Anti-tumor activity of CPT-11 in experimental human ovarian cancer and human soft-tissue sarcoma

Abstract

CPT‐11, a semi‐synthetic derivative of camptothecin, was investigated for its activity in panels of 15 human ovarian‐cancer lines and 10 human soft‐tissue sarcoma lines grown s.c. in nude mice. Various factors were analyzed that may be of influence on the extent of tumor‐growth inhibition induced by CPT‐11. At equitoxic doses, CPT‐11 was more effective in the daily ×5 schedule than the weekly ×2 schedule, although a 2‐fold higher dose was administered in the weekly ×2 schedule. Since i.p. and i.v. injections were similarly effective, the selected treatment schedule was 20 mg/kg i.p. daily ×5, starting when tumors measured approximately 150 mm3. Growth inhibition of ≥75% was obtained in 8/15 human ovarian‐cancer lines and in 6/10 human soft‐tissue sarcoma lines. A weak correlation was found between topoisomerase‐I mRNA in xenograft tissues and sensitivity to CPT‐11. Relative topoisomerase‐I expression was highest in MRI‐H‐207 and WLS‐160 xenografts, in which CPT‐11 was able to induce cures of all tumors. The high efficacy in the 2 panels of human tumor lines suggests over‐prediction of its potential clinical activity in these tumor types. The difference in efficacy of CPT‐11 between species may be related to the metabolism of the drug, since CPT‐11 is converted more efficiently into SN‐38 in mice. In addition, mice may be less sensitive to SN‐38‐induced side‐effects. On the basis of the preclinical data, frequent administration of lower doses of CPT‐11 should be considered in order to increase response rates in the clinic. Int. J. Cancer 73:891–896, 1997. © 1997 Wiley‐Liss, Inc.

Phase I Trial of Temozolomide and Protracted Irinotecan in Pediatric Patients with Refractory Solid Tumors

“…This schedule was chosen because multiple investigators have demonstrated the superior preclinical efficacy of irinotecan when given in smaller divided doses compared with large single infusions (9,(35)(36)(37)(38). In addition, this schedule was used in the xenograft studies of this drug combination (21,24) and has been shown to be feasible, safe, and active in the Phase I (10) and II (13) settings.…”

Cyclooxygenase inhibitors decrease the growth and induce regression of human esophageal adenocarcinoma xenografts in nude mice

“…The formula for Rt is (Vt/Vi) x 100, where Vi is the tumor volume at day 0. Tumor remission is considered when Rt = 50%; Rt = 51-75%: minimum regression; Rt = 76-125%: no variation; Rt > 125%: tumor progression (35,36).…”

Acetylsalicylic Acid Exhibits Antitumor Effects in Esophageal Adenocarcinoma Cells In Vitro and In Vivo

“…Tumor remission is considered when R t = 50 %; R t = 51-75 %: minimum regression; R t = 76-125 %: no variation; R t [ 125 %: tumor progression [18,19].…”