Comparison of the antitumor activity of gemcitabine and ara-C in a panel of human breast, colon, lung and pancreatic xenograft models

R. L. Merriman, L. W. Hertel, R. M. Schultz, P. J. Houghton, J. A. Houghton, P. G. Rutherford, L. R. Tanzer, G. B. Boder, G. B. Grindey

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Gemcitabine is a new deoxycytidine analog that exhibits significant cytotoxicity against a variety of cultured murine and human tumor cells. The cytotoxic action of gemcitabine appears to be due to the inhibition of DNA synthesis by inhibition of ribonucleotide reductase and by competition with dCTP for incorporation into DNA. We have previously shown that gemcitabine, but not cytosine arabinoside (ara-C), has a broad spectrum of antitumor activity against 7 different types of murine solid tumors. The activity of gemcitabine was schedule dependent. To further characterize its activity, gemcitabine was tested against 12 human carcinoma xenografts. When given on an every 3 day x 4 schedule, the following percent inhibitions (at maximally tolerated doses [MTD]; MTD/2) in tumor growth were seen: MX-1 mammary (93%; 80%), CX-1 colon (92%; 82%), HC-1 colon (96%; 92%), GC3 colon (98%; 94%), VRC5 colon (99%; 100%), LX-1 lung (76%; 61%), CALU-6 lung (75%; 38%), NCI-H460 lung (45%; 46%), HS766T pancreatic (73%; not tested), PaCa-2 pancreatic (69%; 40%), PANC-1 pancreatic (70%; 60%), and BxPC-3 pancreatic (9%; 19%). In contrast, only the LX-1 lung carcinoma xenograft was responsive to ara-C treatment, which inhibited tumor growth by a marginal 62 percent. Thus, like its activity against murine solid tumors, gemcitabine has excellent antitumor activity against a broad spectrum of human solid tumors.

Original languageEnglish (US)
Pages (from-to)243-247
Number of pages5
JournalInvestigational New Drugs
Volume14
Issue number3
DOIs
StatePublished - Nov 26 1996
Externally publishedYes

Keywords

  • Antitumor activity
  • Cytosine arabinoside
  • Gemcitabine
  • Xenograft

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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