Metronomic chemotherapy (Proceedings)
The veterinary profession and more specifically, oncologists are taking an interest in the concept of metronomic chemotherapy. What is it? How does it work? Will it help pets with cancer? Metronomic chemotherapy (mCTx) is the use of very low doses of anticancer drugs given at a constant daily or alternate day schedule with no rest periods. Although there are no randomized clinical trials to prove that mCTx is effective in dogs and cats, there is enough research rationale to justify its use in veterinary medicine. In theory, mCTx given on a long term basis may help patients live longer achieving, durable stable disease. It may be effective in the inhibition of common mechanisms and pathways of malignancy such as angiogenesis, mitosis, and metastasis. Metronomic chemotherapy is a viable palliative option for veterinary cancer patients with resistant, inoperable or advanced cancer. Cancer patients that are entered into "Pawspice" (pet hospice) management programs may derive benefit from metronomic chemotherapy.
Metronomic Chemotherapy as an Option
The battle against cancer often involves initial skirmishes using surgery, chemotherapy or radiation therapy to make the cancer retreat into remission. Recurrences are fought along the way until the cancer claims the victim with its fatal agenda. In veterinary medicine, metronomic chemotherapy may be the best option to pursue in selected patients or in all patients depending on the disposition of the pet owner. Certainly when cancer recurs, the attending doctor and the family must regroup and evaluate the patient. Using the recommended framework for ethical decision making, as described in the over-treatment session in the previous hour would be very helpful http:// http://www.ethics.ubc.ca/people/mcdonald/conflict.htm. There comes a time when the pet's family declines previously successful standard recommendations such as salvage surgery, rescue chemotherapy or radiation therapy. The family may feel that the first round of treatments took a lot out of their pet and that the pet might not be able to handle further aggressive treatments. Other pet owners may feel that they just do not want to put their pet through the demands of another round chemotherapy again.The good news about metronomic chemotherapy is that it is very well tolerated by the majority of veterinary cancer patients due to its inherent low toxicity. (Liptack, et al, 2004) This author uses low dose, increased frequency therapy as a kinder, gentler way to help fragile and geriatric cancer patients with compromising comorbidities, dehydration, cachexia or malnourishment.
Antiangiogenesis Effect of mCTx
Metronomic chemotherapy is documented to target growing tumor vascular endothelial cells. Since it targets tumor vasculature, it may achieve an antiangiogenesis effect and stabilization of disease. Other agents which might also have antiangiogenic action such as NSAIDs and doxycycline are often added to mCTx protocols. This author has used oral antineoplastic agents such as Cytoxan™, Leukeran™, Xeloda™, Alkeran™ and lomustine along with various nutraceuticals such as Agaricus mushroom and Inositol Hexaphosphate in combination with NSAIDs and doxycycline to enhance overall anti-tumor effects. Some oncologists use chemo preventive agents such as Tamoxifen™ in combination with mCTx as well. Theoretically, mCTx incorporates an evidence based and scientific method of therapy, although the exact mechanisms of action are not fully understood.
Dogs and cats with resistant lymphoma or with families who cannot afford the routine chemotherapy protocols may receive metronomic chemotherapy, although the benefits are anecdotal and published data for benefit is lacking. It is important to know that using mCTx for lymphoma patients is not intended to induce remissions. It is best to use mCTx following induction protocols when the patient is in clinical remission. Using continuous low dose cytoxan, chlorambucil, melphalan, procarbazine, and/or dexamethasone may be helpful in sustaining longer remissions or partial remissions. It may help some patients achieve stable partial remissions. However, when the patient relapses; more aggressive drugs are required for re-induction.