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

Objectives. Preclinical and clinical data have demonstrated the importance of schedule in optimizing the cytotoxic potential of topotecan, one of the most active agents in ovarian cancer. The availability of oral topotecan permits the exploration of the clinical utility of prolonged treatment programs employing this drug. Methods. Patients with platinum/taxane resistant ovarian and primary peritoneal cancers were treated with oral topotecan at an initial fixed dose of 1.5 mg/day for 5 days, followed by a 2-day break, with treatment continued on this schedule until disease progression or unacceptable toxicities. Results. Seven patients (median age 61) were entered into this phase 2 trial before further enrollment was discontinued due to the development of excessive side effects (grade 3: fatigue (n=3); emesis (n=1), thrombocytopenia with bleeding (n=1). Two additional patients noted grade 2 fatigue. Four patients experienced reductions in hemoglobin concentrations >4.0 g/dl from baseline during treatment, with two patients requiring red cell transfusions and two receiving recombinant erythropoietin. Three patients developed grade 3 neutropenia, while there were no episodes of greater than or equal tograde 2 diarrhea. Three patients exhibited biological evidence of an anti-neoplastic effect of therapy (>50% declines in serum CA-125 levels). Conclusion. Despite the strong theoretical appeal (as well as limited biological evidence of activity in platinum/taxane-refractory disease) associated with prolonging exposure of cycling ovarian cancer cells to topotecan, the specific oral regimen employed in this trial was associated with excessive bone marrow suppression, especially treatment-induced anemia, resulting in an unacceptable incidence of severe fatigue. (C) 2004 Elsevier Inc. All rights reserved.