In vitro chemoresistance testing in well-differentiated carcinoid tumors.
BACKGROUND
Well-differentiated, "typical" carcinoid tumors traditionally have a very poor response to chemotherapy. We hypothesized that tumor specimens from well-differentiated carcinoid tumors would be highly resistant to the effects of chemotherapy when tested against a variety of antineoplastic agents in vitro.


METHODS
Ninety-eight typical carcinoid specimens were surgically harvested, cultured, and tested against antineoplastics in vitro. (3)H-Thymidine incorporation was used to assess the percentage of cell-growth inhibition (PCI) of tested specimens. PCI was used to determine if specimens had extreme drug resistance (EDR), intermediate drug resistance (IDR), or low drug resistance (LDR) to each reagent against which they were tested.


RESULTS
Seventy specimens generated results. Each was tested with an average of six drugs. The mean proportions of drugs classified as LDR, IDR, and EDR were 0.48 (range 0-1), 0.34 (range 0-1), and 0.18 (range 0-0.80), respectively. The mean numbers of drugs per specimen exhibiting LDR, IDR, and EDR chemoresistance were 2.7, 2.1, and 1.2, respectively. 57 of 70 specimens (81%) had LDR to at least two drugs. 5-FU had the highest frequency of low chemoresistance at 69%, followed by doxorubicin at 67%. Low in vitro resistance to chemotherapeutics was prevalent among typical carcinoids, while EDR was comparatively infrequent.


CONCLUSIONS
This implies that there may be less clinical chemoresistance and more chemosensitivity among typical carcinoid tumors than clinical trials have previously revealed. These findings warrant additional investigations assessing the response of carcinoid tumors to assay-guided chemotherapy regimens.
Lyons
John M
JM
Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. jlyons@lsuhsc.edu
Abergel
Jeffrey
J
Thomson
Jessica L
JL
Anthony
Cathy T
CT
Wang
Yi-Zarn
YZ
Anthony
Lowell B
LB
Boudreaux
J Philip
JP
Strauchen
James
J
Idrees
Muhammad
M
Warner
Richard R P
RR
Woltering
Eugene A
EA
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002276:Carcinoid Tumor / Q000188:drug therapy* / Q000556:secondary; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000473:pathology; D002454:Cell Differentiation; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008297:Male; D011379:Prognosis
D000970:Antineoplastic Agents