A mathematical justification for metronomic chemotherapy in oncology

We mathematically justify metronomic chemotherapy as the best strategy to apply most cytotoxic drugs in oncology for both curative and palliative approaches, assuming the classical pharmacokinetic model together with the Emax pharmacodynamic and the Norton-Simon hypothesis.From the mathematical point of view, we will consider two mixed-integer nonlinear optimization problems, where the unknowns are the number of the doses and the quantity of each one, adjusting the administration times a posteriori.Mathematics Subject Classification: 93C15, 92C50, 90C30

Metronomic Chemotherapy for Metastatic Breast Cancer

Background: As disease control and quality of life play a leading role in metastatic breast cancer (MBC), metronomic chemotherapy (MCT) is gaining popularity alongside conventional chemotherapy (CCT) and targeted therapies. Summary: MCT, defined as continuous administration of low-dose chemotherapeutic agents, is accepted as a therapy that exerts its effects via immunomodulation, anti-angiogenesis and direct cytotoxic effects. Oral administration of MCT is safe, easy to handle, and allows for flexible drug dosing. Dose accumulations associated with non-tolerable side effects are rare, so the medication can be administered for longer periods of time. Patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic disease resistant to endocrine-based therapy and not requiring rapid tumor response are generally suitable for MCT. However, MCT may also be promising in patients with triple-negative and HER2-positive tumors without aggressive disease who prefer a lower toxicity profile compared to CCT. The most commonly used agents are cyclophosphamide (CTX), methotrexate (MTX), capecitabine (CAPE), and vinorelbine (VRL), whereby a combination of agents is frequently applied. Key Messages: Based on the growing body of evidence, MCT can be considered as a suitable treatment option in selected MBC patients. Nevertheless, there is an urgent need for randomized controlled trials comparing MCT with CCT, but also with best supportive care. Due to the multimodal mechanisms of action, the combination with targeted and immunological therapies may represent a new promising approach for the treatment of MBC.

Evaluation of solid tumor response to sequential treatment cycles via a new computational hybrid approach

The development of an in silico approach that evaluates and identifies appropriate treatment protocols for individuals could help grow personalized treatment and increase cancer patient lifespans. With this motivation, the present study introduces a novel approach for sequential treatment cycles based on simultaneously examining drug delivery, tumor growth, and chemotherapy efficacy. This model incorporates the physical conditions of tumor geometry, including tumor, capillary network, and normal tissue assuming real circumstances, as well as the intravascular and interstitial fluid flow, drug concentration, chemotherapy efficacy, and tumor recurrence. Three treatment approaches—maximum tolerated dose (MTD), metronomic chemotherapy (MC), and chemo-switching (CS)—as well as different chemotherapy schedules are investigated on a real tumor geometry extracted from image. Additionally, a sensitivity analysis of effective parameters of drug is carried out to evaluate the potential of using different other drugs in cancer treatment. The main findings are: (i) CS, MC, and MTD have the best performance in reducing tumor cells, respectively; (ii) multiple doses raise the efficacy of drugs that have slower clearance, higher diffusivity, and lower to medium binding affinities; (iii) the suggested approach to eradicating tumors is to reduce their cells to a predetermined rate through chemotherapy and then apply adjunct therapy.

Metronomic chemotherapy for advanced diffuse hepatocellular carcinoma in a dog

Primary liver tumors represent 0.6% to 1.3% of neoplasms in dogs. Hepatocellular carcinoma (HCC) is the most common liver tumor. It is divided into three morphological groups: massive, nodular and diffuse. The presumptive diagnosis is made through imaging tests, such as ultrasound, although confirmation is made by histopathology. Surgery remains the treatment of choice for massive tumors, but there is no standard treatment for nodular and diffuse forms. This study aimed to report a case of prolonged survival in a dog with diffuse HCC, treated with metronomic chemotherapy and palliative care including non-steroidal anti-inflammatory and low-dose naltrexone.