aclarubicin and Adenocarcinoma

The study was a Phase II randomized study to evaluate the efficacy of new agents for the treatment of advanced gastric carcinoma. Patients were randomized to receive single agent chemotherapy with mitoxantrone, etoposide, aclacinomycin-A or spirogermanium. The patients were stratified by prior use of chemotherapy, prior doxorubicin use and ECOG performance status. Patients with a history of cardiac disease or prior doxorubicin exceeding a dose of 400 mg/m2 were restrictively randomized to sopirogermanium or etoposide only. One hundred and fourteen patients were registered for the study. Among 98 evaluable patients there were only two partial responses (both in the etoposide arm), and one complete response in the mitoxantrone arm. The median survival on the study was 3.3 months. One hundred and six patients were analyzable for toxicity. There were four treatment-related deaths and four life-threatening toxicities. Because of low response rates and relatively high toxicities the studied compounds were not deemed worth further investigation for advanced gastric cancer.

Topics: Aclarubicin; Adenocarcinoma; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Etoposide; Female; Humans; Male; Mitoxantrone; Organometallic Compounds; Spiro Compounds; Stomach Neoplasms

There were 80 patients with measurable metastatic or unresectable pancreatic cancer randomly assigned to treatment with either DHAD, VP-16, aclacinomycin, or spirogermanium. There were no complete or partial responses. Two deaths from leukopenia occurred in patients treated with DHAD. One patient receiving spirogermanium experienced a seizure. No other life-threatening toxicities occurred. Maximal toxicities were not significantly more frequent with any treatment group. Median survival was 10 weeks, and median time to progression was only 6 weeks, with no difference among these four therapies.

Topics: Aclarubicin; Adenocarcinoma; Adjuvants, Immunologic; Antineoplastic Agents; Etoposide; Female; Humans; Male; Mitoxantrone; Organometallic Compounds; Pancreatic Neoplasms; Spiro Compounds; Survival Rate

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

Aclacinomycin-A (ACLA-A), the new anthracycline antibiotic that produces substantially less cardiotoxicity relative to doxorubicin, was evaluated in a phase II trial for advanced large cell and adenocarcinoma of the lung patients. Twenty-three patients with measurable disease were entered into the trial and received ACLA-A in doses of a weekly infusion of 65 mg/m2 and 85 mg/m2. Eighteen patients were evaluable for response and toxicity. Two patients were evaluable for toxicity only, one died before completion of a full course of therapy, and two did not receive the drug. There were no complete or partial remissions in this study. Three patients had disease stabilization for a median of 10 weeks (range 6-17). Toxicity was mainly hematologic. Nausea and vomiting were moderate. ACLA-A, in the dose schedules used, appears to have no activity in large cell and adenocarcinoma of the lung.

Topics: Aclarubicin; Adenocarcinoma; Adult; Aged; Carcinoma, Small Cell; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Infusions, Parenteral; Leukopenia; Lung Neoplasms; Male; Middle Aged; Naphthacenes; Nausea; Thrombocytopenia; Vomiting

Topics: Aclarubicin; Adenocarcinoma; Adult; Aged; Alopecia; Antibiotics, Antineoplastic; Breast Neoplasms; Drug Evaluation; Female; Humans; Middle Aged; Naphthacenes; Nausea; Neoplasm Metastasis; Neutropenia

