zinostatin and Hematoma

SMANCS is the first commercially available polymer conjugated drug invented by the author, in which the protein antitumor agent neocarzinostatin is conjugated with two short chains of poly(styrene-comaleic acid) half-butylate. It exhibits the highest tumor/blood ratio (> 1,000) when injected arterially as an oily formulation in Lipiodol (SMANCS/Lipiodol). In addition, SMANCS/Lipiodol can give very high tumor contrasting image under X-ray (e.g., CT-scan), and thus the optimal dosing regimen can be determined and offers a diagnostic advantage. Phase I/II study of SMANCS was initiated in 1989 and it was approved by the Japanese Government in the fall of 1993 for the treatment of hepatoma. Exploitation of its application for other tumors such as renal cell cancer and pleural/ascitic carcinomatosis is anticipated. The response rate of Grad IV Lipiodol retention is 48.5% at 4 months; and those of 6 and 12 months are 50% and 90%, respectively. The major side effect is fever, which is only transitory, and no bone-marrow suppression, renal or hepatic toxicity were observed.

Topics: Animals; Hematoma; Humans; Infusions, Intra-Arterial; Iodized Oil; Liver; Liver Neoplasms; Maleic Anhydrides; Polystyrenes; 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