Surgery – Miscellaneous – Methods
Reexamination Certificate
1998-10-22
2001-09-11
Isabella, David J. (Department: 3738)
Surgery
Miscellaneous
Methods
C604S500000
Reexamination Certificate
active
06286513
ABSTRACT:
BACKGROUND
Approximately 56,000 new cases of bladder carcinoma are diagnosed each year. Of the newly diagnosed cases, 75-85% are superficial tumors (Ta, T1 and Tis) and 15-25% are invasive tumors (T2-4). The primary treatment for superficial bladder carcinomas is transurethral resection, i.e., surgical removal of the tumor. Unfortunately, tumors recur in 40% to 80% of the patients who undergo transurethral resection. Among the patients with recurrent tumors, 10-20% suffer tumor progression, i.e., muscular invasion or metastasis. Drugs such as methotrexate, doxorubicin, or cisplatin are often administered systemically to patients with invasive or metastatic bladder carcinomas.
Recently, studies have been conducted to determine whether an adjuvant intravesical therapy would be useful for preventing tumor recurrence in patients with superficial bladder carcinomas. Intravesical therapy involves direct administration of a drug into the bladder of the patient following transurethral resection. The goal of adjuvant intravesical therapy is to eliminate the neoplastic and pre-malignant cells that are not removed by surgery.
A few studies have been conducted on the effect of intravesical administration MMC or bacillus Calmette Guerin (BCG). The customary experimental MMC intravesical therapy involved weekly administration of MMC at a dose of 1 mg/ml in 20-40 ml of water for six to eight weeks. These studies have shown that an additional 1-13% of the patients who received the customary experimental MMC intravesical therapy following transurethral resection did not display or have a recurrent tumor at 1 year as compared to patients who undergo transurethral resection alone. Thus, although it was possible to reduce tumor recurrence by the customary experimental MMC intravisical therapy, the improvement was relatively modest.
Accordingly, it is desirable to have a new adjuvant therapy for treating patients with superficial bladder carcinomas.
SUMMARY OF THE INVENTION
A new therapy useful for preventing tumor recurrence in patients with Ta, T1, and Tis transitional cell carcinoma is provided. The new therapy is an adjuvant intravesical therapy, i.e., it is employed on patients following transurethral resection of the Ta, T1, or Tis carcinoma. The new therapy, referred to hereinafter as the “high efficacy therapy” comprises the steps of reducing the volume of urine in the bladder of the patient to a value of about 10 ml or less; and then administering an aqueous solution containing at least 2 mg/ml of MMC to the bladder of the patient for a period of at least about 120 minutes. The volume of solution administered to the bladder of the patient is about 20 ml. Preferably, the high efficacy therapy is administered to the patient weekly for a period of at least six weeks. Preferably, the high efficacy therapy further comprises the step of reducing the amount of urine produced by the patient during the time MMC is administered to the patient to a value of 1 ml/min or less. Preferably, the high efficacy therapy further comprises the step of administering an alkalinizing agent such as, for example, sodium bicarbonate to the patient before the MMC dosing solution is administered to the patient. The alkalinizing agent is administered in an amount sufficient to increase the pH of the urine produced by the patient during the time of MMC administration to a value of about 6.5 or greater. Preferably, the alkalinizing agent is administered orally.
REFERENCES:
patent: 5252673 (1993-10-01), Hirano et al.
patent: 5301688 (1994-04-01), Stephan et al.
“Use of pharmacologic data and computer simulations to design an efficacy trial of intravesical mitomycin C therapy for superficial bladder cancer” by Wientjes, et al.,Cancer, Chemotherapy and Pharmacology,Feb. 17, 1993.
“Apparnt Failure of Current Intravesical Chemotherapy Prophylaxis to Influence the Long-Term Course of Superficial Transitional Cell Carcinoma of the Bladder” by Lamm, et al.,The Journal of Urology,vol. 153, 1444-1450, May 1995.
Eksborg S,et al.“Intravesical instillation of Adriamycin. A model for standardization of the chemotherapy”.Eur Urol. 1980;6(4):218-20.
Groos E,et al.“Iintravesical chemotherapy. Studies on the relationship between pH and cytotoxicity”.Cancer. Sep. 15 1986;58(6):1199-203.
Ilett KF,et al.“Effect of urine pH on the stability of doxorubicin and its recovery from bladder instillations”.Br J Urol. May 1990;65(5):478-82.
Jauhiainen K,et al.“Optimisimg mitomycin C activity during intravesical instillation”.Urol Res.1983;11(2):59-62.
Lamm DL,et al.“Apparent failure of current intravesical chemotherapy prophylaxis to influence the long-term course of superficial transitional cell carcinoma of the bladder”.J Urol.May 1995;153(5):1444-50.
Jauhiainen K,et al.“Intravesical cytostatics: pH-dependence of antitumour activity”.Urol Res.1985;13(1):19-21.
Rohde D,et al.“7-N-(2-([2-(gamma-L-glutamylamino)-ethyl]-dithio)-ethyl)-mitomycin C (KW-2149) is more active than mitomycin C on chemonaive and drug-resistant urothelial carcinoma cells”.Urol Res.1998;26(4):243-7.
Wientjes MG,et al.“Use of pharmacologic data and computer simulations to design an efficacy trial of intravesical mitomycin C therapy for superficial bladder cancer.”Cancer Chemother Pharmacol.1993;32(4):255-62.
Yen WC,et al.“Different pH dependency of mitomycin C activity in monolayer and three-dimensional cultures”.Pharm Res.Dec. 1996;13(12):1887-91.
Au Jessie L.-S.
Wientjes M. Guill
Au Jessie L.
Isabella David J.
Lahive & Cockfield LLP
Lauro, Esq. Peter C.
O'Hara Kelly
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