zinostatin and Kidney-Neoplasms

Renal cancer is a typical tumor most insensitive to standard chemotherapy, but this hypervascular tumor has an anatomical feature by which its main feeding artery is readily accessible to transarterial targeting treatments. Effects of arterial chemoembolization, a prototype targeting chemotherapy, on renal cancer were reviewed.

Topics: Brachytherapy; Carcinoma, Renal Cell; Chemoembolization, Therapeutic; Humans; Kidney Neoplasms; Maleic Anhydrides; Mitomycin; Polystyrenes; Survival Rate; Zinostatin

The treatment for metastatic renal cell carcinoma (RCC) has changed dramatically after the beginning of molecular-targeted therapies. However,the treatment for liver metastasis is still difficult in patients with metastatic RCC. We treated liver metastases (8 target lesions) of RCC with stylene-maleic acid neocarzinostatin (SMANCS)/Lipiodol therapy. At the treatment procedure,a catheter was inserted at the femoral artery (Seldinger's method),a microcatheter was selectively inserted into the branch of hepatic artery which fed the liver metastasis,and then SMANCS/Lipodol was infused. We treated 1,2 and 1 patient 4,2, and 1 time,respectively. One lesion treated with SMANCS/Lipodol was further treated by radiofrequency ablation 13 days later. Of 6 metastatic lesions which could be followed up for more than 6 months after the treatment,one had partial response for 4 months and 4 had stable disease for more than 6 months. Four of the 6 lesions shrunk after SMANCS/Lipiodol treatment. Two of 4 patients survived more than 18 months after the first SMANCS/Lipiodol therapy. In all 9 SMANCS/Lipiodol treatments,grade 1 liver dysfunction (44.4%),ascites (11.1%) and fatigue (11.1%) occurred after the treatments. These adverse events were all improved by conservative treatments. SMANCS/Lipiodol therapy can be a treatment option as local treatment for liver metastasis of RCC.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Renal Cell; Ethiodized Oil; Female; Humans; Infusions, Intra-Arterial; Kidney Neoplasms; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Polystyrenes; Zinostatin

The purpose of this study is to evaluate the improved method of arterial infusion therapy of SMANCS (SX) with lipiodol under the angiotensin-induced hypertensive state for various difficult-to-treat solid tumors. Most patients were unresectable with no other therapeutic options, recurrence after resection, or patients do not respond to common treatments. The new method utilizes angiotensin II (AT) to induce hypertension (e.g. approximately 15-30 mmHg above norm) for 15-20 min. This method was successfully applied to metastatic liver cancer, cholangiocarcinoma, massive renal cell carcinoma, pancreatic and other abdominal solid cancers. This AT-induced hypertension resulted in remarkably enhanced tumor delivery accompanied by improved therapeutic response, and a shorter time to achieve 50% regression of tumor size with least toxicity. We demonstrated clinically herein improved therapy for various advanced solid tumors with SX by elevating the tumor blood flow selectively. This is the first clinical proof that modulations of vascular pathophysiology can uniquely accomplish enhanced tumor selective delivery of polymeric drugs and thus yielded better clinical outcome.

Topics: Adenocarcinoma; Adult; Aged; Angiotensin II; Antineoplastic Agents; Blood Pressure; Carcinoma, Renal Cell; Cholangiocarcinoma; Drug Delivery Systems; Female; Humans; Hypertension; Infusions, Intravenous; Japan; Kidney Neoplasms; Liver Neoplasms; Male; Maleic Anhydrides; Middle Aged; Neoplasm Staging; Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms; Polystyrenes; Vasoconstrictor Agents; Zinostatin

