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Sequence dependence of the antitumor and toxic effects of 5-fluorouracil and cis-diamminedichloroplatinum combination on primary colon tumors in mice

  • Original Articles
  • Toxicity, cis-Diammineedichloro-platinum, 5-FU, Colon Tumors
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Summary

Primary colon tumors of different sizes and malignancy, chemically induced by methylazoxymethanol in outbred CF-1 mice, were used to investigate the antitumor effects of 5-Fluorouracil (5FU) and cis-diammine-dichloroplatinum (DDP), given weekly i.v. as single agents or in combination. When single-drug chemotherapy was tested, DDP showed higher efficacy than 5FU. In fact, in two separate experiments a significant reduction (P(0.05) of tumor number (TN) and tumor burden was obtained by treatment with the optimal dose of DDP (4.5 mg/kg per injection) and not by that of 5FU (52 mg/kg). When the two drugs were combined (24-h interval), studies carried out on healthy mice treated weekly i.v. showed a lower toxicity with the same doses given in the sequence 5FU-DDP than in the opposite sequence. The two drugs, delivered in the sequence 5FU followed by DDP, statistically reduced the TN and total tumor burden compared to control mice (P(0.05). On the other hand, the same doses in the sequence DDP followed by 5FU did not attain significant tumor reduction. The sequence dependence of the activity and toxicity of the 5FU and DDP combination observed in this experimental model should be taken into account in the design of clinical trials.

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Abbreviations

MAM:

methylazoxymethanol acetate

5FU:

5Fluorouracil

DDP:

cis-diamminedichloroplatinum

TN:

tumor number

TTB:

total tumor burden

Ara-C:

cytosine-arabinoside

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Authors and Affiliations

  1. Division of Experimental Oncology B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian, 1, I-20133, Milan, Italy

    G. Pratesi, C. Manzotti & F. Zunino

  2. Division of Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian, 1, I-20133, Milan, Italy

    L. Gianni

Authors
  1. G. Pratesi
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  2. L. Gianni
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  3. C. Manzotti
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  4. F. Zunino
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Additional information

This work was partially supported by Grant N. 84.00746.44 of Finalized Project “Oncology” of CNR (Rome, Italy)

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Pratesi, G., Gianni, L., Manzotti, C. et al. Sequence dependence of the antitumor and toxic effects of 5-fluorouracil and cis-diamminedichloroplatinum combination on primary colon tumors in mice. Cancer Chemother. Pharmacol. 21, 237–240 (1988). https://doi.org/10.1007/BF00262777

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  • DOI: https://doi.org/10.1007/BF00262777

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