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. 1993 Aug;68(2):277–281. doi: 10.1038/bjc.1993.328

Pharmacology and antitumour effects of intraportal pirarubicin on experimental liver metastases.

L H Ramirez 1, J N Munck 1, C Bognel 1, Z Zhao 1, P Ardouin 1, M F Poupon 1, A Gouyette 1, P Rougier 1
PMCID: PMC1968574  PMID: 8347482

Abstract

Early liver metastases have a predominant portal blood supply. Intraportal (i.port.) vein administration of cytotoxics could theoretically achieve enhanced drug concentrations in tumour cells and be effective as adjuvant therapy after resection of colorectal carcinoma. Pirarubicin (which has a higher hepatic extraction than doxorubicin) was investigated on liver metastases of the VX2 rabbit tumour, which were of less than 2 mm in diameter 7 days after cells injection into the portal vein. To evaluate antitumour activity, 24 rabbits were randomised into three groups 7 days after implantation: (a) control, (b) i.v. pirarubicin, (c) i.port. pirarubicin at doses of 2 mg kg-1 in both groups. Portal infusions led to no hematological or hepatic toxicity. Pharmacokinetic parameters showed a significantly reduced systemic exposure after i.port. administration. Fourteen days after treatment, livers and lungs were analysed. The mean number (+/- s.d.) of tumour foci was (a) 8.62 (+/- 5.4), (b) 4.62 (+/- 3.2), (c) 2.25 (+/- 1.4) (P < 0.05 a vs c). The mean tumour area was (a) 6.31 (+/- 6.1), (b) 1.31 (+/- 2.2), (c) 0.43 (+/- 0.4 cm2) (P < 0.05 a vs c) and the percentage (95% C.I.) of rabbits with lung metastasis was: (a) 87.5% (47-99%), (b) 75% (35-97%), (c) 12.5% (3-52%) (P < 0.02 b vs c). Intraportal pirarubicin seems to be well tolerated and more efficient than i.v. administration, particularly in preventing extrahepatic dissemination.

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Selected References

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  1. Ackerman N. B. Experimental studies on the role of the portal circulation in hepatic tumor vascularity. Cancer. 1986 Oct 15;58(8):1653–1657. doi: 10.1002/1097-0142(19861015)58:8<1653::aid-cncr2820580813>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  2. Beart R. W., Jr, Moertel C. G., Wieand H. S., Leigh J. E., Windschitl H. E., van Heerden J. A., Fitzgibbons R. J., Jr, Wolff B. G. Adjuvant therapy for resectable colorectal carcinoma with fluorouracil administered by portal vein infusion. A study of the Mayo Clinic and the North Central Cancer Treatment Group. Arch Surg. 1990 Jul;125(7):897–901. doi: 10.1001/archsurg.1990.01410190095015. [DOI] [PubMed] [Google Scholar]
  3. Butler J. A., Trezona T. P., Nordestgaard A., State D. Hepatic artery versus portal vein and systemic infusion of fluorodeoxyuridine of rabbit VX-2 hepatic implants. Am J Surg. 1989 Jan;157(1):126–129. doi: 10.1016/0002-9610(89)90432-7. [DOI] [PubMed] [Google Scholar]
  4. Conway J. G., Popp J. A., Ji S., Thurman R. G. Effect of size on portal circulation of hepatic nodules from carcinogen-treated rats. Cancer Res. 1983 Jul;43(7):3374–3378. [PubMed] [Google Scholar]
  5. Daly J. M., Kemeny N., Sigurdson E., Oderman P., Thom A. Regional infusion for colorectal hepatic metastases. A randomized trial comparing the hepatic artery with the portal vein. Arch Surg. 1987 Nov;122(11):1273–1277. doi: 10.1001/archsurg.1987.01400230059011. [DOI] [PubMed] [Google Scholar]
  6. FISHER E. R., TURNBULL R. B., Jr The cytologic demonstration and significance of tumor cells in the mesenteric venous blood in patients with colorectal carcinoma. Surg Gynecol Obstet. 1955 Jan;100(1):102–108. [PubMed] [Google Scholar]
  7. Fidler I. J., Poste G. The cellular heterogeneity of malignant neoplasms: implications for adjuvant chemotherapy. Semin Oncol. 1985 Sep;12(3):207–221. [PubMed] [Google Scholar]
  8. Fielding L. P., Hittinger R., Grace R. H., Fry J. S. Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for colorectal adenocarcinoma. Lancet. 1992 Aug 29;340(8818):502–506. doi: 10.1016/0140-6736(92)91708-g. [DOI] [PubMed] [Google Scholar]
  9. Horio Y., Takahashi T., Kuroishi T., Hibi K., Suyama M., Niimi T., Shimokata K., Yamakawa K., Nakamura Y., Ueda R. Prognostic significance of p53 mutations and 3p deletions in primary resected non-small cell lung cancer. Cancer Res. 1993 Jan 1;53(1):1–4. [PubMed] [Google Scholar]
  10. Metzger U., Laffer U., Aeberhard P., Arigoni M., Arma S., Barras J., Egeli R., Martinoli S., Mueller W., Schweizer W. Randomized multicenter trial of adjuvant intraportal chemotherapy for colorectal cancer (SAKK 40/81). An interim report. Acta Chir Scand. 1990 Jun-Jul;156(6-7):467–474. [PubMed] [Google Scholar]
  11. Miller A. A., Schmidt C. G. Clinical pharmacology and toxicity of 4'-O-tetrahydropyranyladriamycin. Cancer Res. 1987 Mar 1;47(5):1461–1465. [PubMed] [Google Scholar]
  12. Munck J. N., Fourcade A., Bennoun M., Tapiero H. Relationship between the intracellular level and growth inhibition of a new anthracycline 4'O-tetrahydropyranyl-Adriamycin in Friend leukemia cell variants. Leuk Res. 1985;9(2):289–296. doi: 10.1016/0145-2126(85)90091-8. [DOI] [PubMed] [Google Scholar]
  13. Taylor I., Machin D., Mullee M., Trotter G., Cooke T., West C. A randomized controlled trial of adjuvant portal vein cytotoxic perfusion in colorectal cancer. Br J Surg. 1985 May;72(5):359–363. doi: 10.1002/bjs.1800720509. [DOI] [PubMed] [Google Scholar]
  14. Weiss L. Comments on hematogenous metastatic patterns in humans as revealed by autopsy. Clin Exp Metastasis. 1992 May;10(3):191–199. doi: 10.1007/BF00132751. [DOI] [PubMed] [Google Scholar]
  15. Wereldsma J. C., Bruggink E. D., Meijer W. S., Roukema J. A., van Putten W. L. Adjuvant portal liver infusion in colorectal cancer with 5-fluorouracil/heparin versus urokinase versus control. Results of a prospective randomized clinical trial (colorectal adenocarcinoma trial I). Cancer. 1990 Feb 1;65(3):425–432. doi: 10.1002/1097-0142(19900201)65:3<425::aid-cncr2820650309>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  16. Willett C. G., Tepper J. E., Cohen A. M., Orlow E., Welch C. E. Failure patterns following curative resection of colonic carcinoma. Ann Surg. 1984 Dec;200(6):685–690. doi: 10.1097/00000658-198412000-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wolmark N., Rockette H., Wickerham D. L., Fisher B., Redmond C., Fisher E. R., Potvin M., Davies R. J., Jones J., Robidoux A. Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02. J Clin Oncol. 1990 Sep;8(9):1466–1475. doi: 10.1200/JCO.1990.8.9.1466. [DOI] [PubMed] [Google Scholar]

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