ABSTRACT
BACKGROUND: Invasive dental treatment in patients exposed to antiresorptive and antiangiogenic drugs can cause medication-related osteonecrosis of the jaw (MRONJ). Currently, the exact pathogenesis of this disease is unclear. METHODS: In March 2022, Medline (Ovid), Embase (Ovid), Scopus, and Web of Science were screened to identify eligible in vitro studies investigating the effects of antiresorptive and antiangiogenic compounds on orally derived cells. RESULTS: Fifty-nine articles met the inclusion criteria. Bisphosphonates were used in 57 studies, denosumab in two, and sunitinib and bevacizumab in one. Zoledronate was the most commonly used nitrogen-containing bisphosphonate. The only non-nitrogen-containing bisphosphonate studied was clodronate. The most frequently tested tissues were gingival fibroblasts, oral keratinocytes, and alveolar osteoblasts. These drugs caused a decrease in cell proliferation, viability, and migration. CONCLUSIONS: Antiresorptive and antiangiogenic drugs displayed cytotoxic effects in a dose and time-dependent manner. Additional research is required to further elucidate the pathways of MRONJ.
Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Humans , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Denosumab/adverse effects , Diphosphonates/pharmacology , Diphosphonates/therapeutic use , Zoledronic Acid , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/therapeutic useABSTRACT
OBJECTIVES: The efficacy of a concomitant oxaliplatin/bolus 5-fluorouracil/leucovorin regimen in 123 heavily pretreated patients with advanced colorectal cancer was evaluated. Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and radiographically progressive cancer which failed to respond to between two and five prior treatment modalities were consented and enrolled. METHODS: Patients received oxaliplatin on day 1 of weeks 1, 3, and 5 of an 8-week cycle. 5-fluorouracil/leucovorin was administered on day 1 of weeks 1 through 6. RESULTS: Grade 3 to 4 toxicities were as follows: diarrhea 30%; vomiting 11%; hematologic < 3%; peripheral neuropathy 2.5%. Of the 101 patients evaluable for response, 7% achieved a partial response (median duration 4.25 mo), 1 patient achieved a minor response (7 mo), and 31% had stable disease (median duration 6.08 mo). The median time to progression was 3.6 months. CONCLUSION: This regimen in heavily pretreated patients with disseminated colorectal cancer is of modest benefit, often at the expense of considerable gastrointestinal toxicity. It appears that the use of oxaliplatin/bolus 5-fluorouracil/leucovorin is more toxic than oxaliplatin/infusional 5-fluorouracil and possibly less effective.
