aclarubicin and Brain-Neoplasms

Combination chemotherapy of Cis-platinum with Aclarubicin was performed in patients with intracranial alveolar rhabdomyosarcoma. These patients were treated with Cis-platinum (20 mg/day) and Aclarubicin (20 mg/day) for 5 days. After two trials with about a four-week interval, complete tumor regression on CT scan was observed. Mild gastrointestinal toxicity was observed in these patients but the symptoms were transient and soon disappeared. No other side effects appeared, on or after treatment. This result demonstrated that combination chemotherapy of Cis-platinum and Aclarubicin is an effective regimen for remission induction chemotherapy in patients with intracranial sarcoma.

Topics: Aclarubicin; Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cisplatin; Clinical Trials as Topic; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Naphthacenes; Rhabdomyosarcoma

Topics: Aclarubicin; Adult; Aged; Aziridines; Azirines; Benzoquinones; Brain Neoplasms; Carcinoma, Bronchogenic; Drug Evaluation; Female; Humans; Infusions, Parenteral; Lung Neoplasms; Male; Middle Aged; Naphthacenes; Random Allocation

Traditional glioma chemotherapy with those second-line drugs such as anthracyclines usually failed because they are inaccessible to blood-brain barrier (BBB) in tumor. In our study, we incorporated aclarubicin (ACL) into cationic albumin-conjugated pegylated nanoparticle (CBSA-NP-ACL) to determine its therapeutic potential of rats with intracranially implanted C6 glioma cells. When labeled with fluorescent probe, 6-coumarin, CBSA-NP was shown to accumulate much more in tumor mass than nanoparticle without conjugated CBSA (NP) 1 hr post intravenous injection, as well as better retention after 24 hr. Tumor drug concentration of CBSA-NP-ACL displayed 2.6- and 3.3-fold higher than that of NP-ACL and ACL solution 1 hr post injection, while 2.7 and 6.6-fold higher after 24 hr, respectively. Moreover, using tumor microdialysis sampling, AUC(0-24 hr) of free drug amount in tumor interstitium delivered by CBSA-NP-ACL was about 2.0- and 2.7-fold higher than that of NP-ACL and ACL solutions, respectively. When the tumor rat model was subjected to 4 cycles of 2 mg/kg of ACL in different formulations, a significant increase of median survival time was found in the group of CBSA-NP-ACL compared with that of saline control animals, animals treated with NP-ACL and ACL solution. By terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling, CBSA-NP-ACL can extensively make the tumor cell apoptosis. Histochemical evaluation by periodic acid Shiff staining and biochemical analysis depicted that the incorporation of ACL into CBSA-NP reduced its toxicity to liver, kidney and heart. Besides, CBSA-NP-ACL was not shown to open tight junction evaluated by BBB coculture. It was concluded that CBSA-NP-ACL could have a therapeutic potential for treatment of glioma.

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Brain Neoplasms; Drug Carriers; Glioma; Male; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Serum Albumin; Tissue Distribution

A 46-year-old woman had undergone a mastectomy in 1994, and metastases to the lung, bones and liver were detected in 1998. Brain metastases were detected later. Chemotherapy consisting of docetaxel, aclarubicin and UFT was administered, and image diagnosis revealed that CR was achieved. The chemotherapy was continued on a long-term basis, both as an inpatient and outpatient. The total administered doses have reached 2,000 mg of docetaxel and 1,000 mg of aclarubicin. The CR is being maintained as of this writing, 2 years and 4 months after the detection of the metastases. The patient's course continues to be monitored.

Topics: Aclarubicin; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Docetaxel; Drug Administration Schedule; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Middle Aged; Paclitaxel; Taxoids; Tegafur; Uracil

Thirteen patients with metastatic brain tumors were treated by combined chemotherapy with cisplatin and aclarubicin hydrochloride. Initial response to this therapy was evaluated by the changes of tumor size on CT scan and clinical state during and after the treatment. The side effects and the causes of death were also studied. Nine cases demonstrated complete remission and 3 cases revealed partial response on CT scan. In short, over all response rate was 92%. Clinical state evaluated by Karnofsky scale was improved in 9 out of 13 cases. As the side effects, there were mild myelosuppression, nausea and vomiting, which didn't persist for a long time. The cause of death was mainly due to recurrence of primary lesion. The tissue concentration of aclarubicin hydrochloride was measured in 6 patients, of which mean value was 0.558 microgram/g at 15 min. The concentration was thought high enough to kill tumor cells.