In this study, long-circulating Arg-Gly-Asp (RGD)-modified aclacinomycin A (ACM) liposomes were prepared by thin film hydration method. Their morphology, particle size, encapsulation efficiency, and in vitro release were investigated. The RGD-ACM liposomes was about 160 nm in size and had the visual appearance of a yellowish suspension. The zeta potential was -22.2 mV and the encapsulation efficiency was more than 93%. The drug-release behavior of the RGD-ACM liposomes showed a biphasic pattern, with an initial burst release and followed by sustained release at a constant rate. After being dissolved in phosphate-buffered saline (pH 7.4) and kept at 4°C for one month, the liposomes did not aggregate and still had the appearance of a milky white colloidal solution. In a pharmacokinetic study, rats treated with RGD-ACM liposomes showed slightly higher plasma concentrations than those treated with ACM liposomes. Maximum plasma concentrations of RGD-ACM liposomes and ACM liposomes were 4,532 and 3,425 ng/mL, respectively. RGD-ACM liposomes had a higher AUC0-∞ (1.54-fold), mean residence time (2.09-fold), and elimination half-life (1.2-fold) when compared with ACM liposomes. In an in vivo study in mice, both types of liposomes inhibited growth of human lung adenocarcinoma (A549) cells and markedly decreased tumor size when compared with the control group. There were no obvious pathological tissue changes in any of the treatment groups. Our results indicate that RGD-modified ACM liposomes have a better antitumor effect in vivo than their unmodified counterparts.

Topics: Aclarubicin; Adenocarcinoma; Adenocarcinoma of Lung; Animals; Antibiotics, Antineoplastic; Area Under Curve; Cell Line, Tumor; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Stability; Half-Life; Injections, Intravenous; Lipids; Liposomes; Lung Neoplasms; Mice, Inbred BALB C; Mice, Nude; Oligopeptides; Particle Size; Rats; Solubility; Tumor Burden; Xenograft Model Antitumor Assays

Adenocarcinoma of the uterine cervix appears to be increasing in prevalence and it has been suggested that these tumors tend to be less sensitive to radiation therapy and to chemotherapy than squamous carcinomas. In the present study, 29 patients with locally advanced cervical adenocarcinoma (bulky IB-IVB) were treated with neoadjuvant chemotherapy (NAC) using cisplatin, aclacinomycin-A and mitomycin-C, followed by radical surgery or irradiation.. To predict the prognosis and response to the chemotherapy, the expression of apoptosis associated-proteins, p53, p21WAF1/CIP1, Bcl-2 and activated caspase-3 was evaluated for tumor samples by immunohistochemistry.. Of the analyzed clinicopathological factors, the overexpression of p53 was frequently observed in endocervical-type adenocarcinoma, nonresponders to chemotherapy and the grade 0 histologic effect of the chemotherapy. Positive staining of Bcl-2 was frequently observed in the early stage and had a better prognosis than for patients with the negative staining; however, there was no correlation between responders and nonresponders to chemotherapy. The expression of p21WAF1/CIP1 and caspase-3 was not correlated to the clinicopathological factors.. In this study, the overexpression of p53 was found to be a factor to predict the chemoresistance and positive expression of Bcl-2 indicated as a better prognostic value. For p21WAF1/CIP1 and caspase-3, further analysis is necessary.

Topics: Aclarubicin; Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Caspase 3; Caspases; Cisplatin; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Female; Humans; Immunohistochemistry; Middle Aged; Mitomycin; Neoadjuvant Therapy; Prognosis; Proto-Oncogene Proteins c-bcl-2; Tumor Suppressor Protein p53; Uterine Cervical Neoplasms

Patients with myelodysplastic syndrome (MDS) show a relatively high incidence of developing cancers. However, it is extremely rare that synchronous double cancers develop in an MDS patient. We report a case of MDS that progressed rapidly into erythroleukemia (M6 by French-American-British classification) complicated by gastric cancer and carcinoma of the papilla of Vater. A 66-year-old man was admitted because of pancytopenia with peripheral blasts. A diagnosis of MDS (with refractory anemia with excess of blasts in transformation [RAEB-T]) was made by bone marrow examination. Chromosome analysis revealed 46,XY. An early gastric cancer was also diagnosed by endoscopic examination. The peripheral blasts gradually proliferated and the disease progressed to M6. A chromosome abnormality 46,XY,del(1)(q42) was detected at the leukemic transformation. A CAG (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor) regimen was started as a remission-induction therapy. However, obstructive jaundice developed and a marked dilatation of bile ducts was observed by abdominal computed tomography (CT). A carcinoma of the papilla of Vater was detected by endoscopy. As remission was achieved and the pancytopenia improved, the patient subsequently underwent a surgical jejuno-choledochostomy to manage the jaundice. However, the leukemia relapsed thereafter and additional chromosome abnormalities including der(5)t(5;10)(p15:q11) were observed.

