Mathematical Analysis of a Mathematical Model of Chemovirotherapy: Effect of Drug Infusion Method

A mathematical model for the treatment of cancer using chemovirotherapy is developed with the aim of determining the efficacy of three drug infusion methods: constant, single bolus, and periodic treatments. The model is in the form of ODEs and is further extended into DDEs to account for delays as a result of the infection of tumor cells by the virus and chemotherapeutic drug responses. Analysis of the model is carried out for each of the three drug infusion methods. Analytic solutions are determined where possible and stability analysis of both steady state solutions for the ODEs and DDEs is presented. The results indicate that constant and periodic drug infusion methods are more efficient compared to a single bolus injection. Numerical simulations show that with a large virus burst size, irrespective of the drug infusion method, chemovirotherapy is highly effective compared to either treatments. The simulations further show that both delays increase the period within which a tumor can be cleared from body tissue.

[1]  C. Dolea,et al.  World Health Organization , 1949, International Organization.

[2]  P. Sibanda,et al.  Analysis of virotherapy in solid tumor invasion. , 2015, Mathematical biosciences.

[3]  G. Rustin,et al.  Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214). , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  J. Diallo,et al.  Intelligent Design: Combination Therapy With Oncolytic Viruses. , 2010, Molecular therapy : the journal of the American Society of Gene Therapy.

[5]  L. Aurelian Oncolytic virotherapy: the questions and the promise. , 2013, Oncolytic virotherapy.

[6]  Cancer report. , 1970, British medical journal.

[7]  A. Melcher,et al.  Cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances , 2016, Oncolytic virotherapy.

[8]  J. Usher,et al.  Some mathematical models for cancer chemotherapy , 1994 .

[9]  Delfim F. M. Torres,et al.  Enhancement of chemotherapy using oncolytic virotherapy: Mathematical and optimal control analysis. , 2018, Mathematical biosciences and engineering : MBE.

[10]  C. Yee,et al.  Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation , 2002, Nature.

[11]  K. Renee Fister,et al.  Mathematical model creation for cancer chemo-immunotherapy , 2009 .

[12]  Eugene V Koonin,et al.  Mathematical modeling of tumor therapy with oncolytic viruses: Regimes with complete tumor elimination within the framework of deterministic models , 2006, Biology Direct.

[13]  A. Surendiran,et al.  Oncolytic virotherapy – A novel strategy for cancer therapy , 2018, Egyptian Journal of Medical Human Genetics.

[14]  H. Jiang,et al.  Combination of the oncolytic adenovirus ICOVIR-5 with chemotherapy provides enhanced anti-glioma effect in vivo , 2007, Cancer Gene Therapy.

[15]  R. Carlson,et al.  Continuous infusion or bolus injection in cancer chemotherapy. , 1983, Annals of internal medicine.

[16]  R. Cattaneo,et al.  Mantle cell lymphoma salvage regimen: synergy between a reprogrammed oncolytic virus and two chemotherapeutics , 2010, Gene Therapy.

[17]  R. Ortíz-López,et al.  Oncolytic virotherapy. , 2008, Annals of hepatology.

[18]  Jianjun Paul Tian,et al.  The replicability of oncolytic virus: defining conditions in tumor virotherapy. , 2011, Mathematical biosciences and engineering : MBE.

[19]  Mark J. Ratain,et al.  Pharmacokinetic variability of anticancer agents , 2005, Nature Reviews Cancer.

[20]  M. Blagosklonny Overcoming limitations of natural anticancer drugs by combining with artificial agents. , 2005, Trends in pharmacological sciences.

[21]  Junjie Wei,et al.  Lytic cycle: A defining process in oncolytic virotherapy , 2013 .

[22]  E. Galanis,et al.  Clinical trial results with oncolytic virotherapy: a century of promise, a decade of progress , 2007, Nature Clinical Practice Oncology.

[23]  J L Boldrini,et al.  Optimal chemotherapy: a case study with drug resistance, saturation effect, and toxicity. , 1994, IMA journal of mathematics applied in medicine and biology.

[24]  H. I. Freedman,et al.  A mathematical model of vascular tumor treatment by chemotherapy , 2005, Math. Comput. Model..

[25]  Zeljko Bajzer,et al.  Modeling of cancer virotherapy with recombinant measles viruses. , 2008, Journal of theoretical biology.

[26]  Ordinary Differential Equations: A Practical Guide , 2011 .

[27]  P. Sibanda,et al.  Modelling the spatiotemporal dynamics of chemovirotherapy cancer treatment , 2017, Journal of biological dynamics.

[28]  A. Sonabend,et al.  Combination of adenoviral virotherapy and temozolomide chemotherapy eradicates malignant glioma through autophagic and apoptotic cell death in vivo , 2009, British Journal of Cancer.

[29]  S. Russell,et al.  History of oncolytic viruses: genesis to genetic engineering. , 2007, Molecular therapy : the journal of the American Society of Gene Therapy.

[30]  Herman Yeger,et al.  Combination therapy in combating cancer , 2017, Oncotarget.

[31]  D. Stringfellow Chemotherapy of viral infections , 2004, Archives of Dermatological Research.

[32]  S. Zamvil,et al.  Response to the RIF-1 tumor in vitro and in C3H/Km mice to X-radiation (cell survival, regrowth delay, and tumor control), chemotherapeutic agents, and activated macrophages. , 1980, Journal of the National Cancer Institute.

[33]  Y. Wan,et al.  Chemotherapy and Oncolytic Virotherapy: Advanced Tactics in the War against Cancer , 2014, Front. Oncol..

[34]  Frank Nani,et al.  A chemotherapy model for the treatment of cancer with metastasis , 2002 .

[35]  Dominik Wodarz,et al.  A dynamical perspective of CTL cross-priming and regulation: implications for cancer immunology. , 2003, Immunology letters.

[36]  D. Lyles,et al.  Early Steps of the Virus Replication Cycle Are Inhibited in Prostate Cancer Cells Resistant to Oncolytic Vesicular Stomatitis Virus , 2008, Journal of Virology.

[37]  M. Agarwal,et al.  Mathematical Modeling and Analysis of Tumor Therapy with Oncolytic Virus , 2011 .

[38]  G. Bosl,et al.  Carboplatin in clinical stage I seminoma: too much and too little at the same time. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  D. Wodarz,et al.  Viruses as antitumor weapons: defining conditions for tumor remission. , 2001, Cancer research.