Topics: Aclarubicin; Adult; Aged; Antibiotics, Antineoplastic; Brain; Brain Neoplasms; Cisplatin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naphthacenes

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

Augmentation of cytotoxicity against cultured human tumor cell lines (5 gliomas, 2 neuroblastomas, 2 sarcomas) using a combination of Aclarubicin (ACR) and Cisplatinum (CDDP) was analysed in vitro from the viewpoints of cell growth inhibition and alteration of the DNA histogram. Synergistic effects of the combination of the two agents were observed in 7 of the 9 cell lines. In sarcoma cell lines, effects were demonstrated even by a low dose of 0.1 microgram/ml CDDP and 0.01 microgram/ml ACR. Flow cytometry studies of the DNA histogram showed increase of accumulation in the S phase following the G2-M phase and reduction of G1 phase cells in response to the combination. From the present experimental studies in vitro, it is concluded that combination chemotherapy with ACR and CDDP may be effective for sarcoma and ACNU-resistant glioma. The mechanism of the synergistic effect produced by the combination is suggested to be impairment of RNA synthesis by ACR which prevents the repair of DNA damage induced by CDDP.

Topics: Aclarubicin; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cell Cycle; Cell Line; Cells, Cultured; Cisplatin; Drug Synergism; Humans; Naphthacenes

The effects of heat and antitumor drugs on malignant brain tumor cell lines were studied. A human glioblastoma cell line (SKMG1) and rat malignant brain tumor cell lines (T9, EB 679 and TR 481) were used in this experiment. Five different modalities of treatment with heat and drugs were used as follows: (Group 1) exposure to heat alone at 42 degrees C for one hour; (Group 2) exposure to antitumor drug alone for one hour (ACNU 2.5 or 5 micrograms/ml, ACR 0.02 micrograms/ml and CDDP 1 microgram/ml); (Group 3) simultaneous exposure to heat at 42 degrees C and drug for one hour; (Group 4) heat at 42 degrees C given first for one hour, followed by one hour exposure to drug one hour later ("preheating"); (Group 5) drug given first for one hour, followed by one hour exposure to heat at 42 degrees C one hour later ("postheating"). After each treatment, the inhibition rate at 4 days was evaluated and compared for each group. A synergistic effect was observed in Group 3. For example, when T9 cells were exposed to ACNU and to heat at 42 degrees C at the same time for one hour, inhibition rate was 78%, while the rates for Group 1 and Group 2 were 7% and 21%, respectively. The cytotoxicity of simultaneous treatment with antitumor drugs (ACNU, ACR and CDDP) and hyperthermia at 42 degrees C was apparently superior to that of other treatment modalities.

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cell Line; Cisplatin; Combined Modality Therapy; Glioma; Humans; Hyperthermia, Induced; Naphthacenes; Nimustine; Nitrosourea Compounds; Rats

The effects of the anticancer drugs Nimustine (ACNU), Aclacinomycin A (ACR), Adriamycin (ADM), Bleomycin (BLM), Cisplatin (CDDP), and 5-Fluorouracil (5-FU) on the multicellular spheroid of a chemically-induced 9L rat glioma was studied. The multicellular spheroid in which cells grow in vitro as three-dimensional aggregates represents a biological model, which is intermediate between monolayer cells in vitro and solid tumors. Spheroids were initiated in bacteriological grade petri dishes seeded with 10(6) 9L rat glioma cells, cultured for four days and thereafter transferred and further developed in a spinner flask. Spheroids of 200-400 micron diameter were sorted and exposed for 24 hours to 5-FU and one hour for other drugs. After treatment both cytotoxic effect and growth delay were analyzed. Following disaggregation using collagenase, pronase and DNAase, cytotoxic effect on multicellular spheroids was measured by colony forming assay and were compared with those effects on 9L monolayer culture cells in the exponential growth. For growth delay assay, multicellular spheroids were individually transferred to 16 mm well containing 0.4 ml agarose base and 2 ml culture medium. Spheroid size was measured twice a week and growth curves were drawn. The growth delay was determined as the treated group vs. control differences in time required to a size four times that of the initial volume. For cells both in the monolayer culture and the multicellular spheroid, the dose response curve for ADM, BLM and 5-FU was "biphasic" and that for ACNU, ACR and CDDP "shoulder-threshold" type.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aclarubicin; Animals; Antineoplastic Agents; Brain Neoplasms; Cell Division; Cell Survival; Cells, Cultured; Cisplatin; Dose-Response Relationship, Drug; Doxorubicin; Glioma; Naphthacenes; Nimustine; Nitrosourea Compounds; Rats; Tumor Stem Cell Assay