Topics: Aclarubicin; Adenocarcinoma; Aged; Ampulla of Vater; Anemia, Refractory, with Excess of Blasts; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cholestasis, Extrahepatic; Chromosome Aberrations; Chromosome Disorders; Common Bile Duct Neoplasms; Cytarabine; Disease Progression; Granulocyte Colony-Stimulating Factor; Humans; Karyotyping; Leukemia, Erythroblastic, Acute; Male; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Pancytopenia; Stomach Neoplasms

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

The in vitro drug sensitivity of gastric cancer tissues obtained from 40 patients with advanced cancer was compared in terms of the pathological classifications which were assigned according to the General Rules for the Gastric Cancer Study in Surgery and Pathology in Japan. Cases of poorly differentiated adenocarcinoma which had penetrated the serosa were evaluated using the succinate dehydrogenase inhibition (SDI) test for determining the in vitro chemosensitivity. The sensitivity of the stage III group to cisplatin was higher than that of the stage IV group. Although there were no statistical differences in drug sensitivities according to macroscopic findings (Borrmann's classification), the expanding growth type was more susceptible that the infiltrating type to cisplatin, aclacinomycin A (ACR) and carboquone (CQ) microscopically. In cases of lymph node metastasis [n(+)] the sensitivity to cisplatin, ACR, CQ, adriamycin and mitomycin C was less than in those with or without primary lymph node metastasis [n(-)]; lymphatic invasion in the gastric wall (ly) was a significant factor linked to drug resistance. Our findings indicate that the evaluation of tumor pathology is important in predicting the chemosensitivity of poorly differentiated gastric cancers.

Topics: Aclarubicin; Adenocarcinoma; Antineoplastic Agents; Carbazilquinone; Cisplatin; Doxorubicin; Drug Screening Assays, Antitumor; Humans; In Vitro Techniques; Mitomycin; Neoplasm Invasiveness; Neoplasm Staging; Stomach Neoplasms

Carcinomatous metastatic involvement of the spleen usually indicates a widespread malignant disease. Solitary metastatic lesions in the spleen are exceedingly rare. The literature contains fewer than 16 cases. In this paper we report a case of a solitary metastatic lesion of the spleen arising from a serous cystadenocarcinoma of the ovary 5 years after the initial operation. A splenectomy was performed followed by smooth postoperative course.

Topics: Aclarubicin; Adenocarcinoma; Aged; Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Female; Humans; Hysterectomy; Ovarian Neoplasms; Peplomycin; Splenectomy; Splenic Neoplasms

Topics: Aclarubicin; Adenocarcinoma; Adult; Aged; Gastrointestinal Neoplasms; Humans; Middle Aged

Fourteen patients with recurrent gynecological adenocarcinomas (nine with endometrial cancer and six with ovarian cancer) were treated with cisplatin given by 14-day continuous infusion at a daily dose of 10 mg/m2 in combination with aclarubicin (ACR) at a dose of 20 mg/body on alternate days during each 14-day course. The daily dose of cisplatin was given with 1 liter of fluids; no diuretics were administered. The overall response rate was 71.4% (50% in endometrial cancer and 100% in ovarian cancer). It was especially interesting that a 100% response rate was obtained in five patients previously treated with cisplatin; i.e., the present cisplatin dosing schedule was highly effective as second-line therapy in these patients. No renal or gastrointestinal toxicity was observed. These results were pharmacokinetically explained by the plasma concentration of filterable platinum. A low-level, plateau-like curve with a great area under filterable [Pt]-time curve (AUC) seemed to ensure exposure of cancer cells to filterable platinum for sufficiently long periods and freedom from gastrointestinal and renal side effects.

