mitolactol and Mesothelioma

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

In parallel to the clinical study CMEA 0102 and an experimental study with animal models the effectivity of carminomycin (CRM) in combination with dibromodulcitol (DBD) was tested on human mesothelioma cells in vitro. The cytostatic effect was evaluated by means of 3H-thymidine incorporation into DNA compared to controls. The used mesothelioma cells are more sensitive to CRM than to DBD in relation to their effective drug concentrations. 1.2 x 10(18) mol/l CRM inhibited 3H-thymidine incorporation to 30.6% +/- 9.3 and 3.9 x 10(-6) mol/l DBD to 35.3% +/- 18.3%. In 14/27 experiments the combination of CRM plus DBD in these low concentrations increased effectivity more than the summarized inhibition value, caused by single applied agents in vitro. However, the statistical evaluation of all results didn't confirm these observations. Alternating addition of the second antineoplastic agent three hours after the first did not result in additional effectivity compared to simultaneous one.

Topics: Carubicin; Cells, Cultured; Daunorubicin; Drug Therapy, Combination; Humans; Mesothelioma; Mitolactol; Thymidine

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