zinostatin and Lung-Neoplasms

An early phase II multicentered study of YM 881 (zinostatin stimalamer) was conducted in 36 patients to investigate response and the safety of the drug in malignant tumors. The response could be evaluated in 18 patients, one with brain tumor, 2 with lung cancer, one with breast cancer, one with liver cancer, one with pancreatic cancer, 6 with gastric cancer, and 6 with colon cancer. PR was found in the patient with brain tumor. Major subjective unwanted effects were gastrointestinal symptoms. Objective evidence of hematological changes (thrombocytopenia, decreased hematocrit, and lymphocytopenia) was also obtained.

Topics: Adult; Aged; Anorexia; Brain Neoplasms; Drug Evaluation; Female; Humans; Injections, Intravenous; Lung Neoplasms; Male; Maleic Anhydrides; Middle Aged; Neoplasms; Polystyrenes; Stomach Neoplasms; Thrombocytopenia; Vomiting; Zinostatin

Eighty-two patients with small cell lung carcinoma refractory to standard chemotherapy were entered in this phase II randomized study of PALA, amsacrine, teniposide, and zinostatin. Of the 66 evaluable patients, one partial response occurred among 17 patients treated with teniposide and no responses occurred with the other drugs. Two patients each treated with amsacrine and teniposide experienced life-threatening hematologic toxic effects and one patient treated with zinostatin died of thrombocytopenic pulmonary hemorrhage. The overall median patient survival was 9.6 weeks. Weight loss greater than or equal to 5% prior to therapy, extensive disease, and a nonambulatory status were associated with poor survival.

Topics: Aminoacridines; Amsacrine; Antibiotics, Antineoplastic; Antineoplastic Agents; Aspartic Acid; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Drug Evaluation; Humans; Lung Neoplasms; Phosphonoacetic Acid; Random Allocation; Teniposide; Zinostatin

Eighty-nine patients with advanced non-small cell bronchogenic carcinoma were treated with either m-AMSA 120 mg/m2 intravenously every 3 weeks or neocarzinostatin 2.0 mg/m2 intravenously daily X 5 every 4 weeks. There were no responses in 40 evaluable patients who received m-AMSA and three partial responses (7.5%) in 40 patients who received neocarzinostatin. Two patients receiving m-AMSA had drug-related deaths. For m-AMSA the major toxicities were hematologic, while for neocarzinostatin the major toxicities were hematologic, gastrointestinal, and fever. We conclude that m-AMSA is inactive while neocarzinostatin has minimal activity in non-small cell bronchogenic carcinoma.

Topics: Aged; Aminoacridines; Amsacrine; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Drug Administration Schedule; Drug Evaluation; Humans; Lung Neoplasms; Random Allocation; Zinostatin

The patient was a 61-year-old female with alcoholic liver cirrhosis, who was admitted to our hospital due to elevation of AFP.During the evaluation, both abdominal ultrasound and enhanced abdominal CT revealed a hepatocellular carcinoma measuring 4 cm in the S6-7 region, complicated with an arteriovenous shunt.Additionally, the lung CT examination showed 20 isolated bilateral lung tumors, all of which were less than 1.4 cm in diameter. Following the diagnosis, we performed a transcatheter arterial infusion chemotherapy of SMANCS at 3 mg through the right heptic artery. Thereafter, the AFP level returned to normal. Additionally, the tumors previously observed in both liver and lung, and exhibited by both lung CT and enhanced abdominal MRI, had disappeared.The patient has been in clinical remission more than 10 years to date.

Topics: Carcinoma, Hepatocellular; Disease-Free Survival; Female; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Maleic Anhydrides; Middle Aged; Polystyrenes; Time Factors; Tomography, X-Ray Computed; Zinostatin

A case of hepatocellular carcinoma, successfully treated with multimodal loco-regional treatments, is reported. An 80-year-old male presented with multiple pulmonary and peritoneal metastases 4 months after right heimihepatectomy for ruptured HCC. Bronchial artery infusion of mitomycin C induced pulmonary tumor regression and stabilization. Peritoneal tumor was treated by arterial infusion of SMANCS, followed by percutaneous injection of absolute ethanol, which ended in surgical removal in 28-postoperative month due to abscess formation. He had been well until right adrenal and left pulmonary metastases appeared. Resection of both metastases was carried out in 39-post hepatectomy month. Recurrent left pulmonary metastasis was treated with two sessions of bronchial artery infusion with no effect this time. Video-assisted partial resection of the left lung was performed in 54 post-hepatectomy month. But his AFP level kept rising. Eventually pulmonary metastasis recurred and tumor thrombus reached the left atrium 58 months after hepatectomy. He wanted no more treatment. He died of cerebral infarction caused by tumor thrombus. He enjoyed a good QOL for five years through multimodal loco-regional treatments.

