Comparison of adjuvant chemotherapeutic activity against primary and metastatic spontaneous murine tumors.

Metastatic tumor incidence in BALB/C X DBA/8F1 female mice was examined in the presence and absence of adjuvant chemotherapy. Following surgical removal of spontaneous mammary adenocarcinomas, phenylalanine mustard, adriamycin, and 5-fluorouracil (PAF) were administered at 4, 2, and 50 mg/kg, respectively, once a week for six injections. Recurring tumors and new tumors developing in other breasts over the next 6 months were noted and surgically removed to allow time for originally undetectable pulmonary metastases to develop or to regress completely. This regimen of PAF significantly decreased original tumor recurrences from 58% in controls to 36% in treated mice. New tumor development also was significantly reduced during the 5 weeks of PAF therapy and for 8 weeks thereafter. However, the incidence of pulmonary metastasis was unaffected by the chemotherapy, being 42% in controls and 37% in PAF-treated mice. About 30% of these metastases would have been undetectable at the time of original surgery. The findings stress the importance of developing agents and/or schedules that will specifically affect metastatic cells when administered early to minimal numbers of tumor cells. This system represents a stringent clinimimetic model for evaluating adjuvant chemotherapy in this regard.