Preventing Colorectal Cancer Metastases following Surgical Removal of a Primary Tumor

None listed

: In the current study we aim at testing the safety and efficacy of our drug cocktail in patients undergoing excision of colorectal cancer. Both short-term outcomes (immune and endocrine indices), as well as 2-year recurrence rates will be assessed within patients. Specifically, we propose a phase II double blind clinical trial with two major arms: (I) placebo treatment, and (II) treatment with a cocktail of a B-blocker (propranolol – to block CAs) and a COX2 inhibitor (etodolac – to block PGs). A total of 206 patients will be recruited along a two year. The drug treatment will be given for a total of 20-day period, commencing five days before surgery, with no time overlap with adjuvant therapy, and independently of any other routine therapy. The drug treatment is planned for only 15 post-operative days to reduce potential side effects, and because most immunological and endocrine perturbations induced by surgery dissipate during this period. Immune and endocrine baseline levels will be established in a group of thirty healthy matched control subjects. Short-term endocrine and immune measures will include: serum levels of various cytokines; serum cortisol, CRP, VEGF levels; leukocyte subpopulations and their functional markers; and NK number and activity. All indices will be assessed repeatedly within subjects, using freshly drawn blood samples that will be collected twice before surgery (days -5 and on the morning of surgery), and on post-operative days 1 and 3. Resected malignant tumors and normal colonic tissue will be tested for CA and PG receptor expression. Clinical outcomes will include perioperative complication rate and narcotic use, and 2-year recurrence rate. We hypothesize that our 20-day pharmacological treatment will: (i) significantly improve the status of the endocrine factors before surgery (e.g., VEGF, CRP, MMP2, MMP9 & cortisol) and enhance CMI competence, (ii) significantly attenuate the profound postoperative suppression of CMI and improve the postoperative endocrine status, and (iii) increase the 3-year recurrence-free survival rate. We further hypothesize that the peri-operative status of some endocrine/immunological indices will predict the 3-year recurrence rate, and that the within-subject alterations in these indices, caused by surgery and/or our drug intervention, will further predict recurrence-free survival rate. Provided that this study will indicate promising outcomes, our long-term plan is to employ this intervention in a larger sample of cancer patients and assess overall long-term survival rates. Such a larger study, powered to exhibit 5-10% improved survival rates, would be justified provided significant improvements in CMI/endocrine indices and/or a trend toward improved 3-year recurrence-free survival rates.

No related papers found yet.