Topics: Aged, 80 and over; Antineoplastic Agents; Bronchial Arteries; Carcinoma, Hepatocellular; Ethanol; Hepatectomy; Humans; Infusions, Intra-Arterial; Injections, Intralesional; Liver Neoplasms; Lung Neoplasms; Male; Maleic Anhydrides; Mitomycin; Peritoneal Neoplasms; Polystyrenes; Zinostatin

To clarify the effect of SMANCS on malignant pleural carcinomatosis, seven patients with malignant pleural effusion were treated with SMANCS administered via an intracavitary route. Five patients showed improvement after one or two injections of SMANCS into the thoracic cavity, although 2 patients needed further therapy with the immunopotentiating agent picibanil (OK-432). No serious adverse effects were observed. This simple therapeutic tactic with SMANCS may be effective in cases of malignant pleural carcinomatosis.

Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Colonic Neoplasms; Female; Humans; Lung Neoplasms; Male; Maleic Anhydrides; Middle Aged; Pleural Effusion, Malignant; Polystyrenes; Stomach Neoplasms; Zinostatin

Monoclonal antibody-drug conjugate, A7-NCS, was applied for 73 patients with colorectal and pancreatic cancer, including metastasis of liver, lung and peritoneum. Monoclonal antibody A7, from a mouse splenocyte immunized against human colon cancer was bound covalently to Neocarzinostatin (NCS), Mitomycin C (MMC) and Adriamycin (ADM) to form A7-NCS, A7-MMC and A7-ADM, respectively. Fifty-four patients with colon cancer, fifteen patients with postoperative liver metastasis of colorectal cancer and one patient with advanced pancreatic cancer were given A7-NCS intra-arterially. Two patients with postoperative lung metastasis of colon cancer were injected intra-venously and one patient with postoperative peritoneal metastasis of colon cancer was given it intraperitoneally. Three patients with liver metastasis showed evidence of tumor reduction on CT scan and three claimed pain relief. Postoperative survival of the patients with distant metastasis exhibited slightly higher survival rate in the patients with A7-NCS, as compared with the patients without A7-NCS. There was no serious adverse effect in the patients given A7-NCS. Human anti-mouse antibody (HAMA) was detected in all patients given the conjugate. Repeated injections of A7-NCS for several consecutive days following the first injection brought about the same A7 pattern as the first injection.

Topics: Aged; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Colorectal Neoplasms; Doxorubicin; Drug Administration Schedule; Female; Humans; Immunotoxins; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Pancreatic Neoplasms; Prognosis; Survival Rate; Zinostatin

The oily anticancer agents dissolved in lipiodol used for arterial administration against various solid tumors in our department were found to be applicable to treat for pleural or peritoneal carcinomatosis experimentally and clinically. The pharmacokinetic study with rat model showed oily anticancer agents were retained in a high concentration in the peritoneal cavity compared to water-soluble anticancer agents. In our pilot clinical study all patients with pleural or peritoneal carcinomatosis showed improvement cytologically and physically.

Topics: Adult; Aged; Animals; Antibiotics, Antineoplastic; Ascitic Fluid; Carcinoma, Hepatocellular; Doxorubicin; Female; Furans; Humans; Infusions, Parenteral; Iodized Oil; Liver Neoplasms; Liver Neoplasms, Experimental; Lung Neoplasms; Male; Maleic Anhydrides; Middle Aged; Pleural Effusion; Polystyrenes; Rats; Rats, Inbred Strains; Zinostatin

Transcatheter arterial chemotherapy (SMANCS/lipiodol) was applied to massive hepatoma, which had a high AFP 213,000 ng/ml, A-P shunt, tumor thrombosis and metastatic lung cancer. After 3 months, the AFP value reduced to 18 ng/ml, massive hepatoma and the A-P shunt disappeared, but AFP-negative nodular hepatoma recurred around initial hepatoma. Each time, we injected SMANCS/lipiodol to the recurring hepatoma. The therapy in the initial stage was not so effective. The portal vein was not observed in the initial stage, but appeared after the second dosage. Metastatic lung cancer was declining in the initial dosage and 23 months later disappeared after the third dosage. The massive hepatoma occupied entirely the rt. lobe of the liver. The patient lived for 4 years, had total admission periods of 190 days and could return to life in society. In this case, we considered that transcatheter arterial chemotherapy (SMANCS/lipiodol) had remarkable effects.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Hepatocellular; Follow-Up Studies; Furans; Humans; Infusions, Intra-Arterial; Iodized Oil; Liver Neoplasms; Lung Neoplasms; Male; Maleic Anhydrides; Middle Aged; Polystyrenes; Prognosis; Remission Induction; Zinostatin

