Myelosuppression topotecan

Topotecan inhibits topoisomerase I to cause single-strand breaks in DNA. The pharmacokinetics of topotecan can be described by a two-compartment model, with a terminal half-life of 80 to 180 minutes, with renal clearance accounting for approximately 70% of the clearance.19 Topotecan has shown clinical activity in the treatment of ovarian and lung cancer, myelodysplastic syndromes, and acute myelogenous leukemia. The intravenous infusion may be daily for 5 days or once weekly. Side effects include myelosuppression, mucositis, and diarrhea. 

Topotecan 1.5 mg/m2 IV infused over 30 minutes on days 1,2,3, 4, 5 repeat every 21 days or 4 mg/m2 IV infused over 30 minutes once a week for 3 consecutive weeks, followed by 1 week rest 6.5%—1 7% 31% Myelosuppression (DLT), nausea/vomiting, diarrhea, Stomatitis, abdominal pain, alopecia, SGOT/SGPT elevation 1. Give proper dosing for renal dysfunction... 

Topotecan Inhibits topoisomerase I Small cell lung cancer, ovarian cancer Nausea and vomiting Myelosuppression... 

Irinotecan is a prodrug that is converted mainly in the liver by the carboxylesterase enzyme to the SN-38 metabolite, which is 1000-fold more potent as an inhibitor of topoisomerase I than the parent compound. In contrast to topotecan, irinotecan and SN-38 are mainly eliminated in bile and feces, and dose reduction is required in the setting of liver dysfunction. Irinotecan was originally approved as second-line monotherapy in patients with metastatic colorectal cancer who had failed fluorouracil-based therapy. It is now approved as first-line therapy when used in combination with 5-FU and leucovorin. Myelosuppression and diarrhea are the two most common adverse events. There are two forms of diarrhea an early form that occurs within 24 hours after administration and is thought to be a cholinergic event effectively treated with atropine, and a late form that usually occurs 2-10 days after treatment. The late diarrhea can be severe, leading to significant electrolyte imbalance and dehydration in some cases. 

Gemtuzumab ozogamicin (Mylotarg) consists of a humanized anti-CD33 monoclonal antibody conjugated to the cytotoxic enediyne antibiotic calicheamicin. It has been used to treat a subset of patients with acute myeloid leukemia in association with topotecan -I- cytarabine. Its most common adverse effects are myelosuppression, increased hepatic enzyme activity, infections, fever and chills, bleeding, nausea and vomiting, and dyspnea. 

Myelosuppression, neutropenia, and to a lesser extent thrombocytopenia, are dose-limiting toxic effects of topotecan. Reversible non-cumulative neutropenia usually occurs at between days 8 and 15 after an intravenous dosage of 1.5 mg/m on five consecutive days. The nadir of the neutrophil count occurs on day 11, with recovery on day 21. Neutropenia, with cell counts less than 1.5 x lO /l (grade 2) and 0.5 x 10 /1 (grade 4), is observed in 70-97% of patients. In addition, 4-33% of patients treated with conventional dosages of topotecan develop neutropenic fever (97-99). 

Co-administration of cisplatin before topotecan has a sequence-dependent effect on the disposition of topotecan. Cisplatin-related acute changes in glomerular filtration rate can temporarily alter topotecan clearance, causing more severe myelosuppression. Nevertheless, this sequence has been recommended in clinical trials, based on its high antineoplastic efficacy. Patients therefore have to be monitored closely when the two agents are given together (154). 

E Myelosuppression (primarily neutropenia) is the dose-limiting side effect of topotecan. The median nadir occurs at about 11 days, with a duration of 7 days. Total alopecia may occur with topotecan but is not considered dose limiting. Nausea and vomit-... 

Up to the end of 1995, many results of phase II clinical studies on CPT-11 and topotecan administered intravenously have been presented and summarized [183, 184, 187,188]. In phase II studies of CPT-11 against solid tumours, the most popular dosage schedules were 100 mg/m /day once weekly or 150 mg/m /day once every 2 weeks in Japan, 125 mg/m /day once weekly in U.S.A., and 350 mg/m /day once every 3 weeks in Europe. On the other hand, topotecan was infused for 30 min at doses of 1.25-2.0 (dominantly 1.5) mg/m /day once for 5 consecutive days every 3 weeks. Usually, the dose-limiting toxicity of CPT-11 is myelosuppression (mainly neutropenia)... 

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