Efficacy of a continuous, multiagent chemotherapeutic protocol versus a short-term single-agent protocol in dogs with lymphoma

Simón, Daniela; Moreno, Sol Naranjo; Hirschberger, Johannes; Moritz, Andreas; Kohn, Barbara; Neumann, Stephan; Jurina, Konrad; Scharvogel, Stefan; Schwedes, Claudia; Reinacher, M.; Beyerbach, Martin; Nolte, Ingo

doi:10.2460/javma.232.6.879

Cited by 53 publications

(61 citation statements)

References 23 publications

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“…Nevertheless, we can compare the clinical response rate with F14512 with the reported response rate with doxorubicin, which is commonly recognized as the most efficient single agent for the treatment of canine high-grade non-Hodgkin lymphoma. In a previous study (42), the response rate of dogs treated with doxorubicin as a first line agent was 74%, which can be compared with the result observed in our study (91%). Therefore, our results are promising and emphasize the potential of F14512, which could be investigated further either alone or in combination with other agents.…”

Section: Discussionsupporting

confidence: 63%

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: Discussionsupporting

confidence: 63%

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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“…26,27 Malignant lymphoma (ML) is the most common hematopoietic malignancy in dogs, caused by clonal proliferation of lymphocytes in solid tissue with distinctive morphologic and immunophenotypic features. The median age of occurrence is about 7 years, 28,29 and the aetiology is multifactorial (viral, genetic predisposition, etc.) with a positive association with exposure to herbicide, chemicals, and with living in highly polluted areas.…”

Section: Introductionmentioning

confidence: 99%

A Vaccine Targeting Telomerase Enhances Survival of Dogs Affected by B-cell Lymphoma

Peruzzi¹,

Gavazza

Mesiti³

et al. 2010

Molecular Therapy

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Canine cancers occur with an incidence similar to that of humans and share many features with human malignancies including histological appearance, tumor genetics, biological behavior, and response to conventional therapies. As observed in humans, the telomerase reverse transcriptase (TERT) activity is largely confined to tumor tissues and absent in the majority of normal dog tissues. Therefore, dog TERT (dTERT) can constitute a valid target for translational cancer immunotherapy. We have evaluated the ability of adenovirus serotype 6 (Ad6) and DNA electroporation (DNA-EP) to induce immune responses against dTERT in dogs affected by malignant lymphoma (ML). The vaccine was combined with standard chemotherapy regimen [cyclophosphamide, vincristine, prednisone (COP)]. dTERT-specific immune response was induced in 13 out of 14 treated animals (93%) and remained detectable and long-lasting with the absence of autoimmunity or other side effects. Most interestingly, the survival time of vaccine/Chemo-treated dogs was significantly increased over historic controls of Chemo-treated animals (>97.8 versus 37 weeks, respectively, P = 0.001). Our results show that Ad6/DNA-EP-based cancer vaccine against dTERT overcomes host immune tolerance, should be combined with chemotherapy, induces long-lasting immune responses, and significantly prolongs the survival of ML canine patients. These data support further evaluation of this approach in human clinical trials.

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“…A shorter but dose-intense CHOP chemotherapy schedule results in a median survival time of approximately 27 weeks [69]. Combination protocols have generally been in favor; however, single agent protocols have provided extended survival and should be considered [66,70].…”

Section: Lymphosarcomamentioning

confidence: 98%

“…The median age of occurrence is around 7 years [66,67]. The two standard-of-care treatments for canine B-2 lineage NHL are chemotherapy regimens: cyclophosphamide, vincristine and prednisolone (COP), and cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP).…”

Section: Lymphosarcomamentioning

confidence: 99%

The importance of comparative oncology in translational medicine

Riccardo

Aurisicchio²,

Impellizeri³

et al. 2014

Cancer Immunol Immunother

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Efficacy of a continuous, multiagent chemotherapeutic protocol versus a short-term single-agent protocol in dogs with lymphoma

Abstract: In this population of dogs, we were not able to identify any significant difference in remission or survival times between dogs with lymphoma treated with a continuous, multiagent chemotherapeutic protocol and dogs treated with a short-term single-agent protocol involving doxorubicin.

Cited by 53 publications

References 23 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

A Vaccine Targeting Telomerase Enhances Survival of Dogs Affected by B-cell Lymphoma

The importance of comparative oncology in translational medicine

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