27 February 2025 : Review article
Review of the Interactions Between Anesthetic Agents and Chemotherapeutic Agents in Cancer Cell Lines Studied In Vitro
Paweł Radkowski
ABCDEFG 1,2,3, Hubert Oniszczuk ABCDEF 4*, Justyna Opolska BCDEF 1, Mateusz Pawluczuk BCDEF 4, Marek Gowkielewicz DEF 5, Łukasz Grabarczyk CEFG 6
DOI: 10.12659/MSM.947071
Med Sci Monit 2025; 31:e947071
Introduction
Propofol
Ketamine
Thiopental and Etomidate
Interactions Between Volatile Anesthetics and Chemotherapeutics
Interactions Between Benzodiazepines and Chemotherapeutics
Interactions Between Muscle Relaxants and Chemotherapeutics
Effects of Cytostatic Agents on Neuromuscular Blockade
Conclusions
Future Directions
References
Table 1 Summary of interactions between drugs used in general anesthesia and anticancer drugs.
| Drug | Effect on chemotherapy | Effect of chemotherapy on the drug |
|---|---|---|
| Propofol | Reduces the effectiveness of cisplatin in glioblastoma.Increases the sensitivity of cisplatin in non-small cell lung cancer and cervical cancer.Increases the sensitivity of pancreatic cancer to gemcitabine | Possible increase in patient sensitivity to propofol during neoadjuvant therapy |
| Ketamine | Potential attenuation of CPIN (caused mainly by oxaliplatin, cisplatin, paclitaxel, bortezomib, vincristine)1 | No relevant data available |
| Thiopental and Etomidate | No relevant data available | No relevant data available |
| Volatile anesthetics (sevoflurane, desflurane, isoflurane) | Sevoflurane potentiated the effect of cisplatin to inhibit growth and invasion of lung adenocarcinoma.Sevoflurane increased the chemosensitivity to cisplatin of non-small cell lung adenocarcinoma.Sevoflurane increased viability, migratory capacity, and chemoresistance to cisplatin of renal cell carcinoma.Isoflurane increased prostate cancer resistance to docetaxel.Volatile anesthetics (sevoflurane, desflurane) intensified nausea and vomiting after chemotherapeutics | Neoadjuvant chemotherapy (oxaliplatin and tegafur) reduced MAC values for sevoflurane and desflurane in operated hepatocellular carcinoma patients.Neoadjuvant chemotherapy (oxaliplatin and Gio) decreased MAC-BAR values for sevoflurane in gastric cancer patients undergoing radical gastrectomy.Chemotherapeutics increased the risk of PONV occurring after volatile anesthetics (sevoflurane, desflurane) |
| Diazepam | Reduced effect of temozolamide against human glioma cells | Idelalisib increased diazepam concentration(potential impact of other drugs that affect the activity of CYP3A4 and CYP2C19) |
| Midazolam | No available data | Nilotinib, idelalisib, certinib increased midazolam concentration.Paclitaxel, crizotinib, and pazopanib can potentially increase midazolam coccentration2(potential impact of other drugs that affect the activity of CYP3A4) |
| Non-depolarizing muscle relaxants | Chemotherapy (CAF: cyclophosphamide, doxorubicin, 5-fluorouracil) delays the onset of myorelaxation, especially with cisatracurium | Non-depolarizing muscle relaxants require more frequent doses, have a delayed onset of action and a quicker cessation of the relaxation effect |
| Depolarizing muscle relaxants | No available data | Possible prolongation of paralysis in patients with atypical pseudocholinesterase activity and the effects of some cytostatics |
| Fentanyl | Increased cytotoxicity of paclitaxel and doxorubicin against oral epithelial carcinoma and breast cancer cell lines expressing ABCB1, increased hepatotoxicity of paclitaxel.Reduced apoptosis of non-small cell lung cancer cell lines induced by cisplatin* | Enzalutamide significantly impaired the fentanyl effect.Imatinib, nilotinib, ribociclib, idelalisib can potentially increase fentanyl concentration(potential impact of other drugs that affect the activity of CYP3A4 and CYP2D6)2 |
| Remifentanyl and sufentanyl | No available data | No available data (potential impact of drugs that affect the activity of CYP3A4) |
| Oxycodone | No avaliable data | Ribocyclib, aldesleukin, dasatinib, tamoxifen, imatinib, nilotinib can potentially increase oxycodone concentration.Icotinib and apatinib inhibited oxycodone metabolism. Enzalutamide significantly impaired the oxycodone effect (potential impact of other drugs that affect the activity of CYP3A4, CYP3A5 and CYP2D6)2 |
| Morphine | No avaliable data. | Nilotinib can potentially increase morphine toxicity.CBD potentiated the supraspinal antinociceptive effect of morphine3 |
| 1 Promising results have been obtained using ketamine topically in the form of a gel containing additionally baclofen and amitriptyline; 2 Require further confirmatory studies; 3 Due to the inhibition of p-gp (p-glycoprotein) and UGT1A1 (glucuronosyltransferase 1a1), which is involved in morphine transport and metabolism, respectively; 4 CBD is used to treat adverse symptoms associated with cancer and chemotherapy as well as, according to in vitro studies, is a promising therapeutic and adjuvant substance in the treatment of some cancers; 5 The strongest effect occurred when both drugs were administered directly into the brain ventricles. * Demonstrated in in vitro studies; ** demonstrated in in vivo studies. CPIN – chemotherapeutic-induced peripheral neuropathy; MAC – minimal alveolar concentration; MAC-BAR – minimal concentration of anesthetic necessary to block the autonomic response; PONV – postoperative nausea and vomiting; CYP3A4 – cytochrome P450 3A4; CYP2C19 – cytochrome P450 2C19; CYP3A5 – cytochrome P450 3A5; CTP2D6 – cytochrome P450 2D6; ABCB1 – ATP-binding cassette subfamily B member 1; CBD – cannabidiol. | ||