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Model studies in adjuvant chemotherapy.

We have focused on three aspects of adjuvant chemotherapy applied to mice with one of the metastasizing tumors: Lewis lung carcinoma (LL) or mammary carcinoma 2661 (M2661). The first aspect concerned the timing of adjuvant chemotherapy. To investigate this, tumor-bearing mice were treated postoperatively with cyclophosphamide using a standard regimen. In M2661, adjuvant therapy was marginally effective in contrast to the clearly significant results obtained in LL. Any delay in the initiation of adjuvant therapy decreased the efficacy of the treatment. The effect of administering chemotherapy before surgery was also studied; normally, marginally effective adjuvant therapy was found to become effective when started preoperatively in M2661. In LL, effective adjuvant therapy was found to become less effective when started preoperatively. The second aspect considered was the comparability between the increase in relapse-free survival time and the increase in cure rate as alternate goals of adjuvant therapy. To study this, mice with small, medium, or large residual tumor loads were subjected to surgery and subsequently treated with cyclophosphamide. While the effect of adjuvant therapy on the cure rate increased proportionally with decreasing tumor load, the increase in lifespan in nonsurvivors was not related to tumor load. The final aspect of study was the selection procedure for drugs to be applied in adjuvant treatment in our models. Taking the volume response of large tumors as being predictive for the successful use of the same agent in adjuvant therapy, we obtained both false-negative and false-positive results in our tumor lines.