aclarubicin and Urinary-Bladder-Neoplasms

The present investigation was conducted to examine the effect of neoadjuvant PVB and CAP regimens for locally invasive bladder cancer and consisted of two studies: (1) a retrospective nonrandomized study of neoadjuvant PVB therapy, and (2) a well-controlled randomized study of neoadjuvant CAP therapy. A total of 25 patients with primary locally invasive bladder cancer were entered into the PVB study between January 1981 and December 1985. Since 1986, 31 patients have been randomized into the CAP study. In the PVB-treated group, a 71.4% complete response (CR) plus partial response (PR) rate and a 71.4% downstaging were noted. On the other hand, in the CAP-treated group, a 50.0% CR plus PR rate and a 88.9% downstaging were noted. The 2- and 5-year survival rates of neoadjuvant PVB were 78.6 and 60.6%, respectively. In contrast, the 2-year survival rate of the neoadjuvant CAP-treated group was 100% at a mean follow-up of 15.8 months. No statistical significance was achieved in the survival rates. These results indicated that neoadjuvant PVB and CAP would be useful in the management of invasive bladder cancer.

Topics: Aclarubicin; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Transitional Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Neoplasm Invasiveness; Peplomycin; Randomized Controlled Trials as Topic; Retrospective Studies; Survival Analysis; Urinary Bladder Neoplasms; Vinblastine

F 11782 (2",3"-bis pentafluorophenoxyacetyl-4",6"-ethylidene-beta-D-glucoside of 4'-phosphate-4'-dimethylepipodophyllotoxin, di-N-methyl glucamine salt) is a newly synthesized dual catalytic inhibitor of topoisomerases I and II with major in vivo antitumour activity. In this study, we compared and contrasted F 11782 with three other known inhibitors of both these nuclear enzymes, namely aclarubicin. intoplicin and TAS-103, and established its novel mechanism of action.. In vitro growth-inhibitory effects against a panel of murine and tumour cell lines were measured by cell counting, clonogenicity or tetrazolium metabolic dye (MTT) assays. In vivo antitumour activities were evaluated against two murine tumour models (i.v. P388 leukaemia and s.c. B16 melanoma). Finally, interactions with either DNA or DNA-topoisomerases were determined using various methodologies: DNA-intercalator displacement, pBR322 DNA relaxation, kDNA decatenation, topoisomerase II extractability measurements, stabilization of topoisomerase-induced cleavable complexes (CC) in vitro and in cells, and gel retardation assays.. F 11782 had a different profile of sensitivities and proved generally less cytotoxic than the other dual inhibitors tested in vitro, while showing significantly superior antitumour activity in vivo. F 11782, which did not stabilize CC either in vitro or in cells, was the only compound of this series capable of inhibiting the catalytic activity of both DNA-topoisomerases without interacting with DNA, and of completely impairing the binding of these nuclear proteins to DNA. Moreover, only cotreatment of cells in vitro with F 11782 enhanced the cytotoxic activity of etoposide.. These results emphasize the novel mechanism of action of F 11782 vis-a-vis the other dual inhibitors of topoisomerases I and II and so augur well for its future clinical development.

Topics: Aclarubicin; Aminoquinolines; Animals; Antineoplastic Agents; Cell Division; Enzyme Inhibitors; Etoposide; Humans; Indenes; Indoles; Leukemia L1210; Leukemia P388; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Naphthalenes; Pyrans; Pyridines; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors; Tumor Cells, Cultured; Urinary Bladder Neoplasms

Ten patients with advanced bladder cancer were treated with intra-arterial infusion therapy. The patients consisted of nine males and one female between 55 and 82 years old (median: 70 years). In all patients, cisplatinum (CDDP) (2 mg/kg), aclacinomycin (ACR) (0.5 mg/kg) and Angiotensin II (25 mg) were infused via the internal iliac artery for a period of about 30 minutes. Seven patients also received X-ray therapy with a linac. The efficacy of this therapy was assessed by computed tomographic scanning, sonography and cystoscopy. As a result of this assessment, 2 patients were rated complete response "(CR)", 6 partial response (PR) (showing 50% or more reduction in the lesion) and 2 no change "(NC)". To compare the efficacy of this therapy for two histopathologically defined groups of patients (patients with grades 2 and 3 cancer), one patient was rated "CR", four "PR" and two "NC" in the grade 3 group (total 7 patients), while one was rated "CR" and two "PR", in the grade 2 group (total 3 patients). In effective cases, pollakiuria and miction pain disappeared shortly following intra-arterial infusion therapy. As for side effects of the therapy, mild nausea or vomiting was observed in all patients, while leukopenia was noted in one patient.

