment courses were 327 and 231 mg/M2, respectively. The nadir of neutrophil and platelet counts occurred approximately 14 days after treatment. The mean neutrophil and platelet values for all dogs experiencing myelosuppression during the first two treatment courses were 1541/μL and 62,600/μL, respectively. Nonparametric pharmacokinetic analysis of plasma CBDCA values suggested that half‐life (T1/2), area‐under‐the‐curve and total body clearance (CLb) were not dose dependent. Volume of distribution (VDss) significantly increased with dose only between 100 and 150 mg/M2, not between 150 and 300 mg/M2. Dose‐independent serum CBDCA pharmacokinetic disposition indicates that detailed investigation of tissue CBDCA distribution would be warranted and may identify novel dosing strategies that could improve the therapeutic index of CBDCA by minimizing toxicity. (Journal of Veterinary Internal Medicine 1993; 7:235–240. Copyright © 1993 by the American College of Veterinary Internal Medicine.)}, number={4}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Page, Rodney L. and McEntee, Margaret C. and George, Steven L. and Williams, Patrick L. and Heidner, Greta L. and Novotney, Carol A. and Riviere, Jim E. and Dewhirst, Mark W. and Thrall, Donald E.}, year={1993}, month={Jul}, pages={235–240} }
 @article{page_1993, title={Recent advances in hyperthermia [therapeutic]}, volume={15}, number={6}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Page, R. L.}, year={1993}, pages={781} }
 @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} }
 @article{riviere_page_aucoin_rogers_williams_1991, title={EFFECT OF HYPERTHERMIA ON THE INVITRO HYDROLYSIS OF MELPHALAN}, volume={7}, ISSN={["0265-6736"]}, DOI={10.3109/02656739109005017}, abstractNote={The pharmacokinetics of melphalan was investigated at 37 degrees C and 42 degrees C in vitro in canine and porcine plasma to assess heat-induced changes in the in vivo rate of melphalan hydrolysis. Melphalan concentrations were assayed using HPLC. Rate of spontaneous hydrolysis of melphalan at 42 degrees C was increased 1.5-fold in canine and 1.9-fold in porcine plasma. These results should be considered when interpreting in vivo disposition studies.}, number={3}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={RIVIERE, JE and PAGE, RL and AUCOIN, DP and ROGERS, RA and WILLIAMS, PL}, year={1991}, pages={527–529} }
 @article{price_page_fischer_levine_gerig_1991, title={Efficacy and Toxicity of Doxorubicin/Cyclophosphamide Maintenance Therapy in Dogs with Multicentric Lymphosarcoma}, volume={5}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.1991.tb03131.x}, DOI={10.1111/j.1939-1676.1991.tb03131.x}, abstractNote={Doxorubicin/cyclophosphamide were evaluated as maintenance drugs for dogs with multicentric lymphosarcoma (n = 28). Median remission time of all dogs was 173 days. Remission duration was shorter, however, in dogs with stage IV/V disease, in dogs with pretreatment hypoalbuminemia, and in dogs that had received glucocorticoids before initiation of chemotherapy (P < 0.04). Nineteen dogs were evaluable for toxicity. Dose‐limiting gastrointestinal toxicosis was observed in three dogs, neutropenia was observed in three dogs, and cardiomyopathy was observed in three dogs. The doxorubicin/cyclophosphamide protocol described in this report is safe and effective in treating canine multicentric lymphosarcoma. Clinical stage, pretreatment steroid therapy, and hypoalbuminemia are prognostic factors for response to this protocol}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Price, G. Sylvester and Page, Rodney L. and Fischer, Bernard M. and Levine, Jay F. and Gerig, Thomas M.}, year={1991}, month={Sep}, pages={259–262} }
 @article{tyczkowska_page_riviere_1990, title={DETERMINATION OF CARBOPLATIN IN CANINE PLASMA BY LIQUID-CHROMATOGRAPHY WITH ULTRAVIOLET VISIBLE DETECTION AND CONFIRMATION BY ATOMIC-ABSORPTION SPECTROSCOPY}, volume={527}, ISSN={["0378-4347"]}, DOI={10.1016/S0378-4347(00)82130-1}, number={2}, journal={JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS}, author={TYCZKOWSKA, K and PAGE, RL and RIVIERE, JE}, year={1990}, month={May}, pages={447–453} }
 @inproceedings{page_riviere_heidner_mcentee_thrall_1989, title={Effect of temperature on cisplatin (CDDP) and carboplatin (CBDCA) pharmacokinetic disposition in dogs}, volume={2}, booktitle={Conference Proceedings}, author={Page, R. L. and Riviere, J. E. and Heidner, G. L. and McEntee, M. C. and Thrall, D. E.}, year={1989}, pages={499–501} }
 @article{riviere_page_dewhirst_tyczkowska_thrall_1986, title={Effect of hyperthermia on cisplatin pharmacokinetics in normal dogs}, volume={2}, DOI={10.3109/02656738609004965}, abstractNote={In vitro and in vivo cisplatin pharmacokinetic studies were conducted at 37 degrees C and 42-43 degrees C in dogs. Cisplatin at 1, 2, 3, 4 and 5 micrograms/ml was incubated with canine serum at 37 degrees and 43 degrees C. Aliquots were processed immediately for atomic absorption spectrophotometry to determine total as well as free, ultrafilterable cisplatin concentrations. Thirteen healthy, average-sized mongrel dogs received 1 mg/kg cisplatin as an intravenous bolus. Four were maintained unanaesthetized at 37 degrees C, two were anaesthetized and maintained at 37 degrees C and seven were anaesthetized and maintained at a rectal temperature of 42 degrees C for 60 min. Serum samples were obtained and processed for free and total cisplatin. There were no detectable concentration effects present in either in vitro group. The rate constant reflecting the decay of free cisplatin at 37 degrees C was 0.0035 +/- 0.0007 min-1 and increased significantly (P less than 0.0001) to 0.0053 +/- 0.001 min-1 at 43 degrees C. In vivo pharmacokinetic analysis consisted of model-independent parameters (total body clearance, volume of distribution, half-life and mean residence time). A significant increase (P less than or equal to 0.05) in all parameters was observed with free-cisplatin at 42 degrees C. This data would indicate that at the elevated temperatures encountered in whole body hyperthermia, the rate of formation of reactive metabolites from parent cisplatin is increased.(ABSTRACT TRUNCATED AT 250 WORDS)}, journal={International Journal of Hyperthermia}, author={Riviere, J. E. and Page, R. L. and Dewhirst, M. W. and Tyczkowska, K. and Thrall, D. E.}, year={1986}, pages={351–358} }