mitolactol and Sarcoma

To study the results of combination chemotherapy of uterine sarcoma after operation and recurrent tumor.. One hundred seventy-four cases of three major pathological subtypes of uterine sarcomas were treated in the Cancer Hospital from 1960 to 1996. Clinical data were analyzed of 51 cases of uterine sarcomas treated with postoperative adjuvant chemotherapy and 38 cases with recurrent tumors received 98 courses of chemotherapy. They were divided into 4 groups according to the adjuvant chemotherapy regimen: single drug, VAC, VAD, and other regimens. Chemotherapy regimens for recurrent tumors were VAD, PA/PAC, and other combination regimens including etoposide, ifosfamide, cisplatin, adriamycin.. The 5-year survival rate of stage I-II uterine sarcoma patients was 54.9% receiving adjuvant chemotherapy. It was 72.7% in VAD group which was significantly higher than that in other regimen groups. The survival rate was related to the number of chemotherapy course. The chemo-sensitivity of various pathological types of recurrent uterine sarcomas was not different.. The 5-year survival rate does not improve in patients with stage I-II uterine sarcomas given postoperative chemotherapy. VAD is among the best regimens and at least 3 courses should be performed. The results of new treatment regimens such as EPA, IA, etc., must await further clinical observation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Doxorubicin; Drug Therapy, Combination; Etoposide; Female; Humans; Mitolactol; Mitomycins; Neoplasm Recurrence, Local; Postoperative Period; Retrospective Studies; Sarcoma; Survival Rate; Uterine Neoplasms

To explore the expression of multidrug resistance gene 1 ( MDR1), glutathione-S-transferases-pi (GST-pi) in osteosarcoma and soft tissue sarcoma tissues from 34 patients and their correlation with chemotherapy resistance.. MDR1 and GST-pi expressions were analyzed by real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) and flow cytometry (FCM) at mRNA and protein levels, respectively. Chemotherapy sensitivity on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were detected by MTT assay.. The nonsensitive rates on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were 41.18%, 17.7%, 47.1%, 50.0%, 76.5%, 61.8% and 52.9%, respectively. The expression of P-glycoprotein (P-gp) and GST-pi in tumor tissues was 1.54 and 2.58 (relative fluorescence intensity). Chi2 analysis showed that there was a positive correlation between P-gp expression and drug resistance on ADM, GST-pi expression and resistance on ADM, DDP and MMC (P < 0.05). There was not seen obvious correlation between expression of MDR1, GST-pi and age, gender, pathological type, tumor size in osteosarcoma and soft tissue sarcoma patients (P > 0.05). The expression of GST-pi was increased in patients receiving preoperative chemotherapy. The rate of postoperative recurrence was higher in patients with higher GST-pi expression level than those with lower GST-pi expression level before operation (P < 0.05).. Individual differences exist in chemotherapy sensitivity and expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcomas patients. Chemotherapy can induce up-regulation of GST-pi protein expression. Primary high expression of GST-pi is the main mechanism of resistance of osteosarcoma and soft tissue sarcomas to chemotherapy and is related to poor prognosis.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; ATP Binding Cassette Transporter, Subfamily B, Member 1; Bone Neoplasms; Child; Cisplatin; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Flow Cytometry; Follow-Up Studies; Glutathione S-Transferase pi; Humans; Male; Middle Aged; Mitolactol; Mitomycins; Osteosarcoma; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sarcoma

A combined clinical and pharmacokinetic phase I study of the substituted hexitol dibromodulcitol (DBD), administered as a single oral monthly dose, has been performed. Twenty-three patients with advanced neoplasms received DBD doses ranging from 600 to 1,800 mg/m2 body surface area (BSA). The dose-limiting toxicity was myelosuppression, with both significant granulocytopenia and thrombocytopenia occurring at dose levels of 1,500 to 1,800 mg/m2. The average pharmacokinetic parameters for DBD, calculated on the basis of a one-compartment model with first-order absorption and elimination, include the elimination constant, .005 +/- .002/min; absorption constant, .012 +/- .009/min; and an apparent volume of distribution, 1.03 +/- .4 L/kg. The area under the drug concentration curve (AUC) and the peak drug level (Cmax) were linearly related to the dose administered (P less than .001). The mean AUC was 18.7 +/- 6.1 mmol/L min, and the mean Cmax was 47.1 +/- 16.8 mumol/L when normalized to a DBD dose of 1 gm/m2. The elimination constant was significantly reduced in patients with abnormal hepatic function (P less than .01). The elimination constant was not correlated with renal function. The half-life of DBD in plasma (158 minutes) was considerably shorter than the four-to eight-hour half-life of total radioactivity in plasma measured by previous investigators following the administration of radiolabeled DBD.

Topics: Absorption; Administration, Oral; Adult; Aged; Bone Marrow Transplantation; Carcinoma; Dianhydrogalactitol; Dose-Response Relationship, Drug; Drug Evaluation; Female; Half-Life; Humans; Kinetics; Male; Melanoma; Middle Aged; Mitolactol; Neoplasm Metastasis; Sarcoma; Time Factors

Patients with objectively measurable soft tissue sarcomas, osteosarcomas, chondrosarcomas, and mesotheliomas were treated with dibromodulcitol (DBD) (180 mg/m2 p.o. days 1-10 q4 wks.). ICRF-159 (300 mg/m2 p.o. tid days 1-3 q4 wks), or maytansine (MAYT) (1.5 mg/m2 I.V. q3 wks.). Forty-five evaluable patients received DBD, 47 MAYT, and 37 ICRF-159. Only patients who had had their histopathologic diagnoses confirmed by a pathology reference panel were included in the final analysis. Two patients had objective partial responses: a patient with osteosarcoma who responded to DBD and a patient with fibrosarcoma who had a partial response of brief duration to ICRF-159. Approximately 70% of the patients treated with each drug were of ECOG performance status 0 or 1, and over half had moderate or worse toxicity. It seems unlikely that these drugs have significant therapeutic activity for common mesenchymal malignancies.

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Drug Evaluation; Female; Humans; Male; Maytansine; Mesothelioma; Middle Aged; Mitolactol; Osteosarcoma; Oxazines; Piperazines; Prognosis; Random Allocation; Razoxane; Sarcoma; Soft Tissue Neoplasms

Adriamycin is a new anticancer antibiotic with a wide spectrum of activity against solid tumours. The results obtained with this agent in 159 patients with histologically confirmed advanced metastastic malignancies are reported. Encouraging results were obtained in patients with sarcomas of bone and soft tissue (12/22). Response was also seen in mesothelioma (3/9) and lung cancer (5/15). A variety of other neoplasms was also treated and results obtained in neuroblastoma, testicular tumours, stomach carcinoma, breast cancer and nephroblastoma are reported. Treatment is discussed, with reference to response rates and toxicity. Results in 72 patients with advanced breast cancer, who received adriamycin in combination with other chemotherapeutic agents, are presented. Seventeen patients with primary liver cancer were also treated with adriamycin. To date, this is the only chemotherapeutic agent that appears to significantly improve survival times in patients with this resistant form of cancer. The prophylactic use of adriamycin against osteogenic sarcoma is also discussed.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Infant; Liver Neoplasms; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Mitolactol; Neoplasm Metastasis; Neoplasms; Pleural Neoplasms; Sarcoma