Table 3.
Pharmacological approach to pancreatic cancer cachexia.
| Drugs | Mechanism of action | References | Level of evidence |
|---|---|---|---|
| Progestogens (megestrol acetate and medroxyprogesterone acetate) | Appetite stimulation Decrease production and release of cytokines (IL-1, IL-6, TNF-α) Stimulation of NPY Decrease production of serotonin in PBMC | Bruera et al., 1990; Loprinzi et al., 1990, 1993a,b; McCarthy et al., 1994; Mantovani et al., 1998a,b; Westman et al., 1999; Deutsch and Kolhouse, 2004; Pascual López et al., 2004; Leśniak et al., 2008 | I |
| Corticosteroids (prednisone, dexamethasone, methylprednisolone) | Appetite stimulation Not well understood Likely from inhibition of IL-1, TNF-α, and leptin Stimulation of NPY | Willox et al., 1984; Bruera et al., 1985; Plata-Salamán, 1991; Loprinzi et al., 1999; | I |
| Cannabinoids (dronabinol) | Appetite stimulation, anti-emetic Interaction with endorphin receptors Interference with IL-1 synthesis Activation of cannabinoid receptor involved in the neurochemical circuit of leptin Inhibition of prostaglandin synthesis | Nelson et al., 1994; Jatoi et al., 2002 | II |
| NSAIDs (COX-2 inhibitors, indomethacin, ibuprofen) | Anti-inflammatory Decrease production and release of acute phase proteins and pro-inflammatory cytokines Inhibit prostaglandin synthesis | Gelin et al., 1991a,b; Lundholm et al., 1994; McMillan et al., 1995, 1997, 1999; Preston et al., 1995; Wigmore et al., 1995; Lai et al., 2008 | II |
| Thalidomide | Anti-inflammatory and immunomodulatory properties Downregulate production of TNF-α and other cytokines Inhibit NFκB Downregulate COX-2 Inhibit angiogenesis | Sampaio et al., 1991; Bruera et al., 1999; Gordon et al., 2005 | II |
| Omega-3 fatty acids (eicosapentaenoic acid) | Anti-inflammatory and immunomodulatory properties Decrease production of cytokines (IL-1, IL-6, TNF-α) Inhibit downstream effects of LMF and PIF | Tisdale and Beck, 1991; Meydani et al., 1993; Tisdale, 1996; Wigmore et al., 1996, 1997a, 2000b; Barber et al., 1999; Hussey and Tisdale, 1999; Jatoi et al., 2004; Fearon et al., 2006a | Conflicting |
NSAIDs, non-steroidal anti-inflammatory drugs; NPY, neuropeptide Y; IL-1, interleukin-1; IL-6, interleukin-6; TNF-α, tumor necrosis factor-alpha; PBMC, peripheral blood mononuclear cells; NFκB, nuclear factor κ B; COX-2, cyclooxygenase-2; LMF, lipid mobilizing factor; PIF, proteolysis-inducing factor.