Preoperative (neoadjuvant) chemotherapy in the murine Lewis lung carcinoma and possible implications for clinical use

The Lewis lung carcinoma, implanted in the footpad of BDF1 mice, was used for testing a preoperative chemotherapeutic treatment in comparison to a postoperative one, or to surgery alone. We administered both drugs effective in this model (Cyclophosphamide, Ifosfamide, CCNU), as well as ineffective ones (Ftorafur, Methyl-GAG, Vincristine) in order to study all the possible influences on the treatment outcome. In nine different experiments one active and one inactive drug were always compared in various schedules. Groups with surgery alone at an early or later stage were used as controls. The results showed that preoperative adjuvant treatment with an active drug decisively improved the survival time and the number of cured animals compared to surgery alone. The administration of an inactive drug and postponement of surgery decreased the number of cures, while the lifespan of the animals dying from lung metastases was not influenced. An improved treatment outcome compared to surgery alone resulted in cases where the preoperative inactive treatment was replaced by postoperative treatment with an active drug-a procedure also common and applicable for clinical practice. The body weight of the animals, noted as a sign of toxicity, was lowered when a cytostatic drug was used in addition to removal of the primary tumor. There was no difference between pre- or postoperative and repeated administrations. Based on these results preoperative adjuvant cytostatic treatment with histological control of response and decision for postoperative adjuvant treatment is recommended for clinical practice.