Combination chemotherapy with 5-fluorouracil and methyl-CCNU for the treatment of advanced gastrointestinal cancer.

Sixteen patients with advanced gastrointestinal cancer (colorectal 12/16, gastric 4/16) were treated with a combination of 5-fluorouracil (5-FU) plus 1-(2-chlorethyl)-3(4-methyl-cycloexyl)-1-nitrosourea (Me-CCNU). The therapeutic program consisted of orally administered Me-CCNU (140 mg/m2) and intravenous 5-FU (9.5 mg/kg by bolus injection for 5 days). The cycles were repeated at 6-week intervals. At the beginning of the therapy, 11/16 patients were in performance status (PS) 0-1 and 5 patients in PS 2-3. Eight patients developed early progressive disease between the 1st and 2nd course of therapy. Only a minor tumor response was observed in the remaining 50% of the patients. However, the patients with stabilized disease lived longer (11.8 months) than non-responders (3.5 months).

[In vitro evaluation of the chemosensitivity of an experimental murine leukemia rendered resistant in vivo to adriamycin]. / Valutazione in vitro della chemiosensibilita' di una leucemia sperimentale murina resa resistente in vivo alla adriamicina.

The results obtained using a rapid assay for in vitro chemosensitivity detection of leukemias are presented. The assay, performed according to the technique already described, involves in vitro incubation of a tumor cell suspension with various concentrations of antitumor drugs for 1 h and evaluation of drug-induced cell damage by addition to the cultured cells of 125I-deoxyuridine 48 h after pharmacological treatment. Results are expressed as percent inhibition of the isotope incorporation with respect to untreated controls. Preliminary results demonstrated that this assay is able to evidence differential chemosensitivity exhibited in vivo by murine leukemias. The present study reports the results obtained using comparatively P388 and P388/ADR, a subline of P388 murine leukemia with acquired resistance to Adriamycin in vivo. We found that P388/ADR exhibited resistance to ADR and DNR at all the concentrations tested, whereas P388 was highly sensitive. Cross-resistance of P388/ADR was also found to some structurally dissimilar agents, i.e. VCR and Act-D. These in vitro results correlate well with much data in the literature concerning the characteristics of resistance and cross-resistance exhibited in vivo by P388/ADR. These results suggest the possibility of using a similar in vitro assay for predicting the in vivo drug resistance of human leukemias.

[A short term test suitable for in vitro prediction of the drug sensitivity of human leukemias: a preliminary study on murine experimental neoplasms]. / Presentazione di un test a breve termine atto a predire "in vitro" la chemiosensibilita' di leucemie umane: studi preliminari su tumori sperimentali murini.

The present report provides information on the optimal assay conditions for evaluating chemosensitivity in vitro, as assessed by using murine leukemias and by correlating the in vitro results with the known chemosensitivity in vivo. The experiments were carried out with lymphocytic leukemias of DBA/2 origin, i.e.L1210 Cr and P388, maintained by weekly i.p. inoculation of 10(6) cells in histocompatible hybrid CD2F1 mice. Briefly, the assay involves in vitro incubation of leukemic cells with antitumor drugs for 1h at 37 degrees C and evaluation of drug-induced cell damage by adding to the cultured cells 125I-deoxyuridine at different times (3, 24, 48 and 72 hrs) after drug exposure. The results, expressed as percent inhibition of the isotope incorporation with respect to untreated controls, indicate that this assay may reflect the differential chemosensitivities exhibited in vivo by murine leukemias only on a 48-hr interval between drug treatment and 125IUdR uptake evaluation. These results suggest that a similar assay could be employed for predicting the chemosensitivity of human leukemias.