Chemoimmunotherapy of murine bladder cancer

The lethality of invasive transitional cell carcinoma (TCC) has prompted a search for effective, minimally toxic, adjuvant therapy. Such agents were evaluated in a murine bladder cancer (MBT2) model which parallels the clinical disease. One hundred C3H/He mice were inoculated i.d. with 2.5 x 10⁴ viable MBT2 tumor cells and randomized to receive either normal saline (control), cis-platinum (CPT), cyclophosphamide (CY), methotrexate (MTX), BCG, (CY + MTX), or (CY + MTX + BCG). Chemotherapy was given intraperitoneally weekly starting on day 7 after inoculation. Immunotherapy was given intralesionally on days 1 and 10 only. All mice were treated for 5 weeks followed by 5 weeks of observation. At 5 weeks, tumors of mice receiving cyclophosphamide alone or either of the combinations of therapy were smaller (P < 0.01) than tumors of controls or other single agents alone. Each regimen increased survival, but only the combination regimen increase survival significantly (P < 0.01). In the doses and schedule used in this model, combination chemotherapy and chemoimmunotherapy significantly delay tumor growth and increase duration of survival (P < 0.01) when compared with controls or single agent groups.