Topics: Aclarubicin; Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cystadenocarcinoma; Drug Administration Schedule; Female; Humans; Middle Aged; Ovarian Neoplasms; Recurrence; Uterine Neoplasms

The combination of cisplatin, doxorubicin, cyclophosphamide, and megestrol acetate was used to treat 15 patients with recurrent and metastatic endometrial cancer. Four patients had a complete response and one patient had a partial response, yielding a total response rate of 33%. Five patients had stable disease. The median survival for the whole group was 38 weeks. The median survival for responders was 60 weeks, and that for nonresponders was 21 weeks. The median progression-free survival for the whole group was 17 weeks. The median progression-free survival for responders was 32 weeks, and that for patients with stable disease was 25 weeks. The toxic reactions noted were primarily nausea, vomiting, and myelosuppression. The combination of cisplatin, doxorubicin, cyclophosphamide, and megestrol acetate has modest effectiveness in the treatment of metastatic or recurrent carcinoma of the endometrium.

Topics: Aclarubicin; Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Female; Humans; Megestrol; Megestrol Acetate; Neoplasm Recurrence, Local; Peplomycin; Uterine Neoplasms

We report on a 62-year-old patient with a metastasising, only poorly differentiated follicular thyroid carcinoma, who was subjected postoperatively to chemotherapy with Aclarubicin. Aclarubicin (Aclaplastin) is a new cytostatic agent, from the group of anthracyclines, with fewer side effects and clearly diminished cardiotoxicity. The patient died suddenly after two treatment cycles with clinical symptoms of cardiac insufficiency; the post-mortem examination, however, revealed that two metastases in the myocardium might have been the cause of death; toxic myocardial damage could be excluded histologically. Upon occurrence of cardial symptoms and signs during therapy with cytostatic agents of thyroid carcinoma with Aclarubicin, whose cardiotoxic side effects are known, the possibility of metastatic spread in the myocardium should, nevertheless, also always be considered in the differential diagnosis.

Topics: Aclarubicin; Adenocarcinoma; Death, Sudden; Heart Neoplasms; Heart Ventricles; Humans; Male; Middle Aged; Thyroid Neoplasms

Topics: Aclarubicin; Adenocarcinoma; Aged; Antibiotics, Antineoplastic; Carcinoma; Female; Humans; Male; Middle Aged; Naphthacenes; Thyroid Neoplasms

The chemosensitivities of 41 poorly differentiated gastric cancer tissues were compared with that of 16 well differentiated tissues, using the in vitro succinate dehydrogenase inhibition test. These human tissues obtained at the time of surgery were exposed to six different antitumor drugs: carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP) and 5-fluorouracil (5-FU). The chemosensitivity was determined as positive when the succinate dehydrogenase (SD) activity of the drug exposed cells was decreased to below 50% of that of control cells, on day 3 of exposure. Decrease in SD activity was remarkable in the poorly differentiated tissues, compared to the well differentiated tissues, exposed to ADM, MMC, DDP and 5-FU. The sensitive rates were higher in the poorly differentiated tissues than in the well differentiated tissues, against all six antitumor drugs. Sixty-three per cent of the poorly differentiated tissues were sensitive to more than three antitumor drugs, in an identical tissue, but the rate was only 19% in the well differentiated tissues. The resistant rates to all drugs tested were 20% in the poorly differentiated and 31% in the well differentiated tissues. This would indicate that patients with a poorly differentiated gastric cancer will probably show a better response to antitumor drugs, compared to those with a well differentiated type.

