cisplatin + cytarabine + hydroxyurea

This is a combination chemotherapy regimen consisting of three small molecule antineoplastic agents—cisplatin, cytarabine, and hydroxyurea. The combination is designed to exploit synergistic cytotoxic effects by targeting DNA synthesis and repair pathways in cancer cells. Cisplatin forms DNA crosslinks that inhibit DNA replication and transcription, leading to cell death. Cytarabine (Ara-C) is a nucleoside analog that inhibits DNA polymerase during the S-phase of the cell cycle, blocking DNA synthesis. Hydroxyurea inhibits ribonucleotide reductase, reducing deoxyribonucleotide pools required for DNA synthesis and repair. When used together, cytarabine and hydroxyurea can inhibit excision repair mechanisms for cisplatin-induced DNA damage, enhancing overall cytotoxicity against tumor cells[1][2]. This regimen has been studied in patients with refractory solid tumors such as non-small-cell lung cancer, breast carcinoma, glioblastoma, ovarian carcinoma, small-cell lung cancer, and mesothelioma[1]. Toxicities include significant but transient thrombocytopenia (especially in previously treated patients), nausea/vomiting/fatigue (expected), and potential nephrotoxicity due to synergistic effects[1].