Sequence-dependent modulation of anticancer drug activities by 7-ethyl-10-hydroxycamptothecin in an HST-1 human squamous carcinoma cell line.
BACKGROUND
We studied the modulatory effects of 7-ethyl-10-hydroxy-camptothecin (SN-38), an active metabolite of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin, on the antitumor activities of clinically important anticancer drugs including cisplatin (CDDP), 5-fluorouracil (5-FU), mitomycin C (MMC), etoposide (VP-16), and adriamycin (ADR).


METHODS
The HST-1 human carcinoma cells were treated with graded concentrations of these anticancer drugs either alone or in combination with IC50 concentration of SN-38, administered in several different treatment schedules, and antitumor activity was evaluated by the growth inhibition assay.


RESULTS
SN-38 potentiated the antitumor activity of CDDP in all schedules with a maximal effect observed with a simultaneous administration, while SN-38 enhanced the cytotoxicity of MMC, 5-FU, or VP-16 only in certain schedules. By contrast, SN-38 attenuated the anticancer effect of ADR in all schedules.


CONCLUSIONS
These results demonstrate that SN-38 may have the advantage of augmenting the anticancer activity in combination with CDDP, MMC, 5-FU, and VP-16, depending on the schedule of administration, and should thus be incorporated into the design of a clinical trial for obtaining maximal therapeutic synergy.
Masumoto
N
N
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nakano
S
S
Esaki
T
T
Tatsumoto
T
T
Fujishima
H
H
Baba
E
E
Nakamura
M
M
Niho
Y
Y
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D000077146:Irinotecan; D016685:Mitomycin / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D059004:Topoisomerase I Inhibitors; D016685:Mitomycin; D005047:Etoposide; D000077146:Irinotecan; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin