aclarubicin and Ovarian-Neoplasms

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Daunorubicin; Doxorubicin; Female; Glycosides; Hodgkin Disease; Humans; Leukemia; Lung Neoplasms; Lymphoma; Naphthacenes; Ovarian Neoplasms; Sarcoma

Two hundred fifty-nine patients with ovarian cancers were treated with the combination of CDDP, aclarubicin and tegafur. Ninety-seven of them had macroscopic diseases during the combination chemotherapy, and the overall anti-tumor response rate (CR + PR) for these patients was 54.6%. It was 60.0% for the 80 cases with epithelial ovarian cancer among them. The median survival time for the antitumor responders was 18 months, against 7 months for the non-responders and 18 months for 103 patients with advanced ovarian cancer (stage III-IV).

Topics: Aclarubicin; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Evaluation; Female; Follow-Up Studies; Humans; Japan; Middle Aged; Multicenter Studies as Topic; Ovarian Neoplasms; Prognosis; Remission Induction; Reoperation; Tegafur

We investigated the anticancer activity of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, on weakly doxorubicin (Dox)-resistant SK-OV-3 ovarian cancer cells, and elucidated the relationship between its anticancer activity and accumulation in cells compared with those of Dox. Accumulation of ID-6105 in the cells was time-and concentration-dependent, a result of drug-induced cytotoxicity in the cells. SK-OV-3 cells were preloaded with ID-6105 or Dox for 12 h at concentrations ranging from 100 to 2000 nM and then incubated with drug-free medium for 0-48 h. Cell viability was measured using a proliferation-based assay (XTT assay). The inhibitory effects of ID-6105 on cell viability were more pronounced than those of Dox. The IC(50) values of ID-6105 after 24-and 48-h incubation with drug-free medium were 1.58 and 0.084 microM, while those of Dox were 2 and 0.334 microM, respectively. To investigate the relationship between the intracellular levels and the cytotoxic effects of the drugs, we preloaded SKOV-3 cells with ID-6105 or Dox (100-2000 nM) for 12 h and then measured the intracellular levels of drugs by HPLC in drug-free medium for 0-48 h. After preloading the drugs, the intracellular concentrations of ID-6105 at time 0 were 1.3-, 1.8-, and 1.4-fold larger than those of Dox at initial concentrations of 500, 1000, and 2000 nM, respectively. The extent of ID-6105 accumulation in the cells was more pronounced than that of Dox. These findings suggest that ID-6105 effluxed less from the cells than Dox, resulting in its extensive cytotoxicity compared with that of Dox. These results show that accumulation of ID-6105 within tumor cells may be important for the inhibitory effects of this drug in cancer cells. ID-6105 has an antiproliferative effect on SK-OV-3 cells that is due to its cytotoxicity. This effect is more pronounced than that of Dox, and may be attributed to extensive accumulation of ID-6105 in the cells.

Topics: Aclarubicin; Antibiotics, Antineoplastic; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Chromatography, High Pressure Liquid; Doxorubicin; Female; Humans; Indicators and Reagents; Ovarian 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

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

Six patients with recurrent ovarian cancer who had prior chemotherapy were studied for the clinical efficacy of CDDP-ACR treatment. Five out of the 6 had received CDDP a total doses of 1,320, 780, 750, 475, and 340 mg. CDDP-ACR therapy consisted of continuous infusion of CDDP at a daily dose of 10 mg/m2 over 14 days (total CDDP doses; 140 mg/m2) and of intermittent infusion of ACR (aclarubicin) at a dose of 20 mg/body every other day (total ACR doses: 140 mg). There were one CR and five PR and a response rate up to 100% was noted. Toxicity was manifested in slight nausea or vomiting, but there was no nephrotoxicity. However bone marrow was severe. Thrombocytopenia less than 50,000/mcl in 4 pts (67%) and leukopenia less than 1,000 mcl in 3 pts (50%). The mean filterable platinum exposure measured by area under the concentration-time curve (AUC) was as high as 19.7 +/- 6/0 mg.hr/ml. In conclusion the bone marrow toxicity in this regimen was severe, but the therapeutic efficacy was promising. Further studies on the appropriate infusion time and the minimum effective dose of CDDP are needed.

Topics: Abdominal Neoplasms; Aclarubicin; Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cystadenocarcinoma; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Leukopenia; Lymphatic Metastasis; Middle Aged; Ovarian Neoplasms; Platinum; Recurrence; Remission Induction; Thrombocytopenia

Aclacinomycin A (ACM) in a daily dose of 30 mg/m2 was infused over 1 h on 4 consecutive days to 50 patients. Myelotoxicity was acceptable, nausea and vomiting was frequent, hair loss was mild. Grade 1-2 cardiac rhythm abnormalities were observed in 12% of the patients. Between days 1 and 4 the heart rate and the corrected Q-T interval increased while the amplitude of the T wave decreased significantly, cardiac contractility remained unchanged. In 24 evaluable breast cancer patients 1 complete remission (4%) and 2 partial remissions (8%) lasting for only 2-3 months were seen. None of the 8 patients suffering from ovarial cancer benefitted from ACM therapy.

