Preclinical and clinical data have d emonstrated the impor-tance of schedule in optimizing the c ytotoxic potential of topotecan,one of the most active age nts in ovarian cancer.The availability of oral topotecan p ermits the exploration of the clinical utility of prolonged tr eatment programs em-ploying this drug.Patients with pla tinum /taxane resistant ovarian and primary peritoneal cancers were treated with oral topotecan at an initial fixed dose of 1.5mg /day for 5days,followed by a 2-day break,with treatment contin-ued on this schedule until disease pr ogression or unac-ceptable toxicities.Seven patient s(median age 61)were entered into this phase 2trial before further enrollment was discontinued due to the development of excessive side ef-fects(grade 3:fatigue(n =3);emesis(n =1),throm-bocytopenia with bleeding(n =1).Two additional patients noted grade 2fatigue.Four patients experienced reductionsin hemoglobin concentrations >4.0g /dl from baseline during treatment,with two patients requiring red cell transfusions and two receiving recombinant erythropoietin.Three patients developed grade 3neu tropenia,while there were no episodes of≥grade 2diarrhea.Three patients exhibited biological evidence of an anti -neoplastic effect of therapy(>50%declines in serum CA -125levels).Despite the strong theoretical appeal(as well as limited biological evidence of activity in p latinum /taxane -re-fractory disease)associatedwith prolonging exposur e of cy-cling ovarian cancer cells to topote can,the specific oral regimen employed in this trial was associated with excessive bone marrow suppression,especiall y treatment -induced anemia,resulting in an unacceptabl e incidence of severe fatigue.