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Related Experiment Videos

S-phase modulation by irinotecan: pilot studies in advanced solid tumors.

N Ramnath1, N Khushalani, K Toth

  • 1Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. nithya.ramnath@roswellpark.org

Cancer Chemotherapy and Pharmacology
|June 11, 2005
PubMed
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This study investigated irinotecan (CPT-11) combined with antimetabolites in cancer patients. High-dose CPT-11 effectively increased tumor cell S-phase, supporting its use in combination chemotherapy.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • Irinotecan (CPT-11) has shown potential in preclinical models to increase tumor cell S-phase.
  • Understanding this effect in human tumors and its relationship with combination therapy is crucial.

Purpose of the Study:

  • To assess the S-phase-inducing effect of CPT-11 in advanced solid tumors.
  • To determine the optimal CPT-11 dose for this effect.
  • To compare immunohistochemistry (IHC) for cyclin A and DNA flow cytometry (FC) for S-phase evaluation.
  • To establish the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of CPT-11 preceding gemcitabine (GEM).

Main Methods:

  • Two studies were conducted: CPT-11 followed by 5-fluorouracil (5-FU) or gemcitabine (GEM).

Related Experiment Videos

  • Tumor biopsies were analyzed for S-phase using IHC for cyclin A and FC before and after CPT-11.
  • Dose escalation of CPT-11 was performed to find the MTD and dose-effect relationship.

    • Main Results:

    • CPT-11 at 80 mg/m(2) significantly increased S-phase by 137% via IHC for cyclin A.
    • Lower doses of CPT-11 (40 and 60 mg/m(2)) showed lesser S-phase increases.
    • CPT-11 followed by 5-FU was well-tolerated.
    • The MTD of CPT-11 given before GEM was 60 mg/m(2).

    Conclusions:

    • CPT-11 administration increases tumor cell S-phase in patients with advanced solid tumors.
    • IHC for cyclin A is a viable method for assessing CPT-11's S-phase-inducing effect.
    • The combination of CPT-11 with 5-FU or GEM shows potential for further clinical investigation, with established MTDs.