Comparison of the antitumor activity of gemcitabine and ara-C in a panel of human breast, colon, lung and pancreatic xenograft models.
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.
Merriman
R L
RL
Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly & Co, Indianapolis, IN 46285, USA.
Hertel
L W
LW
Schultz
R M
RM
Houghton
P J
PJ
Houghton
J A
JA
Rutherford
P G
PG
Tanzer
L R
LR
Boder
G B
GB
Grindey
G B
GB
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003561:Cytarabine / Q000737:chemistry / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D015394:Molecular Structure; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D003841:Deoxycytidine; D000093542:Gemcitabine