To evaluate the anticancer effects of a lipophilic macromolecular anticancer agent, poly(styrene-co-maleic acid)-conjugated neocarzinostatin (SMANCS), dissolved in a lipid contrast medium (Lipiodol) given via the renal artery to patients with renal cell carcinoma.. Among 467 patients with renal cell carcinoma treated between April 1984 and March 1993, 191 were treated with SMANCS dissolved in a lipid contrast medium (a 3:2 mixture of Lipiodol F and Lipiodol Ultrafluid; Lpd). Selective arterial infusion of SMANCS/Lpd was performed at a dose of 1.0 or 1. 5 mg/mL. The infusion was repeated at intervals of about 2 weeks or longer, but the doses and the total number of infusions varied among patients, according to results of computed tomography analysis.. Statistical analysis was performed for 415 patients who met the criteria of this study. Twenty-six surgical patients with metastases who underwent infusion therapy of SMANCS/Lpd for primary lesions showed 3 and 5-year survival rates of 23.0% and 12.8%, respectively; the rates were 19.3% and 9.7% in 31 patients who did not receive SMANCS infusion therapy. In 125 surgical patients without metastases who underwent SMANCS/Lpd infusion, the 5 and 10-year survival rates were 83.0% and 75.2%, respectively, whereas rates of 84.6% and 78.9% were observed in 199 surgical patients whose median tumor size was significantly smaller, however, than the SMANCS/Lpd infusion group. The maximal tumor diameter at the beginning of treatment was significantly larger (mean diameter 70.8 mm) in the SMANCS/Lpd infusion group than in the noninfusion group (59.1 mm). The survival rate was statistically better for patients with tumors of 100 mm diameter or larger in the SMANCS/Lpd infusion group (P <0.05): 5 and 10-year survival rates were 70.4% and 61.6%, respectively, for the infusion group and 64.6% and 50.9% for the group receiving no drug. In patients with larger tumor (greater than 110 mm), the survival rate at 13 years was 75% in the SMANCS/Lpd infusion group and 0% in the surgery group.. Arterial infusion therapy with SMANCS/Lpd appears to be effective for large renal cell carcinoma without metastases in conjunction with surgery.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Renal Cell; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infusions, Intra-Arterial; Iodized Oil; Kidney Neoplasms; Male; Maleic Anhydrides; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Polystyrenes; Survival Rate; Tomography, X-Ray Computed; Treatment Outcome; Zinostatin

Twenty-five patients with renal cell carcinoma were treated with a lipophilic macromolecular drug, poly(stylene-co-maleic acid)-conjugated neocarzinostatin (SMANCS) dissolved in lipid contrast medium (Lipiodol). The drug was injected by catheterizing the renal artery and another feeding artery in 24 patients, and in the common hepatic artery in 1 patient with metastases to the liver after a radical nephrectomy. The procedure of selective arterial administration of 3-20 mg/mL of SMANCS/Lipiodol was simple to perform and was required once every two to three weeks. Total dose of SMANCS for each patient varied from 3 to 57 mg. Both SMANCS and Lipiodol accumulated more selectively in tumor than in any other tissue and remained in the neovasculature and extracapillary space for a long time. CT pattern of the remaining oil contrast medium in the tumor was characterized by the high-density area localized mainly in the periphery of the tumor around the central necrosis. When hyperviscosity Lipiodol (Lipiodol HV) was used as lipid contrast medium, it remained more persistently in the tumor and disappeared more slowly than Lipiodol. Moreover, the pronounced anticancer effect was recognized when SMANCS/Lipiodol HV was administered compared with only SMANCS/Lipiodol. Severe side effects, such as myelosuppression, unendurable pain, paralytic ileus, etc., were not observed. This targeting chemotherapy may be of great significance for advanced renal cell carcinoma.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Renal Cell; Female; Humans; Infusions, Intra-Arterial; Iodized Oil; Kidney Neoplasms; Male; Maleic Anhydrides; Middle Aged; Polystyrenes; Zinostatin

Eighteen patients with stages I to III renal cell carcinoma were treated with Neocarzinostatin before, during and after nephrectomy. The mean cumulative dose of Neocarzinostatin was 18.0 mg. With a minimum follow-up period of 57 months (4.8 years), two of 18 patients developed metastasis and both were dead. Of 17 control patients who were observed for 72 months (6.0 years) or more, ten had recurrent disease and eight of them were dead. The 5-year survival rates were 94% for patients who received Neocarzinostatin and 62% for control patients. There was a statistical difference in survival between these two groups. Neocarzinostatin seems to be effective in the prevention of postoperative recurrence of renal cell carcinoma.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Carcinoma, Renal Cell; Combined Modality Therapy; Drug Evaluation; Female; Humans; Intraoperative Care; Kidney Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Nephrectomy; Postoperative Care; Preoperative Care; Recurrence; 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

Topics: Adult; Aged; Antibiotics, Antineoplastic; Carcinoma, Renal Cell; Embolization, Therapeutic; Female; Furans; Humans; Iodized Oil; Kidney Neoplasms; Male; Maleic Anhydrides; Middle Aged; Polystyrenes; 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: Antibiotics, Antineoplastic; Child; Female; Furans; Humans; Infusions, Intra-Arterial; Iodized Oil; Kidney Neoplasms; Male; Maleic Anhydrides; Middle Aged; Mitomycin; Mitomycins; Polystyrenes; Renal Artery; Zinostatin