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Enhanced Therapeutic Effect of cis-Diamminedichloroplatinum(II) against Nude Mouse Grown Human Pancreatic Adenocarcinoma When Combined with 1-ß-D-Arabinofuranosylcytosine and Caffeine¹

Department of Pathology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103 [A. P. K., A. A. K.], and Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [A. Y.]

We demonstrated previously that the effect of cis-diammine-dichloroplatinum(II) (cisplatin) against pancreatic cancer was substantially enhanced by the addition to the chemotherapeutic regimen of 1-ß-D-arabinofuranosylcytosine and caffeine. To obtain information on the factors influencing tumor response to this combination treatment, we investigated two adenocarcinomas of the exocrine pancreas grown in the nude mouse, tumors Capan-1 and SW-1990. Tumor response to cisplatin, characterized by tumor regression and tumor growth arrest, was observed when it was given in the upper limits of tolerance (5 mg/kg). Caffeine and 1-ß-D-arabinofuranosylcytosine singly and in combination had no effect on tumor growth; neither did they influence the effect of cisplatin when combined singly with the latter. However, the triple combination of cisplatin, 1-ß-D-arabinofuranosylcytosine, and caffeine resulted in complete tumor regression. The enhancing effect of the triple combination depended on tumor sensitivity to cisplatin and the amount of cisplatin administered and required rather large amounts of caffeine. The present report indicates that certain combination regimens may enhance the therapeutic effect of cisplatin against pancreatic carcinoma.

¹ Supported in part by Grant CA-34159 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Department of Pathology, UMDNJ-New Jersey Medical School, 100 Bergen Street, Newark, NJ 07103.

Received 12/ 6/84. Revised 8/12/85. Accepted 8/22/85.