Interactions of Analgesics with Cisplatin: Modulation of Anticancer Efficacy and Potential Organ Toxicity

Abstract

Cisplatin (CDDP), one of the most eminent cancer chemotherapeutic agents, has been successfully used to treat more than half of all known cancers worldwide. Despite its effectiveness, CDDP might cause severe toxic adverse effects on multiple body organs during cancer chemotherapy, including the kidneys, heart, liver, gastrointestinal tract, and auditory system, as well as peripheral nerves causing severely painful neuropathy. The latter, among other pains patients feel during chemotherapy, is an indication for the use of analgesics during treatment with CDDP. Different types of analgesics, such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDS), and narcotic analgesics, could be used according to the severity of pain. Administered analgesics might modulate CDDP’s efficacy as an anticancer drug. NSAIDS, on one hand, might have cytotoxic effects on their own and few of them can potentiate CDDP’s anticancer effects via inhibiting the CDDP-induced cyclooxygenase (COX) enzyme, or through COX-independent mechanisms. On the other hand, some narcotic analgesics might ameliorate CDDP’s anti-neoplastic effects, causing chemotherapy to fail. Concerning safety, some analgesics share the same adverse effects on normal tissues as CDDP, augmenting its potentially hazardous effects on organ impairment. This article offers an overview of the reported literature on the interactions between analgesics and CDDP, paying special attention to possible mechanisms that modulate CDDP’s cytotoxic efficacy and potential adverse reactions.

The optimum inhibitory effects of Alpha Interferon and Cisplatin in colon cancer, a comparative in vitro study

“…Hence the ANOVA results suggest that the percentage of inhibition of alpha interferon was significant. These findings are consistent with previous findings that indicate that alpha-interferon suppresses tumor growth in colon cancer [ 12 – 16 ]. The in vivo anticancer activity of alpha interferon is proven in other cancers.…”

Diclofenac Sensitizes Signet Ring Cell Gastric Carcinoma Cells to Cisplatin by Activating Autophagy and Inhibition of Survival Signal Pathways

“…DCF is also known as a non-selective Cox inhibitor and plays a role in the inhibition of prostaglandin synthesis, the inhibition of lipoxygenase enzymes and the activation of the nitric oxide–cGMP antinociceptive pathway [ 13 ]. Previous studies have reported that the use of NSAID in combination with chemotherapeutic drugs effectively potentiated anticancer efficacy [ 14 , 15 ]. Among these outcomes, DCF has been proven to be able to enhance the cytotoxicity of cisplatin in cancer cells [ 16 ].…”

Prodrug Approach: NSAID Conjugates of Platinum Compounds as Anti-Cancer Agents

“…Octahedral platinum is considered inert but the modification of the axial position can effectively be utilized for further design and development. Several studies were conducted by combining the platinum drugs with non-steroidal anti-inflammatory agents such as aspirin, ibuprofen, flurbiprofen, naproxen etc as axial ligands (77,78). The General structures of the platinum-NSAID prodrugs were given in figure 7.…”