Topics: Aclarubicin; Aged; Aged, 80 and over; Angiotensin II; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Naphthacenes; Remission Induction; Urinary Bladder Neoplasms

Thirteen patients with recurrent superficial bladder tumors were treated by combined intravesical instillation of Aclacinomycin-A (ACM) and cytosine arabinoside (CA). Prophylactic effects of this combined instillation therapy were studied in 7 patients. A solution of 200 micrograms/ml of ACM and 600 micrograms/ml of CA was instilled into the bladder. The instillation aimed for treatment was carried out once a week until ten treatments had been given. Complete response was attained in 2 patients and partial response in 3 patients, but tumor size increased by more than 50% in 6 of the 13 patients. No change was observed in the remaining 2 patients. Recurrence of the tumors was observed in 3 of the 7 patients who were treated by this prophylactic combined instillation therapy. Local side effects such as bladder irritability were found in 2 of the 20 patients. No systemic side effects were noted in any patients. Although the side effects were reduced, we were not satisfied with the results of this therapy.

Topics: Aclarubicin; Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cytarabine; Drug Evaluation; Female; Humans; Male; Middle Aged; Naphthacenes; Neoplasm Recurrence, Local; Remission Induction; Urinary Bladder Neoplasms

In vitro and in vivo effects of mitoxantrone, aclacinomycin-A and doxorubicin were examined in a transplantable murine transitional bladder carcinoma, FCB. The in vitro parameters used included monolayer growth kinetics, tumor stem-cell colony formation and autoradiographic analysis of thymidine labeling. Monolayer growth kinetics revealed that both mitoxantrone and aclacinomycin-A resulted in reductions in FCB cell growth, which were significantly higher (41% and 65%, respectively) than those seen with doxorubicin treatment (22%). Similarly, by the stem-cell assay, an increased reduction in colony formation was seen in aclacinomycin-A (98%) and mitoxantrone (91%) treated cultures when compared with doxorubicin (51%) treated cultures. Autoradiographic data revealed that 24-h exposure with both aclacinomycin-A and mitoxantrone significantly inhibited thymidine incorporation (98% and 80% respectively), which was an increase over doxorubicin (19%). In vivo studies revealed that aclacinomycin-A treatment increased the mean life span of C57BL mice by 60.6% when compared with a 33.6% increase in doxorubicin-treated animals and a 19.7% increase in mitoxantrone-treated animals. Both the in vitro and in vivo data suggest that aclacinomycin-A is a superior drug when used against this specific murine bladder tumor cell and that further testing of this agent for its efficacy in other urologic tumors is justified.

Topics: Aclarubicin; Animals; Carcinoma, Transitional Cell; Cell Division; Cell Line; Dose-Response Relationship, Drug; Doxorubicin; In Vitro Techniques; Mice; Mice, Inbred C57BL; Mitoxantrone; Naphthacenes; Time Factors; Tumor Stem Cell Assay; Urinary Bladder Neoplasms

Nine patients with progressive urothelial tumors treated with combination chemotherapy were evaluated. The median age of the patients was fifty-four; 6 men and 3 women; 7 of the tumors were of the renal pelvis and/or ureter and at stage C or D at the time of initial chemotherapy. Another of the tumors was triple cancer (bladder, prostate, sigmoid) and the remaining case was of bladder cancer. The stage of the two bladders cancers was T4. All patients were treated with CDDP (cis-platinum), ACR (aclarubicin hydrochloride) and HCFU (carmoful) and given from one to 3 courses repeated at three-week intervals (mean 2.3 courses). Seven patients were evaluable while two had no evaluable lesions. The response with this chemotherapy was 2 cases of PR (28.5%), 4 cases of NC and one case of PD. No severe toxicities such as nephrotoxicity or cardiotoxicity, were revealed with this combination chemotherapy.

Topics: Aclarubicin; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Humans; Kidney Neoplasms; Kidney Pelvis; Male; Middle Aged; Naphthacenes; Ureteral Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms

Topics: Aclarubicin; Antineoplastic Agents; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Colony-Forming Units Assay; Doxorubicin; Drug Evaluation, Preclinical; Humans; Kidney Neoplasms; Kidney Pelvis; Naphthacenes; Tumor Stem Cell Assay; Urinary Bladder Neoplasms; Vinblastine

Thirty-nine patients with superficial bladder cancer underwent intravesical instillation therapy of Aclacinomycin-A (ACM). Antitumor effect of ACM was evaluated in 19 patients and objective responses (CR + PR) of tumor were observed in 84.2% of these patients. Prophylactic instillation therapy of ACM was carried out on 20 patients and the results were compared with those obtained for 10 control patients who had first episode of bladder tumor and received no instillation therapy. No significant difference in the recurrent rate was observed between these two groups. The major side effect for instillation therapy with ACM was bladder irritation which appeared in 38.5% of all the patients.

Topics: Aclarubicin; Adult; Aged; Antibiotics, Antineoplastic; Drug Administration Schedule; Drug Evaluation; Humans; Injections; Middle Aged; Naphthacenes; Neoplasm Recurrence, Local; Urinary Bladder; Urinary Bladder Neoplasms