Continuous Low‐Dose Oral Chemotherapy for Adjuvant Therapy of Splenic Hemangiosarcoma in Dogs

Lana, Susan E.; U'Ren, Lance; Plaza, Susan; Elmslie, Robyn; Gustafson, Daniel L.; Morley, Paul S.; Dow, Steven

doi:10.1111/j.1939-1676.2007.tb03019.x

Cited by 124 publications

(140 citation statements)

References 33 publications

(38 reference statements)

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“…This consisted of a 3-hour F14512 i.v. infusion once daily for 3 consecutive days, repeated every 2 weeks (days 1-3, days 15-17, and days [22][23][24]. The first dose level of 0.05 mg/kg and the schedule of administration were chosen following previous preclinical studies performed in beagle dogs and to be consistent with ongoing and future clinical trials in humans.…”

Section: Treatment Schedulementioning

confidence: 99%

“…Etoposide has been extensively studied in dogs for pharmacokinetics (PK) and toxicologic purposes (20,21), but little data are available concerning its potential antitumor efficacy in pet dogs (22,23). A retrospective study on 13 dogs with relapsing lymphoma treated with etoposide (24) showed that etoposide had a minimal therapeutic effect.…”

Section: Introductionmentioning

confidence: 99%

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Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma

Tierny

Serres

Segaoula

et al. 2015

Clinical Cancer Research

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Purpose: F14512 is a new topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. F14512 is currently in a phase I/II clinical trial in patients with acute myeloid leukemia. The aim of this study was to investigate F14512 potential in a new clinical indication. Because of the many similarities between human and dog lymphomas, we sought to determine the tolerance, efficacy, pharmacokinetic/pharmacodynamic (PK/PD) relationship of F14512 in this indication, and potential biomarkers that could be translated into human trials. Experimental Design: Twenty-three dogs with stage III–IV naturally occurring lymphomas were enrolled in the phase I dose-escalation trial, which consisted of three cycles of F14512 i.v. injections. Endpoints included safety and therapeutic efficacy. Serial blood samples and tumor biopsies were obtained for PK/PD and biomarker studies. Results: Five dose levels were evaluated to determine the recommended dose. F14512 was well tolerated, with the expected dose-dependent hematologic toxicity. F14512 induced an early decrease of tumoral lymph node cells, and a high response rate of 91% (21/23) with 10 complete responses, 11 partial responses, 1 stable disease, and 1 progressive disease. Phosphorylation of histone H2AX was studied as a potential PD biomarker of F14512. Conclusions: This trial demonstrated that F14512 can be safely administered to dogs with lymphoma resulting in strong therapeutic efficacy. Additional evaluation of F14512 is needed to compare its efficacy with standards of care in dogs, and to translate biomarker and efficacy findings into clinical trials in humans. Clin Cancer Res; 21(23); 5314–23. ©2015 AACR.

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Section: Treatment Schedulementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma

Tierny

Serres

Segaoula

et al. 2015

Clinical Cancer Research

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“…8,11,13,14 Chemotherapy in the adjuvant setting has been evaluated in various clinical studies and has shown promise in prolonging life after surgical resection of the primary HSA lesion. [15][16][17][18][19] Most of those studies included dogs with different clinical stages of disease.…”

Section: Introductionmentioning

confidence: 99%

Treatment with DAV for Advanced-Stage Hemangiosarcoma in Dogs

Dervisis

Domı́nguez

Newman

et al. 2011

Journal of the American Animal Hospital Association

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Hemangiosarcoma (HSA) is an aggressive disease that is fairly common in the dog. The authors evaluated a doxorubicin, dacarbazine, and vincristine (DAV) combination protocol in dogs with nonresectable stage II and stage III HSA. Twenty-four dogs were enrolled in this prospective, phase 2 study. Doxorubicin and dacarbazine were administered on day 1 while vincristine was administered on days 8 and 15. The protocol was repeated every 21 days for a maximum of six cycles or until disease progression. Toxicity and efficacy were assessed by clinical and laboratory evaluation and by questionnaires completed by the owners. Of the 24 included dogs, 19 were evaluable for response. The response rate (including five complete responses and four partial responses) was 47.4%. Median time to tumor progression was 101 days and median overall survival was 125 days.Significant toxicities were noted, including 41 high-grade hematologic and 12 high-grade gastrointestinal toxic events.

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“…The fi rst full paper was not published for another 6 years [ 50 ]. It compared the outcome of nine dogs with splenic hemangiosarcoma treated with a traditional doxorubicin protocol dose-intense single-agent chemotherapy and nine dogs with the same disease treated with metronomic chemotherapy.…”

Section: Metronomic Chemotherapy In Dogsmentioning

confidence: 98%

Clinical Studies of Metronomic Chemotherapy in Dogs

Marchetti

Giorgi

2014

Metronomic Chemotherapy

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In the last decade metronomic chemotherapy has received increased interest in veterinary oncology. Indeed, low-dose metronomic chemotherapy has been shown an important stabilizing effect on cancer growth, conferring both prolonged clinical benefi ts and positive effects on the quality of life of patients. A number of studies have been performed in dogs on the effi cacy of metronomic dosing of various chemotherapeutic drugs. Metronomic chemotherapy is offered as the treatment of choice for all pets with malignant tumors where owners are reluctant to embark on an aggressive therapy protocol. It is indicated in patients with organ failure in which the toxicity of chemotherapy may be fatal as well as in patients with an aggressive nature that would require sedation for each parenteral administration. Metronomic therapy induces minimal impact on the animal; it is a low-cost alternative and it is easy to administer. Moreover, it has been recently recognized that dogs affected by natural cancer serve as unique animal model for human tumors. For this reason, the metronomic chemotherapy experience in dogs could lead to innovative and unexplored schedules for humans. It may be used as a more accurate model than rodents with induced cancers for the extrapolation of dose, effi cacy and safety profi les to humans.

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Continuous Low‐Dose Oral Chemotherapy for Adjuvant Therapy of Splenic Hemangiosarcoma in Dogs

Abstract: Continuous orally administered LDC may be an effective alternative to conventional high-dose chemotherapy for adjuvant therapy of dogs with HSA.

Cited by 124 publications

References 33 publications

Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma

Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma

Treatment with DAV for Advanced-Stage Hemangiosarcoma in Dogs

Clinical Studies of Metronomic Chemotherapy in Dogs

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