Topics: Aclarubicin; Adenocarcinoma; Adenocarcinoma, Mucinous; Adenocarcinoma, Papillary; Antineoplastic Agents; Carbazilquinone; Cisplatin; Doxorubicin; Fluorouracil; Humans; In Vitro Techniques; Mitomycin; Mitomycins; Naphthacenes; Stomach Neoplasms; Succinate Dehydrogenase

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

Male F1 hybrid rats bearing the R-3327 transplantable prostatic adenocarcinoma demonstrating similar growth patterns within the original sample of animals were carefully separated into control and treatment groups. This assured treatment of tumors with similar cell kinetics within each group. In the first study, two separate drug protocols were investigated by intraperitoneal injection, namely cyclophosphamide (100 mg/kg) once every 4 weeks for 8 weeks and scheduled methotrexate (7.5 mg/kg) followed in 90 minutes by 5-fluorouracil (50 mg/kg) once each week for 8 weeks. Excellent suppression of tumor growth was obtained with each treatment protocol. Both were significant at the 0.01 level. In the second study, methotrexate (100 mg/kg) intraperitoneally once each week for 6 weeks, aclacinomycin-A intraperitoneally once each week for 4 weeks, and ketoconazole (60 mg/kg) via gavage 5 times a week for 6 weeks were administered to the animals in each respective group. Aclacinomycin-A and ketoconazole showed significant suppression of tumor growth at the 0.01 and 0.05 levels, respectively. Methotrexate suppressed tumor growth, but did not reach levels of significance over the duration of the study (0.2 less than P less than 0.3).

Topics: Aclarubicin; Adenocarcinoma; Animals; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Drug Administration Schedule; Fluorouracil; Ketoconazole; Male; Methotrexate; Naphthacenes; Neoplasm Transplantation; Prostatic Neoplasms; Rats

Intrapleural treatment with aclacinomycin combined with closed tube thoracostomy was used in 7 patients with malignant pleural effusion. Five patients had no recurrence of effusion 3 months after the treatment. Aclacinomycin levels were much higher in blood cells than in plasma, and metabolites were present as the active form. We posit that the local instillation of aclacinomycin is indicated in the management of malignant pleural effusion.

Topics: Aclarubicin; Adenocarcinoma; Adult; Aged; Drainage; Female; Humans; Intubation; Lung Neoplasms; Male; Middle Aged; Naphthacenes; Pleural Effusion; Thorax

Topics: Aclarubicin; Adenocarcinoma; Adult; Aged; Antibiotics, Antineoplastic; Drug Evaluation; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Naphthacenes; Vomiting

A series of experiments with ACM was performed to evaluate the effect for local treatment of malignant pleurisy from the view points of (1) clinical response, (2) pharmacokinetics following intrapleural administration, and (3) pleural reaction. The results were as follows: (1) In 6 patients with malignant pleural effusion, ACM was intrapleurally administered at a dose of 40 mg. In 4 out of the 5 evaluable cases, an extreme decrease in the pleural fluid volume and suppression of reswelling were observed, including 2 cases found to be negative for tumor cells upon cytodiagnosis. (2) In 5 patients, the pharmacokinetics was studied by using compartment model. The clearance curves of ACM in pleural fluid were described by a two-compartment model. The mean half lives of initial phase and terminal phase were 0.78 hr, and 15.28 hr, respectively. The time to reach the maximal whole blood level was 1 to 2 hrs after pleural administration, followed by a slow decline. (3) The pleural reaction to ACM was studied in rabbits by scanning and transmission electron microscope. At a dose of 4 mg per kg of body weight, the shortened microvilli, the degenerated mesothelial cells and the disappearance of basement membrane were observed. On the basis of these findings, we suggest that ACM might be an agent of choice in the treatment of malignant pleurisy.

Topics: Aclarubicin; Adenocarcinoma; Aged; Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Carcinoma, Small Cell; Female; Humans; Lung Neoplasms; Male; Middle Aged; Naphthacenes; Pleural Effusion; Rabbits