Phase 2 trial of prolonged administration of oral topotecan in platinum/taxane-refractory ovarian, fallopian tube, and primary peritoneal cancers.

摘要: Abstract Objectives Preclinical and clinical data have demonstrated the importance of schedule in optimizing cytotoxic potential topotecan, one most active agents ovarian cancer. The availability oral topotecan permits exploration utility prolonged treatment programs employing this drug. Methods Patients with platinum/taxane resistant primary peritoneal cancers were treated at an initial fixed dose 1.5 mg/day for 5 days, followed by a 2-day break, continued on until disease progression or unacceptable toxicities. Results Seven patients (median age 61) entered into phase 2 trial before further enrollment was discontinued due to development excessive side effects (grade 3: fatigue (n = 3); emesis 1), thrombocytopenia bleeding 1). Two additional noted grade fatigue. Four experienced reductions hemoglobin concentrations >4.0 g/dl from baseline during treatment, two requiring red cell transfusions receiving recombinant erythropoietin. Three developed 3 neutropenia, while there no episodes ≥grade diarrhea. exhibited biological evidence anti-neoplastic effect therapy (>50% declines serum CA-125 levels). Conclusion Despite strong theoretical appeal (as well as limited activity platinum/taxane-refractory disease) associated prolonging exposure cycling cancer cells specific regimen employed bone marrow suppression, especially treatment-induced anemia, resulting incidence severe