The chemosensitivity of 26 non-pretreated colorectal carcinomas (primary tumors and/or colorectal metastases) was studied by an in vitro antimetabolic assay, which evaluates the interference of drugs on the incorporation of 3H-thymidine and 3H-uridine in short-term cultures of human tumors. Our results correlate with the response rate obtained in clinical studies with monochemotherapy and justify the possibility of a future prospective study using individually tailored chemotherapy regimens. Doxorubicin-analogues, with an overall in vitro efficacy in 16.0 % and 14.3 % for 4-epidoxorubicin (epi-DX) and 4-deoxydoxorubicin (deo-DX), respectively, seem to deserve a modest role in the treatment of colorectal cancer, provided that a careful selection of patients is performed. Variability in anthracycline activity is indeed evident, also in our study, in relation to the different neoplastic picture of the various patients.
Get full access to this article
View all access options for this article.
References
1.
AjaniJ.A., KonojiaM.D., BodeyG.P.: Phase II evaluation of 4-epidoxorubicin in patients with metastatic colorectal carcinoma.Cancer Treat. Rep., 68: 1507–1508, 1984.
2.
ArmandJ.P., HurteloupP., FargeotP., KerbratP., RenardJ., HayatM., ChauvergneJ.: Phase II trial of esorubicin (4′-deoxydoxorubicin) in advanced colo-rectal cancer (abstract 422). 3rd ECCO Stockholm, June 16–20, 1985.
3.
ArmitageN.C., HardcastleJ.D.: Screening for colorectal cancer.Eur. J. Surg. Oncol., 11: 327–332, 1985.
4.
CostaA., PiazzaR., SanfilippoO., SilvestriniR.: A quantitative test for chemosensitivity of short-term cultures of human lymphomas.Tumori, 63: 237–247, 1977.
5.
DaidoneM.G., SilvestriniR., SanfilippoO., ZaffaroniN., VariniM., De LenaM.: Reliability of an in vitro short-term assay to predict the drug sensitivity of human breast cancer.Cancer, 56: 450–456, 1985.
6.
FalksonG., VorobiofD.A.: Epirubicin in colorectal cancer. In: Advances in Anthracycline Chemotherapy: Epirubicin.BonadonnaG. (ed.), pp. 105–109, Masson Italia Editori, Milano, 1984.
7.
FalksonG., VorobiofD.A.: Esorubicin in advanced colorectal cancer (abstract 421).3rd ECCO Stockholm, June 16–20, 1985.
8.
FerrazziE., NicolettoO., CarteiG., VinanteO., FornasieroA., RefattiF., FiorentinoM.V.: Phase II trial in advanced carcinoma (abstract).EORTC Symposium on treatment of advanced gastrointestinal cancer, Padova, Italy, June 1983.
GanzinaF.: 4′-Epidoxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data.Cancer Treat. Rev., 10: 1–22, 1983.
11.
HoldenerE.E., HansenH.H., HostH., CavalliF., RenardJ., SennH.J., PinedoH.M.: Phase II trial of 4′-epi-adriamycin in advanced colorectal cancer (abstract).Proc. Amer. Soc. Clin. Oncol., 2: 116, 1983.
12.
HoldenerE.E., CavalliF., HansenH.H., RenardJ., AbelR., RozencweigM., PinedoH.M.: Phase II trial of esorubicin in advanced colorectal cancer (abstract).ASCO, May 19–21, 1985.
13.
HoldenerE.E., HansenH.H., HostH., BruntschU., CavalliF., RenardJ., PinedoH.M., RozencweigM.: Epirubicin in colorectal cancer. A phase II study of the early clinical trials group (EORTC).Invest. New Drugs, 3: 63–66, 1985.
14.
KerbratP., Van der BurgM., BastitPh., FargeotP., MetzR., CholletPh., Van GlabbekM., AhyatM.: Phase II trial of esorubicin (4′-deoxydoxorubicin) in advanced colorectal cancer (abstract).UICC, August 21–27, 1986.
15.
KolarićK., PotrebicaV., CervekJ.: Phase II clinical trial of 4′-epidoxorubicin in metastatic solid tumor.J. Cancer Res. Clin. Oncol., 106: 148–152, 1983.
16.
Robustelli della CunaG., GanzinaF., PretiP., PavesiL.: 4′-Epidoxorubicin (4′-epi-DX) as single agent in advanced colorectal cancer (abstract).International Symposium: Advances in anthracycline chemotherapy: Epirubicin. Milanofiori Congress Centre Milan, Italy, June 10–12, 1984.
17.
SanfilippoO., DaidoneM.G., ZaffaroniN., SilvestriniR.: Development of a nucleotide precursor incorporation assay for testing drug sensitivity of human tumors. In: Predictive Drug Testing on Human Tumor Cells.HofmanV., MartzG. (eds.), pp. 127–139, Springer-Verlag, Berlin, 1984.
18.
SanfilippoO., SilvestriniR., ZaffaroniN., PivaL., PizzocaroG.: Application of an in vitro antimetabolic assay to human germ cell testicular tumors for the preclinical evaluation of drug sensitivity.Cancer, 1986 (in press).
19.
SchneiderC.: Determination of nucleic acids in tissue by pentose analysis. In: Methods in Enzymology.ColowickS.P., KaplanN.O. (eds.), pp. 680–684, Academic Press, New York, 1957.
20.
SilverbergE.: Cancer statistics, 1982, C.A.Cancer J. Clinicians, 32: 15–31, 1982.
21.
SilvestriniR., SanfilippoO., DaidoneM.G.: An attempt to use measurement of radioactive precursors incorporation to predict clinical response to treatment. In: Human Tumor Drug Sensitivity Testing in vitro Techniques and Clinical Applications.DendyP.P., HillB.T. (eds.), pp. 281–290, Academic Press, London, 1983.
22.
TewK.D., TaylorD.M.: The relationship of thymidine incorporation to use of fractional incorporation as a measure of DNA synthesis and tissue proliferation.Eur. J. Cancer, 14: 153–168, 1978.
23.
TismanG., HerbertV., EdlisH.: Determination of therapeutic index of drug by in vitro sensitivity tests using human host and tumor cell suspension.Cancer Chemother. Rep., 57: 11–19, 1973.
24.
VolmM., BruggemannA., GuntherM., KleineW., PfleidererA., Vogt-SchadenM.: Prognostic relevance of ploidy, proliferation, and resistance-predictive tests in ovarian carcinoma.Cancer Res., 45: 5180–5185, 1985.
