Dose and schedule I play an r Important in the generation of toxicity t observed in humans with all previously examined epothilones. Various Zeitpl ne For epothilones were examined, the side effects that change with more or less success. The most troubling side effect is Neurotoxizit t Occurring with analogs of epothilone BX-912 B, but not dose-limiting with epothilone analogues D. This problem is often dose limiting treatment taxane. Most patients in published studies have been treated with an epothilone taxane or platinum compound and can therefore pre neuropathy have had clinical or subclinical. Previous studies have shown that Cpmax drug toxicity with th Neurotoxizit as t or Kardiotoxizit Can be correlated t. Therefore the Zeitpl Ne which distribute the drug over time, as a w Chentliche or t Possible pattern or L Through prolonged infusion time examined.
Patupilone Phase I studies have a variety of treatments with bolus 5 minutes given once a week, 6 to 9 weeks, or 3-4 weeks or once every three weeks or every day for 5 days reported ridiculed Ngerte infusion. Patupilone not demonstrated myelosuppression h Depends calendar. It has not been associated with hypersensitivity reactions associated and k Can with an infusion time is shorter than the taxanes are administered. In the w Chentlichen dosage, patients generally tolerated doses of 0. 5-1. 85 mg/m2 in week 6 of Annex 9th A 3 6 mg/m2, patients with grade Diarrh 3, Gel that a lower dose of 2 st. 5 mg/m2. Since diarrhea leads in the fourth week of treatment on the calendar, the plan was modifications ed to 3 w Chentliche treatments with 1 week break followed by most patients tolerate second 5 mg/m2.
Dose-limiting toxicity t was diarrhea. Other h INDICATIVE side effects with this system:. Nausea, vomiting, diarrhea and fatigue Few patients had grade 3 or 4 myelosuppression. A dose-finding study with doses 0th 3-8 mg/m2 every 3 weeks came at a dose of 6 mg/m2 for phase II studies. Dose-limiting toxicity t was Diarrh at a dose of 8 mg / m2. Other toxicity Th grade 3 fatigue, nausea and vomiting. Grade 2 peripheral neuropathy was observed in 3 of 42 patients. Despite doselimiting diarrhea, other studies obtained at a dose of 6 Ht. 5 to 11 mg/m2 to prevent non-small cell lung cancer with a diagram of the bowel diarrhea intense. The non-renal elimination of drugs with no evidence of accumulation after repeated doses.
The drug is metabolized by the enzyme carboxylesterse first BMS 310705 patupilone contrast to derive the second-generation water- Soluble. The drug was administered as a 15-minute infusion every 3 weeks or w Examined weekly for 3 weeks. No dose-limiting toxicity T was observed at 40 mg/m2. Dose-limiting toxicity of t Grade 4 Hyponatri Mie secondary R to nausea and vomiting, and grade 4 neutropenia occurred at 70 mg/m2. hypersensitivity reactions observed. Tier 1 common side effects included fatigue, hair loss, neuropathy, nausea, constipation, muscle pain, chills and joint pain. Partial responses to BMS 310705 were in a patient with ovarian cancer with 40 mg/m2 and one patient with bladder cancer were treated with 30 mg/m2 to a total of 59 patients were observed.