Principal Investigator

Co-Principle Investigator

Abstract

The evidence that antioxidant supplementation (AOS) reduces oxidative cellular damage in vivo is mixed, and the data demonstrating that AOS can exert any effects on the ability of chemotherapeutic agents to induce DNA damage or apoptosis in vivo is either not compelling or nonexistent. It is important that the benefit versus harm of AOS during chemotherapy be investigated. A double blind, placebo controlled randomized trial of the effects of daily supplementation with 400 IU of vitamin E (alpha tocopherol) and 250 mg vitamin C (ascorbic acid) in 200 companion animals receiving doxorubicin for the treatment of either non Hodgkin’s lymphoma (NHL) or osteosarcoma (OSA) is proposed. The goal of the proposed study is to determine the effect of AOS during chemotherapy on response to treatment as measured by disease free interval (DFI), overall survival and tolerance of treatment. In addition, we propose to determine how AOS given concurrently with chemotherapy affects antioxidant status, oxidative cellular damage and propensity for apoptosis induction during sequential cycles of treatment. The specific aims are:

1. To determine the effect of antioxidant supplementation during chemotherapy on treatment efficacy as measured by disease free interval and overall survival. For NHL, 80% of treated dogs undergo complete remission in response to doxorubicin, but relapse within one year. Following primary surgical treatment, over 50% of dogs administered doxorubicin for osteosarcoma experience metastatic disease within one year. Thus, it is feasible to determine the effects of AOS on DFI and survival during the time course of this study.
   
2. To determine the effects of concurrent antioxidant supplementation on hematologic and gastrointestinal toxicity as well as weight loss and quality of life. Using criteria analogous to those used in human subjects, canine cancer patients are routinely monitored for drug induced toxicity and quality of life throughout the course of chemotherapy.
   
3. To determine if concurrent antioxidant supplementation affects in vivo biologic markers of oxidative damage. This will be done prior to and during sequential cycles of chemotherapy. DNA damage and propensity for apoptosis will be assessed in lymphocytes obtained circulation immediately before and after each chemotherapy session. The overall status of lipid and protein oxidation will be assessed in urine specimens and plasma obtained at the same time points.
   Evidence both in support of and contraindicating the use of supplements can be cited. Due to the current lack of knowledge, many patients are making decisions about how to participate in their treatment with limited guidance and considerable uncertainty. This is an unacceptable situation and this study is proposed as a first step aimed at obtaining basic information about the effects of antioxidant supplementation during chemotherapy.