mitolactol and Bone-Neoplasms

The aim of this study was to compare the treatment efficacy of mitomycin-C plus tamoxifen (MT) to adriamycin, dibromodulcitol and tamoxifen (DAT) in previously treated patients with metastatic breast cancer. Thirty-two patients with measurable or evaluable disease were entered on the study. Twenty-three were prospectively randomized to receive DAT (Group 1) or MT (Group 2). Nine patients with prior exposure to adriamycin were directly assigned to receive MT (Group 3). Thirty-one patients were evaluable for response and toxicity. The hematological toxicities were comparable among the three treatment groups. DAT gave more nausea and vomiting than MT. One patient developed irreversible fatal congestive heart failure while receiving DAT. The response for Group 1 was 5/11, Group 2, 3/12, and Group 3, 3/8. The duration of response for patients in Group 1 was 455+, 315, 251, 239, 231 days, in Group 2 it was 328+, 144+, 119, and in Group 3 it was 35+, 84, and 112 days. The median time to treatment failure did not differ significantly between Group 1 (114 days), 2 (83 days) and 3 (61 days) (p = 0.24). The median survival time was similar among the three groups (p = 0.41). This pilot study suggests that MT and DAT are both effective treatment programs in patients with metastatic breast cancer who have failed prior chemotherapy regimens.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Doxorubicin; Drug Therapy, Combination; Female; Humans; Mitolactol; Mitomycin; Mitomycins; Pilot Projects; Random Allocation; Soft Tissue Neoplasms; Tamoxifen

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

Twenty-six evaluable patients with metastatic breast carcinoma previously treated with a combination of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) were treated with a combination of doxorubicin (Adriamycin), dibromodulcitol, and mitomycin (ADM). Four patients (15%) achieved complete remission, and 10 patients (39%) had a partial response. Five patients (19%) had stable disease, and seven patients (27%) experienced disease progression. The median time to disease progression was 10 months for responding patients (range, 4-44 months) and 5 months (range, 2-13 months) for patients with stable disease. The median survival duration was 15 months (range, 6-44+ months) for responders, 11 months (range, 2-27 months) for patients with stable disease, and 4 months (range, 2-41 months) for nonresponders. Two of the four patients with complete remission are alive and in continued remission at a follow-up of 44 and 40 months. Seventy-one patients with greater than or equal to two sites of metastasis responded, whereas 23% of patients with greater than or equal to three metastatic sites responded. Although higher responses were seen with soft tissue and osseous metastasis, responses were observed in all three sites of metastasis. This combination chemotherapy regimen with ADM is an effective second-line program for patients who have previously received CMFVP chemotherapy.

Topics: Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Leukopenia; Methotrexate; Middle Aged; Mitolactol; Mitomycins; Nausea; Prednisone; Soft Tissue Neoplasms; Thrombocytopenia; Time Factors; Vincristine; Vomiting

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

Co-operative investigation of clinical therapy for cancer is used to test hypotheses developed in single institutions and in animal research laboratories. The present studies in a large co-operative organization, the Central Oncology Group, are being conducted in seven major solid tumors in adults; in these studies patients with a poor surgical prognosis are being treated with preoperative or postoperative chemotherapy, preoperative radiotion therapy of these modalities. Results of studies currently underway or recently completed in 1,278 patients are summarized. In most instances, the research has demonstrated little or no apparent improvement in the disease free interval or the survival time from adjuvant therapy, although only on of the studies has been completed and fully evaluated thus far. In carcinoma of the colon and rectum and melanoma, mild toxicity from drug therapy has been associated with statistically significant improvement in survival times. These studies have produced base line information on disease free intervals, time to progression and survival time in patients with cancer who are seen in the participating institutions. These observations are expected to useful in the planning of future adjuvant studies.

Topics: Adult; Altretamine; Antineoplastic Agents; Bone Neoplasms; Breast Neoplasms; Carmustine; Colonic Neoplasms; Cyclophosphamide; Dacarbazine; Doxorubicin; Drug Evaluation; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Lomustine; Lung Neoplasms; Male; Melanoma; Mitolactol; Neoplasms; Osteosarcoma; Pancreatic Neoplasms; Rectal Neoplasms; Vincristine