COMPARISON OF ADJUVANT CHEMOTHERAPEUTIC ACTIVITY AGAINST PRIMARY AND METASTATIC SPONTANEOUS MURINE TUMORS

Abstract

Metastatic tumor incidence in BALB/c .times. DBA/8 F1 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 6 injections. Recurring tumors and new tumors developing in other breasts over the next 6 mo. were noted and surgically removed to allow time for originally undetectable pulmonary metastases to develop or 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 wk of PAF therapy and for 8 wk thereafter. The incidence of pulmonary metastases 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.