cisplatin + fluorouracil + hydroxyurea

The combination of cisplatin, fluorouracil (5-FU), and hydroxyurea is a chemotherapy regimen used primarily in the treatment of advanced cervical carcinoma and head and neck cancers. This combination has been studied extensively by the Gynecologic Oncology Group (GOG) and has shown efficacy in clinical trials[1][5]. The regimen typically involves cisplatin administered on specific days (such as Days 1 and 29 at 50 mg/m²), 5-fluorouracil given as a continuous infusion (often over 96 hours on Days 2-5 and 30-33), and hydroxyurea administered orally (such as 2.5 g/m² twice weekly)[1]. This combination is frequently used concurrently with radiation therapy to enhance treatment efficacy. In cervical cancer treatment, this combination has been compared to other regimens such as hydroxyurea alone or cisplatin plus fluorouracil without hydroxyurea[5]. For head and neck cancers, the combination has shown promising results when used with radiation therapy, with studies reporting 2-year disease-free survival rates of approximately 48.6% and overall survival rates of about 69.4%[4]. The primary mechanisms of action involve cisplatin's DNA cross-linking properties, 5-fluorouracil's inhibition of thymidylate synthase, and hydroxyurea's interference with DNA synthesis through ribonucleotide reductase inhibition. Together, these agents work synergistically to enhance radiation sensitivity and improve tumor control. Common toxicities associated with this regimen include hematologic effects (particularly leukopenia), gastrointestinal symptoms, and radiation-related side effects. The severity of these side effects sometimes necessitates dose adjustments or treatment delays[1][4]. This combination represents an important treatment option in the multimodal management of locally advanced cervical and head and neck cancers, particularly when concurrent radiation therapy is indicated.