POTENTIATION OF THE ANTIPROLIFERATIVE EFFECTS OF ANTICANCER DRUGS BY OCTREOTIDE IN-VITRO AND IN-VIVO

The somatostatin analogue octreotide (SMS 201-995) exerts potent anti- proliferative effects in a number of experimental cancer models. Here we report on the inhibitory effect of octreotide in combination with t he chemotherapeutic agents mitomycin C, doxorubicin, 5-fluorouracil, o r taxol on the growth of AR42J pancreatic cancer cells in vitro. The d ose-dependent anti-proliferative effects of mitomycin C, doxorubicin a nd taxol were synergistically enhanced by octreotide. Combinations of octreotide and 5-fluorouracil resulted either in additive or, at high concentrations of the chemotherapeutic agent, in synergistic interacti ons, Combined treatment with doxorubicin and octreotide was also studi ed for time dependency and potential efficacy in tumour-bearing animal s. Pretreatment (24 h) with doxorubicin resulted in clear synergy. How ever, pretreatment with octreotide 24 h prior to addition of doxorubic in resulted only in an additive interaction. It was shown in AR42J-tum our-bearing nude mice that the combination of doxorubicin and octreoti de was well tolerated. Tumour growth was inhibited to 9% of controls, compared with 44% in the doxorubicin alone arm (day 14 of treatment). Our in vitro and in vivo interaction studies suggest that octreotide p otentiates the effect of various chemotherapeutic agents in a synergis tic or additive manner.