Fifteen patients with advanced renal cell carcinoma underwent chemotherapy of neocarzinostatin (NCS). First, 6-8 mg of NCS was infused into renal artery at angiography; second, 6-8 mg was infused by the same route just before ligation of renal artery at nephrectomy, if possible; and third, 2 mg was given intravenously at 2-week intervals, about 10 times. One patient who suffered from metastatic renal cancer on rs. tibia was treated by femoral arterial injection of 2 mg NCS 5 times. By treatment of NCS for advanced renal cell carcinoma 2 out of fifteen patients achieved complete regression, one patient showed partial regression and four a minor response. Effective rate (CR + PR) of NCS for metastatic renal cancer was 20%, and the response rate (CR + PR + MR) was 47%. We consider that NCS is presently the most effective drug for renal cell carcinoma.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Carcinoma, Renal Cell; Combined Modality Therapy; Female; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Kidney Neoplasms; Lung Neoplasms; Male; Middle Aged; Nephrectomy; Zinostatin

Cellular glutathione (GSH) levels were found to be 7-fold higher in a human lung adenocarcinoma cell line (A549) than in a normal human lung fibroblast line (CCL-210). Differential modulation of cellular GSH was explored in these cell lines by (a) stimulation of GSH synthesis by oxothiazolidine-4-carboxylate (OTZ) and (b) inhibition of GSH synthesis by buthionine sulfoximine (BSO). In the tumor cell line, OTZ treatment had no effect; however, GSH levels of 140-170% of control were achieved in the normal fibroblast line. With BSO, the normal cell line was depleted of GSH at a faster relative rate than with the tumor line. Within 7 h, 5% GSH remained in the CCL-210 line while approximately 40% GSH remained in the A549 line. Survival response of normal versus tumor cell lines to selected chemotherapy drugs was compared following modulation of GSH levels. OTZ pretreatment of the A549 line provided no protection to a 1-h exposure to melphalan, cisplatin, or bleomycin; however, OTZ pretreatment of CCL-210 elevated GSH and provided protection to melphalan, cisplatin, and bleomycin (protection ratios at 5% survival of 1.2, 1.4, and 1.4, respectively). Neocarzinostatin toxicity in the normal CCL-210 line pretreated with BSO was greatly reduced (protection ratio at 50% survival = 5.0). The same BSO treatment to A549 cells (40% GSH remaining) yielded a similar survival curve to control cells. These studies demonstrate that selective differential chemotherapy responses of normal versus tumor cells is possible by manipulating the GSH synthetic cycle. Should basic phenotypic differences with regard to reductive capacity exist in vivo, such manipulation in GSH levels might yield a therapeutic gain for carefully selected chemotherapy drugs.

Topics: Antineoplastic Agents; Bleomycin; Buthionine Sulfoximine; Cell Survival; Cells, Cultured; Cisplatin; Glutathione; Humans; Lung; Lung Neoplasms; Melphalan; Methionine Sulfoximine; Neoplasms; Pyrrolidonecarboxylic Acid; Thiazoles; Thiazolidines; Zinostatin

Theoretical considerations for tumor-selective chemotherapy are described which based on the unique character of the tumor neovasculature. Namely, most solid tumors possess four different unique features: hypervasculature, enhanced permeability even to macromolecules, architectural differences, and lack of the lymphatic recovery system. Lipid or lipid contrast medium and macromolecular anticancer agents using prototype drug smancs can be utilized for cancer-selective targeting based on the above four features. Selective targeting with lipid contrast medium with smancs has offered two clinical benefits; definite and pronounced antitumor effect and diagnostic value. These effects can be primarily attributed to the tumor-selective accumulation of the agent, i.e., more than 1,000 times greater in the tumor than in the plasma. As a consequence very few side effects are observed clinically. Primary or secondary hepatoma and lung cancer showed size reduction in more than 90 % of treated patients. Very few side effects such as hematosuppression or inhibited liver function were observed in these cases. Prolongation of life-span was marked in the patients. The above results indicate a new future direction for the development of the tumor-selective chemotherapy.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Biological Availability; Capillary Permeability; Furans; Iodized Oil; Liver Neoplasms; Lung Neoplasms; Macromolecular Substances; Maleic Anhydrides; Mitomycin; Mitomycins; Neoplasms; Neoplasms, Experimental; Polystyrenes; Rabbits; Zinostatin

We report a case of histologically confirmed pulmonary and hilar metastases from renal cell carcinoma. Complete response to neocarzinostatin has been maintained for 18 months.

Topics: Aged; Antibiotics, Antineoplastic; Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Lung Neoplasms; Male; Radiography; Zinostatin

Topics: Aged; Antibiotics, Antineoplastic; Ethiodized Oil; Female; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Lung Neoplasms; Male; Maleic Anhydrides; Middle Aged; Molecular Weight; Polystyrenes; Zinostatin