zinostatin and Carcinoma--Transitional-Cell

Topics: Antibiotics, Antineoplastic; Carcinoma, Transitional Cell; Clinical Trials as Topic; Humans; Male; Middle Aged; Urinary Bladder Neoplasms; Zinostatin

The cytotoxicity and antitumor effects of zinostatin (NCS) were examined under various conditions of pH using cultured HeLa cells and a transplantable tumor line of WKA rats. The cytotoxicity of NCS against HeLa cells was highly dependent on the pH at ranges of 6-8. When HeLa cells were treated with 0.075 microgram/ml of NCS, the survival rate was about 1% at pH 6.0, while it was near 90% at pH 7.4 and pH 8.0. Even at pH 6.5-6.75, the survival rate was about 50% lower than that seen with pH 7.4 and pH 8.0. The ratio of the dose of NCS for a 90% cell mortality at pH 6.0 to that at pH 7.4 was less than one-seventh. Antitumor effects were assessed by local intra-arterial infusion against tumors 4 or 9 days after inoculation of 10(6) RBT-1 tumor cells into the thigh of rats. When NCS (0.7 mg/kg) in phosphate-buffered saline (PBS) (pH 7.4) or 5 mM lactate (about pH 3.0) was administered, the ratio of average tumor weight about 2 weeks after treatment (tumor weight of the rats given NCS in PBS/tumor weight of the rats given NCS in lactate) was 3.2 or 1.7 for the rats treated 4 or 9 days after tumor inoculation, respectively. Lactate or PBS alone had no effect on the growth of tumor. After treatment there was no difference in body weight change between the group treated with NCS in lactate and the group treated with NCS in PBS. We conclude that the cytotoxicity of NCS was potentiated under acidic conditions, both in vitro and in vivo.

Topics: Animals; Antibiotics, Antineoplastic; Body Weight; Carcinoma, Transitional Cell; Cell Survival; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Synergism; Female; HeLa Cells; Humans; Hydrogen-Ion Concentration; Rats; Rats, Inbred Strains; Urinary Bladder Neoplasms; Zinostatin

Two cases of bladder carcinoma are described. The patients were of similar age, were both smokers and were treated for the same period, but exhibited completely different later clinical courses. Initially, both had a single, papillary, pedunculate tumor, identified as a transitional cell carcinoma, grade 2, pTa. One patient, six years later, had multiple papillary tumors covering almost all the mucosal surface and underwent simple cystectomy. Histologically the tumors were identified as transitional cell carcinomas, grade 2, pT1. The other patient, nine years later, had a single nodular invasive tumor with a concomitant, very tiny papillary tumor and underwent radical cystectomy. Histologically the tumor was transitional cell carcinoma, grade 2 greater than 3, pT4. Many of the questions raised by these cases are unanswered, but comparison of such cases should provide some clues to the natural history of bladder carcinoma.

Topics: Adult; Carcinoma, Transitional Cell; Cystoscopy; Humans; Male; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Smoking; Time Factors; Urinary Bladder Neoplasms; Zinostatin

We studied the effect of "two-route chemotherapy" (TRC) with intra-arterial (IA) neocarzinostatin (NCS) and IV N-(2-mercaptopropionyl)-glycine (tiopronin), its antidote, on rat limb tumors. Chemotherapy experiments were carried out on day 9 after the inoculation of 10(6) syngeneic transitional carcinoma cells into the hind limb in female Wistar King A rats. In the group given TRC, 3500 units/kg NCS and 800 mg/kg tiopronin were given via the femoral artery and the femoral vein, respectively. The antitumor effect was evaluated by the tumor weight on day 12 after the treatment. Compared with the weight of tumors in untreated controls, TRC reduced tumor weight to one-tenth, while 700 units/kg IA NCS alone reduced tumor weight to one-third and 700 units/kg systemic NCS alone reduced tumor weight to three-fourths of the control weight. In the group given TRC, WBC and nucleated bone marrow cells were completely protected and loss of body weight was slight.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Bone Marrow; Carcinoma, Transitional Cell; Female; Infusions, Intra-Arterial; Infusions, Parenteral; Leukocytes; Mice; Mice, Inbred Strains; Rats; Rats, Inbred Strains; Tiopronin; Zinostatin

Topics: Adult; Aged; Anorexia; Antibiotics, Antineoplastic; Carcinoma, Transitional Cell; Fatigue; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms; Zinostatin

Neocarzinostatin (NCZ), a new antitumor antibiotic, was administered to 19 patients with bladder cancer, 16 patients with prostatic cancer, and 3 patients with hepatoma. All patients had objectively measurable metastatic lesions including 21 with palpable nodes or subcutaneous nodules, 10 with pulmonary nodules as demonstrated by chest x-ray, 4 with malignant hepatomegaly, and 3 with bidimensional pelvic masses as demonstrated by CT scanning. Sixty-five courses of NCZ were administered via an intravenous bolus daily for five days with dosages ranging from 1500 to 3000 U/m2. Immediate toxicity was not dose-limiting except for 1 episode of anaphylaxis and 1 of acute renal failure. Myelotoxicity was delayed, dose-dependent, noncumulative, and dose-limiting. Thrombocytopenia was prolonged or irreversible in 5 cases. The maximally tolerated dose was 2750 U/m2. One patient with NCZ-associated pulmonary fibrosis and 1 with biopsy-proven hepatitis are discussed in detail. Neocarzinostatin demonstrated minimal therapeutic activity (1 partial remission) in patients with bladder cancer. There was no response in patients with prostatic cancer or hepatoma.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Carcinoma, Transitional Cell; Drug Administration Schedule; Drug Evaluation; Female; Hematoma; Humans; Leukopenia; Liver; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Respiratory Function Tests; Thrombocytopenia; Urinary Bladder Neoplasms; Zinostatin