Cisplatin + Cyclophosphamide + Doxorubicin + Ftorafur

The drug combination "cisplatin + cyclophosphamide + doxorubicin + ftorafur" is a multi-agent chemotherapy regimen that has been used in clinical settings for treating various types of cancer. This combination appears to be a variation of chemotherapy regimens that include cisplatin, cyclophosphamide, and doxorubicin, with the addition of ftorafur (also known as tegafur), which is an analog of fluorouracil (5-FU). The search results indicate that this combination has been studied in clinical trials for breast cancer treatment. ## Mechanism of Action Each component of this combination has a distinct mechanism of action: 1. **Cisplatin** binds to the N7 position of purine in DNA and forms adducts, leading to altered DNA activity that triggers apoptosis. This DNA damage activates several signaling pathways including oxidative stress, upregulation of p53, MAPK, JNK, and Akt pathways. 2. **Cyclophosphamide** is an alkylating agent that works by interfering with DNA replication in rapidly dividing cells. 3. **Doxorubicin** (also known as Adriamycin) is an anthracycline antibiotic that intercalates between DNA base pairs and inhibits topoisomerase II, preventing DNA replication and RNA synthesis. 4. **Ftorafur** (tegafur) is a prodrug of 5-fluorouracil (5-FU) that inhibits thymidylate synthase, disrupting DNA synthesis and repair. ## Clinical Applications The search results mention this specific combination being used in a randomized trial for stage II breast cancer patients after radical mastectomy and axillary evacuation. In this study, the regimen was administered as follows: - Cyclophosphamide: 500 mg/m² - Doxorubicin: 40 mg/m² - Ftorafur: 20 mg/kg orally for days 1-14 - The cycle was repeated every fourth week for eight courses While the specific four-drug combination is not extensively documented in the search results, similar combinations of cisplatin with cyclophosphamide and doxorubicin (without ftorafur) have shown efficacy in treating: 1. Salivary gland carcinomas, with a 50% objective response rate 2. Urothelial tumors, with complete remission rates of 39% for pure transitional cell carcinoma and 25% for mixed tumors ## Toxicity Profile The combination chemotherapy regimens involving these agents are associated with significant toxicities: - Hematologic toxicity is common, with studies reporting 88% of patients developing granulocytopenia and 53% developing thrombocytopenia - Neutropenic fever occurred in 44% of patients in one study - Renal toxicity with increased serum creatinine was observed in 18% of patients - Gastrointestinal side effects can be severe, with one study reporting that 32% of patients discontinued treatment due to intolerable gastrointestinal side effects - The combination of radiotherapy with this chemotherapy regimen may increase the severity of hematological side effects The search results suggest that while this combination shows activity against various cancers, the increased response rates must be balanced against the significant toxicity profile.

Other names

Cisplatin + Cyclophosphamide + Doxorubicin + Tegafur