pirarubicin and Uterine-Neoplasms

We present the unusual case of a 27-year-old Japanese woman who exhibited recurrences of metastatic tumors from uterine leiomyosarcoma after five operations. Chemotherapy with cisplatin, pirarubicin, and cyclophosphamide was ineffective. Substituting ifosfamide for cyclophosphamide, we obtained a complete response. The Gynecologic Oncology Group (GOG) in the United States has recognized the efficacy of ifosfamide and mesna in the treatment of patients with advanced or recurrent uterine sarcomas. Here we report on the efficacy of ifosfamide in addition to cisplatin and pirarubicin.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Female; Humans; Ifosfamide; Immunosuppressive Agents; Leiomyosarcoma; Neoplasm Recurrence, Local; Remission Induction; Uterine Neoplasms

The effect of the anthracycline analogue, pirarubicin, on cardiac function was examined. One hundred and four patients with gynecologic malignancies were treated with 40-50 mg/body THP ADM every 3 to 4 weeks by iv bolus injection. Three out of 104 cases that had developed cardiac failure received more than 1,500 mg. One case receiving 1,340 mg developed cardiac failure and expired 3 years after completion of treatment for malignancy. From the above experience, it is concluded that the MTD of pirarubicin seems to be 1,500 mg/body or 1,100 mg/m2.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Doxorubicin; Drug Administration Schedule; Electrocardiography; Female; Heart; Humans; Middle Aged; Myocardium; Ovarian Neoplasms; Uterine Neoplasms

A 57-year-old female patient complained of atypical genital bleeding and a noxious emanation from her navel. A histological examination of the uterine body and the navel area confirmed a diagnosis of adenocarcinoma. We diagnosed it as IVb stage of uterine corpus cancer with a Sister Mary Joseph's nodule. We selectively administered intraarterial injection chemotherapy (Cisplatin 120 mg, Pirarubicin 40 mg) in the uterus and navel area (three times, once every three weeks) prior to surgery. The isolated uterus showed that the cancerous tissue had been eradicated, and we judged the cancer to be grade 3 following histopathological effective grading standards. The metastasis exhibited extreme shrinkage, but affirmed changes in the tumor quality. Currently, the patient is receiving maintenance therapy of 600 mg of Hysron H, and 600 mg of UFT. There are no indications of recurrence, and the patient is progressing well.

Topics: Abdominal Neoplasms; Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Doxorubicin; Female; Humans; Infusions, Intra-Arterial; Middle Aged; Remission Induction; Umbilicus; Uterine Neoplasms

We have studied the pharmacokinetics and metabolism of pirarubicin (4'-O-tetrahydropyranyldoxorubicin) in six patients included in an EORTC phase II study. Pirarubicin was injected as an i.v. bolus of 5 min on 3 consecutive days at a dose of 20 mg/m2 per day. Blood samples were collected at regular times after each injection. Urine was collected over 12 h periods for 3 days and then over 24 h periods. Pirarubicin and metabolites were extracted on Sep-pak cartridges, and analyzed by HPLC with fluorometric detection. Unchanged pirarubicin followed three similar plasma concentration curves, which could be fitted by a two-compartment model with successive half-lives of 22.0 min and 12.7 h. Total plasma clearance of the drug was 90 l/h/m2 and total volume of distribution 1380 l/m2. Doxorubicin was the main metabolite in plasma after an injection of pirarubicin; its concentration was lower than that of pirarubicin but progressively increased from day to day and exceeded the level of pirarubicin 8 h after the 3rd injection of the drug until the end of the blood sampling. Pirarubicinol and doxorubicinol were also metabolites of pirarubicin in plasma; pirarubicinol followed similar plasma concentration curves during the 3 days of treatment whereas doxorubicinol progressively increased from day to day. Total urinary excretion represented about 6% of the dose injected. The same metabolites as in plasma were found in urine. Whereas the total amount of pirarubicin and pirarubicinol was the same in urine during the 24 h after each injection, the amounts of doxorubicin and doxorubicinol excreted increased from day to day, so that doxorubicin became progressively the main compound in urine after the end of the treatment. The progressive accumulation of pirarubicin metabolites (doxorubicin and doxorubicinol) after the repetitive injections of pirarubicin are probably due to the protracted half-lives of these compounds as compared to that of pirarubicin.

Topics: Adult; Aged; Chromatography, High Pressure Liquid; Doxorubicin; Drug Evaluation; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Uterine Neoplasms

We conducted a joint phase II study in 76 patients with gynecological cancer (42 patients with ovarian cancer, 22 patients with cervical cancer, 10 patients with endometrial cancer and 2 patients with vaginal cancer). The response rate was 25.0% in the patients with ovarian cancer, 13.3% in those with cervical cancer, and 28.6% in those with endometrial cancer. The overall response rate was 23.1%. When the patients were classified according to dose schedules, the highest response rate was obtained in the group administered THP-ADM at a dose of 60 mg per body by single i.v. injection at 3-week intervals. Such side effects as myelosuppression and gastrointestinal disturbances were observed, but alopecia, a marked side-effect of ADM administration, was mild, and no cardiac toxicity was seen in any of the patients.

Topics: Adult; Aged; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Genital Neoplasms, Female; Humans; Middle Aged; Ovarian Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms; Vaginal Neoplasms

THP-ADM is a new antitumor antibiotic which belongs to the anthracycline group. This agent was administered to 42 histology proven various malignant disease patients with a schedule of 60-80 mg per body (40-55 mg per m2) iv bolus, every three weeks. THP-ADM administration revealed mild upper GI toxicity (vomiting 19%, stomatitis 21%) and leukopenia (less than 2,000 per mm3) in 80% and thrombocytopenia (less than 60,000 per mm3) in 38% with good rebound. There was no signs or symptoms of cardiac failure including the patient who had received 740 mg per body (500 mg per m2). Definite response (CR, PR) was observed in ovarian carcinoma 4/11, cervix carcinoma 2/7, breast carcinoma 1/6, malignant lymphoma 5/5 and mesothelioma 1/2. Furthermore, some response (MR) was observed in lung metastasis from endometrial carcinoma 2/4, and stomach carcinoma 1/3. The above indicated usefulness of this agent and further study should be continued, especially a controlled study with adriamycin.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Doxorubicin; Drug Evaluation; Female; Humans; Lymphoma; Male; Mesothelioma; Middle Aged; Ovarian Neoplasms; Sarcoma; Stomach Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms