Methods to improve efficacy of intravesical mitomycin C: results of a randomized phase III trial.

BACKGROUND: Intravesical chemotherapy (i.e., placement of the drug directly in the bladder) with mitomycin C is beneficial for patients with superficial bladder cancer who are at high risk of recurrence, but standard therapy is empirically based and patient response rates have been variable, in part because of inadequate drug delivery. We carried out a prospective, two-arm, randomized, multi-institutional phase III trial to test whether enhancing the drug's concentration in urine would improve its efficacy. METHODS: Patients with histologically proven transitional cell carcinoma and at high risk for recurrence were eligible for the trial. Patients in the optimized-treatment arm (n = 119) received a 40-mg dose of mitomycin C, pharmacokinetic manipulations to increase drug concentration by decreasing urine volume, and urine alkalinization to stabilize the drug. Patients in the standard-treatment arm (n = 111) received a 20-mg dose without pharmacokinetic manipulations or urine alkalinization. Both treatments were given weekly for 6 weeks. Primary endpoints were recurrence and time to recurrence. Treatment outcome was examined by use of Kaplan-Meier analysis with log-rank tests. Statistical tests were two-sided. RESULTS: Patients in the two arms did not differ in demographics or history of intravesical therapy. Dysuria occurred more frequently in the optimized arm but did not lead to more frequent treatment termination. In an intent-to-treat analysis, patients in the optimized arm showed a longer median time to recurrence (29.1 months; 95% confidence interval [CI] = 14.0 to 44.2 months) and a greater recurrence-free fraction (41.0%; 95% CI = 30.9% to 51.1%) at 5 years than patients in the standard arm (11.8 months; 95% CI = 7.2 to 16.4 months) and 24.6% (95% CI = 14.9% to 34.3%) (P =.005, log-rank test for time to recurrence). Improvements were found in all risk groups defined by tumor stage, grade, focality, and recurrence. CONCLUSIONS: This study identified a pharmacologically optimized intravesical mitomycin C treatment with statistically significantly enhanced efficacy.

The assessment of obstruction in the newborn with unilateral hydronephrosis by measuring the size of the opposite kidney.

We measured the size of the normal kidney opposite a unilateral hydronephrotic kidney in infants to determine if compensatory changes occurred and could be used as a diagnostic test for defining or excluding obstruction. Comparison of subgroups of neonates with unilateral hydronephrosis or multicystic renal dysplasia to normal controls demonstrated that compensatory changes do occur in the normal kidney. Normal kidneys opposite obstructed hydronephrotic kidneys requiring surgery became larger than normal for age. Normal kidneys opposite nonobstructed poorly functioning hydronephrotic kidneys whose function rapidly improved were smaller than normal for age. These changes in renal growth by the normal newborn kidney reflect renal counterbalance, which is exaggerated in this age group and which may be used to corroborate rapid changes in renal function caused by the presence or absence of obstruction. By plotting serial measurements of normal renal length on a renal growth chart, the diagnosis of obstruction in newborn hydronephrosis can be facilitated and the clinical management of the patient improved.