Topics: Aclarubicin; Adult; Aged; Antibiotics, Antineoplastic; Bone Marrow; Breast Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Electrocardiography; Female; Heart; Humans; Male; Middle Aged; Naphthacenes; Neoplasms; Ovarian Neoplasms

Sixteen women with advanced epithelial ovarian carcinoma were treated with Aclacinomycin-A 40 mg/M2 given as a weekly infusion for four consecutive weeks followed by a two week rest period. All had failed prior chemotherapy. No responses were observed. Nausea and vomiting were the most frequent side effect. Myelosuppression was minimal. This dose and schedule of Aclacinomycin-A are not recommended for further trials in ovarian carcinoma.

Topics: Aclarubicin; Adult; Aged; Antibiotics, Antineoplastic; Drug Evaluation; Female; Humans; Middle Aged; Naphthacenes; Ovarian Neoplasms

Combination chemotherapy regimens have produced a pathological complete response rate of only 1%-25% in patients with advanced ovarian cancer. Patients with small-volume residual disease after treatment are refractory to further systemic therapy, and most eventually die of their disease. Intraperitoneal (i.p.) chemotherapy, particularly with adriamycin or cisplatin has shown promise in these patients. However, the dose-limiting painful peritonitis associated with i.p. adriamycin makes this regimen potentially too toxic for many patients. Aclacinomycin A, another anthracycline antibiotic, has been found to have activity against a wide variety of murine tumors and human xenografts. It has also demonstrated clinical efficacy in phase I and II trials against refractory ovarian cancer and has less pronounced vesicant properties than adriamycin, making it an ideal candidate for i.p. use in ovarian cancer patients. In vitro clonogenic assays utilizing a battery of adriamycin-sensitive and -resistant human ovarian carcinoma cell lines have shown that aclacinomycin A is more cytotoxic than adriamycin in all cell lines tested. In addition, aclacinomycin A was found to prolong survival in a nude mouse xenograft of i.p. human ovarian cancer. These results have provided the experimental rationale for an ongoing clinical trial of i.p. aclacinomycin in refractory ovarian cancer patients at the Medicine Branch, NCI.

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Cell Line; Drug Evaluation; Female; Humans; Injections, Intraperitoneal; Mice; Mice, Inbred BALB C; Mice, Nude; Naphthacenes; Neoplasm Transplantation; Ovarian Neoplasms; Transplantation, Heterologous; Tumor Stem Cell Assay

The subrenal capsule assay in normal immunocompetent mice was used to test the responsiveness of ovarian cancer to combination chemotherapy. Of the assays, 42 were of untreated tumors and 19 of previously treated tumors. Fifty-nine (97%) of the assays were evaluable. The previously treated tumors were less sensitive than the untreated ones. Of the treated tumors 44% were sensitive, 33% intermediately sensitive, and 22% resistant versus 56, 44, and 0%, respectively, of the untreated tumors (P less than .01). Repeat assays for the tumors of seven patients were performed successfully after five to eight courses of therapy with the combination of doxorubicin, cyclophosphamide, and cisplatin. The responsiveness to this combination had weakened significantly (P less than .01); the response of only one tumor remained unchanged. The rates of resistance to the drug combinations doxorubicin-cyclophosphamide-cisplatin, doxorubicin-cyclophosphamide-tegafur, and cyclophosphamide-vincristine were 11, 10, and 21%, respectively; there was, however, considerable interindividual variation in tumor responses to these combinations. Of other combinations, hexamethylmelamine combined with 4-epidoxorubicin, aclarubicin, or chlorambucil and cisplatin had effect, whereas the combinations of cisplatin and etoposide and of tegafur and methotrexate or mitomycin were quite ineffective, as measured by the assay. The reliability of the subrenal capsule assay in normal immunocompetent mice is discussed, and it is concluded that the assay can be used to assess the response of ovarian cancer to chemotherapy, including multidrug therapy, without routine histologic control.

Topics: Aclarubicin; Adolescent; Adult; Aged; Altretamine; Animals; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chlorambucil; Cisplatin; Cyclophosphamide; Cystadenocarcinoma; Doxorubicin; Epirubicin; Etoposide; Female; Humans; Methotrexate; Mice; Middle Aged; Mitomycins; Naphthacenes; Neoplasm Transplantation; Ovarian Neoplasms; Tegafur; Tumor Stem Cell Assay; Vincristine