Toxicity ◊ Dose limiting. Cumulative myelosuppression, which may be severe and prolonged (particularly thrombocytopenia with unusual bleeding or bruising, black tarry stools, blood in urine or stools, pin-point red spots on skin). It may occur up to 8 weeks after initiation of therapy, and counts return to normal within 10 weeks after therapy stops, although in about 25% of episodes, counts do not recover. Severity of bone marrow depression varies and determines subsequent dosage of mitomycin.

Myelosuppression. ◊ Occasional. Chest pain, mild to moderate peripheral neuropathy, pulmonary reactions, stomatitis. ◊ Rare. Hemorrhagic cystitis, skin rash, anorexia, constipation. 28 ♦ Administration ◊ Supplied as 1- and 5-mL vials. ◊ Dose modification. According to hematologic toxicity or hepatic insufficiency. ◊ Dose. Use 30 mg/m2 once a week as a single agent. The same dose is used in combination therapy with cisplatin. B. Epipodophyllotoxins • General mechanism of action ♦ Unlike podophyllotoxin, these agents do not cause mitotic arrest by binding to microtubules.

Neurotoxicity C. Pyrimidine analogues • Fluorouracil (5-FU) ♦ Indications. Carcinomas of the breast, stomach, pancreas, colon, and rectum. ♦ Pharmacology ◊ Mechanism of action. 5-FU undergoes conversion to 5-FU-5â ²-monophosphate (5-F-UMP or 5-F-uridylate) either by reacting directly with 5â ²-phosphoribosyl-1-pyrophosphate (PRPP) in the salvage pathway for purines or by first being converted to 5-FU and then monophosphorylated in the salvage pathway for pyrimidines (5-F-UMP may be phosphorylated to the nucleoside triphosphate 5-F-UTP and then incorporated into RNA, where it may have an inhibitory effect).