aclarubicin and Carcinoma--Squamous-Cell

Topics: Aclarubicin; Adenocarcinoma; Adult; Aged; Antibiotics, Antineoplastic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Lung Neoplasms; Male; Middle Aged; Naphthacenes

Topics: Aclarubicin; Adult; Aged; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Clinical Trials as Topic; Drug Evaluation; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Naphthacenes; Research Design

In the course of screening for an inhibitor of farnesyl transferase (FTase), we identified two compounds, N-benzyl-aclacinomycin A (ACM) and N-allyl-ACM, which are new derivatives of ACM. N-benzyl-ACM and N-allyl-ACM inhibited FTase activity with IC50 values of 0.86 and 2.93 μM, respectively. Not only ACM but also C-10 epimers of each ACM derivative failed to inhibit FTase. The inhibition of FTase by N-benzyl-ACM and N-allyl-ACM seems to be specific, because these two compounds did not inhibit geranylgeranyltransferase or geranylgeranyl pyrophosphate (GGPP) synthase up to 100 μM. In cultured A431 cells, N-benzyl-ACM and N-allyl-ACM also blocked both the membrane localization of H-Ras and activation of the H-Ras-dependent PI3K/Akt pathway. In addition, they inhibited epidermal growth factor (EGF)-induced migration of A431 cells. Thus, N-benzyl-ACM and N-allyl-ACM inhibited EGF-induced migration of A431 cells by inhibiting the farnesylation of H-Ras and subsequent H-Ras-dependent activation of the PI3K/Akt pathway.

Topics: Aclarubicin; Alkyl and Aryl Transferases; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Membrane; Cell Movement; Epidermal Growth Factor; Farnesyltranstransferase; Genes, ras; Geranylgeranyl-Diphosphate Geranylgeranyltransferase; Humans; Inhibitory Concentration 50; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt

We examined the effectiveness of 5 anticancer agents in nude mice transplanted with 4 kinds of uterine cervical adenocarcinoma. MMC, CDDP, ACM, ACD and VP-16 were selected. The therapeutic effects were assessed in terms of growth inhibition rates and histological effects in the transplanted tumors of nude mice. From this study, the following results were obtained: In single agent administration, MMC was effective in all tumors, and CDDP was effective in 3 kinds of tumors as indicated by the results showing growth inhibition rates. Histological findings for the agents did not correlate with therapeutic findings. In combined administration, MMC + CDDP was the most effective as indicated by the results showing growth inhibition rates; this combination showed an additive effect and MMC and CDDP were considered to be key drugs for treating cervical adenocarcinoma. On the basis of these results, we used combination chemotherapy with MMC, CDDP and ACM (PAM regimen) in high risk and advanced patients. We found an improved prognosis in advanced patients. There were one complete response and three partial responses in 7 advanced cases including one suffering recurrence. The combination therapy including MMC, CDDP and ACM was found to be effective against cervical adenocarcinoma.

Topics: Aclarubicin; Adenocarcinoma; Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Dactinomycin; Drug Administration Schedule; Etoposide; Female; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Mitomycin; Neoplasm Transplantation; Uterine Cervical Neoplasms

Ten patients with progressive cervical carcinoma were treated with intra-arterial infusion by BOAI (balloon occluded arterial infusion) in order to secure high concentrations of anti-tumor agents. This study included 9 cases (2 stage IIb, 5 stage IIIb, and 2 stage IV) with squamous cell carcinoma and 1 case (stage IIIb) with adenocarcinoma. Cis-platin (CCDP) 100 mg/body and bleomycin (BLM) 20-30 mg/body and and/or aclacinomycin (ACM) 30-40 mg/body were infused after the bilateral internal iliac arteries were occluded. 1. The serum concentration of free-Pt reached its maximum 15-30 min after BOAI therapy and returned to an undetectable level in 3 hours. 2. The free-Pt concentration following BOAI therapy was 2 to 3 times greater than those found with intravenous infusion. 3. The free-Pt concentration in internal iliac arteries was twice as great as those observed in the femoral arteries or peripheral veins. 4. The tissue concentration of Pt after BOAI was significantly (p less than 0.05) greater than those found with intra-venous infusion. 5. BOAI treatment resulted in 2 cases of partial response, 6 cases of minor response and 2 cases with no change. These results demonstrate that BOAI therapy is effective for the treatment of progressive cervical carcinoma by increasing intratumoral concentrations of the drugs.

