Radiation therapy and cis-diammine-dichloroplatinum (II) in transplantable and primary murine bladder cancer

Preoperative radiation improves survival in advanced bladder cancer but the high failure rate, primarily due to distant metastases, suggests a need for adjuvant chemotherapy. The optimal drug might exhibit an additive effect with radiotherapy. Transitional cell carcinoma (TCC) induced in mice by FANFT closely resembles the human counterpart, and both primary and transplanted tumors were used to evaluate the possible additive effect of cis DDP and cyclophosphamide (CY), two drugs with activity in TCC, with radiation. One hundred C3H/He mice had 5 x 104 TCC cells placed in their right hind limbs and randomized into a control (20) and 8 treatment groups (10); 3600 rad, 3600 rad + CY, 3600 rad + cis DDP, 1500 rad + cis DDP, 1500 rad + CY, CY, and cis DDP. Chemotherapy was initiated on day 7 and continued every week x 3. Radiation, in 250 rad or 600 rad fractions, was given biweekly to the tumor bearing limb using a CO60 source. 3600 rad alone produced 60% cures with a significant reduction in average tumor diameter (p < 0.001). 3600 rad + cis DDP achieved 78% cures, the best regimen. Therapy of palpable tumors yielded similar results--ave. tumor diameter (D-38) for controls 16.5, 3000 rad--10.6 (p < 0.001), cis DDP--10.2, CY + 1600 rad--8.1, cis DDP + 300 rad--6.2. Cis DDP + 3000 rad was significantly better than cis DDP or 3000 rad alone. One hundred fifty mice ingesting FANFT for 11 months were randomized into 7 groups and subjected to the same regimens to evaluate the effect on primary tumors. The greatest reduction in tumor volume was in mice receiving 1500 rad + cis DDP (mean bladder weight, 29.68 vs. controls 53.57, p < 0.005). These results consistently suggest cooperation between irradiation and cis DDP. Adjuvant cis DDP for invasive bladder cancer might be maximized by initiation with preoperative radiotherapy. Our initial clinical data with cis DDP + irradiation in advanced TCC are encouraging