Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study

Abstract

Systemic syndromes characterized by a persistent activity of circulating mediators (cytokines) are frequently present with advanced cancer. We grouped under the general heading of "Systemic Immune-Metabolic Syndrome (SIMS)" a particular variety of distressing systemic syndrome characterized by dysregulation of the psycho-neuro-immune-endocrine homeostasis, with overlapping clinical manifestations. SIMS may include cachexia, anorexia, nausea, early satiety, fatigue, tumor fever, cognitive changes and superinfection. The aim of this study was to ameliorate some of the SIMS symptoms in a homogeneous group of lung adenocarcinoma patients using a multitargeted therapy. Fifteen patients with evidence of SIMS were studied. SIMS was defined as the presence of weight loss, anorexia, fatigue performance status>/=2 and acute-phase protein response. Patients received medroxyprogesterone (MPA) (500 mg twice daily), celecoxib (200 mg twice daily), plus oral food supplementation for 6 weeks. After treatment, 13 patients either had stable weight (+/- 1%) or had gained weight. There were significant differences in improvement of body-weight-change rate, nausea, early satiety, fatigue, appetite and performance status. Patients who had any kind of lung infection showed higher levels of IL-10 compared to non-infected patients (P=0.039). Our results suggest that patients with advanced lung adenocarcinoma, treated with MPA, celecoxib and dietary intervention, might have considerable improvement in certain SIMS outcomes. This multitargeted symptomatic approach deserves further study.

A Phase II Study with Antioxidants, Both in the Diet and Supplemented, Pharmaconutritional Support, Progestagen, and Anti-Cyclooxygenase-2 Showing Efficacy and Safety in Patients with Cancer-Related Anorexia/Cachexia and Oxidative Stress

“…We believe that at the dosage (200 mg/d) and for the duration (4 months) used in our study, the treatment can be considered completely safe. In a recent study carried out on 15 patients with CACS treated with medroxiprogesterone acetate (500 mg twice daily) and celecoxib (200 mg twice daily) plus oral food supplementation for 6 weeks, an increase of body weight and an improvement in fatigue, appetite, and performance status (27) were observed.…”

Randomized Phase III Clinical Trial of Five Different Arms of Treatment in 332 Patients with Cancer Cachexia

“…In selecting the agents, we had originally planned to include the most selective cyclo-oxygenase 2 inhibitor, celecoxib, on the basis of the results observed in our phase II study [16] and in other authors' studies [61][62][63]; however, we eventually decided to not include this drug because of cardiotoxicity safety concerns that emerged in 2005 and that led to the withdrawal of rofecoxib from the market and restriction on the use of celecoxib.…”

Outcome research in palliative care: could it represent a new dimension of clinical research or clinical practice?

“…Indeed, to date progestins are considered the standard treatment of cancer cachexia, and both in our review of 15 randomized trials, and in the more recent study of Pascual Lopez et al, their role emerged in appetite improvement as well as in body weight gain [22,26]. However, both our review and the trials following our report failed to find any correlation between cachexia-related symptoms (weight and appetite loss) and quality of life, and the actual outcome of a treatment of cancer cachexia remains undefined [5,6,8,15,22]. Likewise, even the study of Pascual Lopez et al, besides its aims, does not demonstrate an improvement in quality of life with megestrol acetate, underlining some relevant methodological limits in quality of life assessment in randomized clinical trials in palliative care [26].…”