Skip to main content
SpringerLink
Log in

Flavone acetic acid distribution in human malignant tumors

  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

The pharmacokinetics of flavone acetic acid (FAA) after a dose of 4.8 mg/m2 given i. v. over 1 h was investigated in 13 patients with different solid tumors. The mean volume of distribution and clearance were 52 ± 4 l/m2 and 2.6 ± 0.2 l/h × m2, respectively. A tumor or metastasis biopsy was obtained from six patients 2 h after the end of infusion. Tumor FAA levels ranged from 39.6 to 148.8 µg/g and were similar to those obtained after a therapeutic i. v. dose of 200 mg/kg FAA in animals bearing Pan/03 tumor, which is very sensitive to the drug. Although FAA tumor concentration could be detected only during one interval and we therefore cannot draw a definitive conclusion, differences in the agent’s antitumor activity in mice and patients (i.e. very active in the former and inactive in the latter) are apparently not due to discrepancies in drug distribution and pharmacokinetics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bibby MC Double JA, Loadman PM (1988) Unique chemosensitivity of MAC 16 tumours to flavone acetic acid (LM 975, NSC 347512). Br J Cancer 58: 341

    PubMed  CAS  Google Scholar 

  2. Bibby MC, Double JA, Loadman PM, Duke CV (1989) Reduction of tumor blood flow by flavone acetic acid: a possible component of therapy. J Natl Cancer Inst 81: 216

    Article  PubMed  CAS  Google Scholar 

  3. Capolongo LS, Balconi G, Ubezio P, Giavazzi R, Taraboletti G, Regonesi A, Yoder OC, D’Incalci M (1987) Antiproliferative properties of flavone acetic acid (NSC 347512) (LM 975), a new anticancer agent. Eur J Cancer Clin Oncol 23: 1529

    Article  PubMed  CAS  Google Scholar 

  4. Chabot GG, Bissery MC, Corbett TH, Rutkowski K, Baker LH (1989) Pharmacodynamics and causes of dose-dependent pharmacokinetics of flavone-8-acetic acid (LM-975; NSC-347512) in mice. Cancer Chemother Pharmacol 24: 15

    PubMed  CAS  Google Scholar 

  5. Ching LM, Baguley BC (1987) Induction of natural killer cell activity by the antitumour compound flavone acetic acid (NSC 347512). Eur J Cancer Clin Oncol 23: 1047

    Article  PubMed  CAS  Google Scholar 

  6. Corbett TH, Bissery MC, Wozniak A, Plowman J, Polin L, Tapazoglou E, Dieckman J, Valeriote F (1986) Activity of flavone acetic acid (NSC-347512) against solid tumors of mice. Invest New Drugs 4: 207

    Article  PubMed  CAS  Google Scholar 

  7. Damia G, Zanette ML, Rossi C, Mandelli R, Ferrari A, D’Incalci M (1988) Dose-dependent pharmacokinetics of flavone acetic acid in mice. Cancer Chemother Pharmacol 22: 47

    Article  PubMed  CAS  Google Scholar 

  8. Damia G, Garofalo A, Rossi C, Giavazzi R, D’Incalci M (1989) Flavone acetic acid pharmacokinetics in nude mice. Eur J Cancer Clin Oncol (in press)

  9. Giavazzi R, Garofalo A, Damia G, Garattini S, D’Incalci M (1988) Response to flavone acetic acid (NSC 347512) of primary and metastatic human colorectal carcinoma xenografts. Br J Cancer 57: 27

    Google Scholar 

  10. Gouyette A, Kerr DJ, Kaye SB, Setanoians A, Cassidy J, Bradley C, Forrest G, Soukop M (1988) Flavone acetic acid: a nonlinear pharmacokinetic model. Cancer Chemother Pharmacol 22: 114

    Article  PubMed  CAS  Google Scholar 

  11. Hornung RL, Back TC, Zaharko DS, Urba WJ, Longo DL, Wiltrout RH (1988) Augmentation of natural killer activity, induction of IFN and development of tumor immunity during the successful treatment of established murine renal cancer using flavone acetic acid and IL-2. J Immunol 141: 3671

    PubMed  CAS  Google Scholar 

  12. Kerr DJ, Kaye SB, Cassidy J, Dutta S, Setanoians A, Forrest G, Cunningham D, Soukop M, Vezin WR (1985) A clinical pharmacokinetic study of LM985 and LM975. Br J Cancer 52: 467

    Google Scholar 

  13. Kerr DJ, Kaye SB, Cassidy J, Bradley C, Rankin EM, Adams L, Setanoians A, Young T, Forrest G, Soukop M, Clavel M (1987) Phase I and pharmacokinetic study of flavone acetic acid. Cancer Res 47: 6776

    PubMed  CAS  Google Scholar 

  14. Plowman J, Narayanan VL, Dykes D, Szarvasi E, Briet P, Yoder OC, Paull KD (1986) Flavone acetic acid: a novel agent with preclinical antitumor activity against colon adenocarcinoma 38 in mice. Cancer Treat Rep 70: 631

    PubMed  CAS  Google Scholar 

  15. Pratesi G, Manzotti C, Damia G, D’Incalci M (1988) Response of chemically induced primary colon tumours of the mouse to flavone acetic acid (NSC 347512). Br J Cancer 58: 144

    PubMed  CAS  Google Scholar 

  16. Urba WJ, Longo DL, Lombardo FA, Weiss RB (1988) Enhancement of natural killer activity in human peripheral blood by flavone acetic acid. J Natl Cancer Inst 80: 521

    Article  PubMed  CAS  Google Scholar 

  17. Wiltrout RH, Boyd MR, Back TC, Salup RR, Arthur JA, Hornung RL (1988) Flavone-8-acetic acid augments systemic natural killer cell activity and synergizes with IL-2 for treatment of murine renal cancer. J Immunol 140: 3261

    PubMed  CAS  Google Scholar 

  18. Zaharko DS, Grieshaber CK, Plowman J, Cradock JC (1986) Therapeutic and pharmacokinetic relationships of flavone acetic acid: an agent with activity against solid tumors. Cancer Treat Rep 70: 1415

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centro di Riferimento Oncologico, Aviano (Pordenone), Italy

    Andrea Freschi, Roberto Sorio, Alessandra Braida, Michele Quaia & Silvio Monfardini

  2. Divisione di Otorinolaringoiatria, Ospedale di Pordenone, Italy

    Giuseppe Caruso

  3. Istituto di Ricerche Farmacologiche ‘Mario Negri’, via Eritrea, 62, I-20157, Milan, Italy

    Giovanna Damia & Maurizio D’Incalci

Authors
  1. Giovanna Damia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrea Freschi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roberto Sorio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alessandra Braida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giuseppe Caruso
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michele Quaia
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Silvio Monfardini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maurizio D’Incalci
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Damia, G., Freschi, A., Sorio, R. et al. Flavone acetic acid distribution in human malignant tumors. Cancer Chemother Pharmacol 26, 67–70 (1990). https://doi.org/10.1007/BF02940298

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02940298

Keywords

Search

Navigation