Topics: Aclarubicin; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Catheterization; Cisplatin; Embolization, Therapeutic; Evaluation Studies as Topic; Female; Humans; Iliac Artery; Infusions, Intra-Arterial; Infusions, Intravenous; Infusions, Parenteral; Middle Aged; Platinum; Remission Induction; Tissue Distribution; Uterine Cervical Neoplasms

Topics: Aclarubicin; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bronchoalveolar Lavage Fluid; Bronchopneumonia; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Doxorubicin; Humans; Lung; Lung Neoplasms; Male; Methotrexate; Middle Aged; Peplomycin; Vincristine

Topics: Aclarubicin; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Disseminated Intravascular Coagulation; Humans; Lung; Lung Neoplasms; Male; Necrosis; Radiography; Respiratory Distress Syndrome

Thirteen patients with metastatic brain tumors were treated with two different chemotherapy regimens. Six patients were treated with three antitumor drugs, UFT, CDDP and ACR (Group A) and the other seven patients were treated with two antitumor drugs, CDDP and ACR (Group B). Initial response to each therapy was compared with the changes in tumor size on CT scan and clinical state before and after treatment. Five cases in Group A demonstrated complete remission and one case revealed partial response on CT scan. The residual tumor on CT scan at one month in one case of partial response also completely disappeared after three months. It was thought that there might have been an effect of UFT in this case. Four cases in Group B showed complete remission and three cases revealed partial response on CT scan. However, the CT findings in the three cases of partial response were unchanged on follow-up CT scan. Clinical state evaluated by Karnofsky scale did not deteriorate in Group A, while three cases showed a deteriorated Karnofsky scale in Group B. As side effects, there were mild myelosuppression, nausea and vomiting in both Groups, which did not persist for a long time. The cause of death in both Groups was mainly recurrence of the primary lesion or metastasis to other organs. It was thought that the effect in Group A was better than that in Group B as a result of these findings. The tissue concentration of ACR was measured in six patients, and the mean value was 0.558 micrograms/g at 15 min. This concentration was thought high enough to kill tumor cells.

Topics: Aclarubicin; Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain; Brain Neoplasms; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Naphthacenes; Tegafur; Tomography, X-Ray Computed; Uracil

Aclacinomycin A (ACLA-A) was administered to 22 patients with metastatic measurable bronchogenic squamous-cell carcinoma in a Phase II trial of the drug. Sixteen patients were fully assessable for response and toxicity. The initial dose of ACLA-A was 85 mg/m2 weekly for 4 consecutive weeks; however, due to severe myelosuppression, the weekly dose was reduced to 65 mg/m2. Fifteen patients were previously untreated. Toxicity was primarily hematological. Complete or partial responses were not observed on this treatment schedule. ACLA-A administered on this schedule lacks therapeutic efficacy in the treatment of patients with advanced bronchogenic squamous-cell carcinoma.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Carcinoma, Bronchogenic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Evaluation; Humans; Infusions, Intravenous; Lung Neoplasms; Middle Aged; Naphthacenes; Time Factors

Sixteen patients with advanced squamous cell carcinoma of the head and neck were entered into a phase II trial of Aclacinomycin-A (ACM), 100 mg/M2 administered by brief infusion every three weeks. All patients had received prior radiation therapy and prior non-anthracycline containing chemotherapy. No clinically significant disease regression was observed in fourteen patients having adequate trials. The major toxicity was myelosuppression; leukopenia occurred in 93% of patients. Gastro-intestinal toxicity was mild and included two patients with transient liver function test abnormalities. No antitumor activity was observed in this patient population which was heavily pre-treated and had a median Karnofsky performance status of only 60%. The results of other phase II trials of ACM-A have been similarly disappointing suggesting that it is not a clinically useful agent in the treatment of solid tumors.

Topics: Aclarubicin; Adult; Aged; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Drug Evaluation; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Naphthacenes

Aclacinomycin-A was evaluated in a phase II trial for advanced head and neck cancer. A weekly infusion of 65 mg/m2 was used. Eighteen patients were entered. Fifteen patients were evaluable for response and toxicity. One was evaluable for toxicity only and two died before completion of a full course of therapy. One patient without previous chemotherapy achieved a PR in a neck node for a short time. Six patients had stable disease with a median to progression of 6 weeks. Major toxicity encountered was bone marrow suppression. Aclacinomycin-A appears to have no activity in squamous cancer of the head and neck.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Drug Evaluation; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Naphthacenes

Clinical effects of aclacinomycin-A (ACM) were evaluated in 30 patients with head and neck carcinoma. ACM was continuously administered intravenously at a dose of 20 mg/body for 4 days. After 2 weeks cessation the same courses were repeated. The maximum cumulative dose was 400 mg. Overall objective response rate was 53.3% for head and neck carcinoma, but, the effective rates were different according to histopathological classification of carcinoma. The most responsive tumor was adenocarcinoma. With squamous cell carcinoma the response rate was correlated with the degree of differentiation. Namely, 88.9% of anaplastic squamous cell carcinoma cases responded while the effective rate was only 14.3% for well and moderately differentiated types. In the evaluation of side effects, myelosuppresive toxicity, one of the dose-limiting factors in ACN trials, was slight using in this administration method. Also, any changes in electrocardiograms, occurring during ACM administration, were reversible and negligible. Manifestations of side effects with systemic ACM administration appeared to be less pronounced than those of adriamycin.

Topics: Aclarubicin; Adult; Aged; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Evaluation; Electrocardiography; Female; Head and Neck Neoplasms; Humans; Infusions, Parenteral; Male; Middle Aged; Naphthacenes