Adjuvant postoperative chemotherapy with 5‐fluorouracil and methotrexate: Effect of schedule of administration on metastasis of 13762 mammary adenocarcinoma

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Abstract
Metastasizing mammary adenocarcinoma 13762 in female Fischer rats has been used as a model for studying postoperative adjuvant chemotherapy, using methotrexate (Mtx) and 5‐fluorouracil (5FU) either singly or in combinations. All animals that received postoperative adjuvant chemotherapy of 5FU alone, 5FU and Mtx simultaneously, or Mtx followed by 5FU had significant improvement of survivals. Methotrexate alone was ineffective in treating the visceral metastasis. The addition of Mtx at the time of 5FU administration actually decreased the therapeutic effectiveness of 5FU given by itself. Fluorouracil alone improved survival of rats with small or large tumors, whereas Mtx followed by 5FU was better than 5FU alone in rats with smaller tumors. Among all rats treated with chemotherapy, those rats that got Mtx followed by 5FU had the lowest amount of lung metastasis, and concomitant administration of nonspecific BCG immunotherapy delayed death from visceral metastasis only for rats receiving drugs according to this schedule.