COMPARATIVE ACTIVITY OF ORAL AND PARENTERAL TOPOTECAN IN MURINE TUMOR-MODELS - EFFICACY OF ORAL TOPOTECAN

Studies were performed using several tumor models to determine the ora l efficacy of topotecan. These studies were direct comparisons of oral administration with parenteral treatment by the intravenous, intraper itoneal, or subcutaneous routes. Treatment schedules included bolus tr eatments at 4- or 7-day intervals and a split-dose regimen (q3hx4) rep eated at 4- or 7-day intervals. On the various schedules, the maximall y tolerated dose of topotecan was either equivalent to or at most 1.7- fold that of parenteral administration, indicative of excellent oral b ioavailability in the mouse. Orally administered topotecan was compara ble in efficacy to parenteral treatment in four of five tumor models t ested (i.v. L1210 leukemia, i.v. B16 melanoma, i.v. and s.c. Lewis lun g carcinoma). The M5076 reticulum cell sarcoma implanted i.p. responde d to i.p. and s.c. but not to orally administered topotecan. These stu dies provide convincing support for the clinical evaluation of orally administered topotecan.