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  • 1
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Didemnin B (NSC 325319), a cyclic depsipeptide isolated from a Caribbean tunicate, exhibits potent preclinical antitumor activity. In previous phase I studies, 3.47 mg/m2 was the maximally tolerated dose, with nausea and vomiting being the dose-limiting toxicity. The drug was given in a single bolus infusion over 30 min every 28 days. In the current study, 30 patients presenting with previously treated non-small-cell lung cancer (NSCLC) received 46 courses of the drug at doses ranging from 3.47 to 9.1 mg/m2. Neuromuscular toxicity was dose-limiting. Neusea and vomiting appeared to be correlated with dose levels and were ameliorated by a combination of antiemetics including dexamethasone. Other side effects included a mild rise in hepatic enzymes and an allergic reaction that was preventable by the addition of corticosteroids to the premedication regimen. In all, 2 minor responses were seen among 24 evaluable patients. Because neuromuscular toxicity is dose-limiting, we recommend that routine measurements of creatine kinase and aldolase, a careful neurologic evaluation, and electromyography and muscle biopsy (if indicated) be incorporated into phase II trials. The recommended dose for phase II studies using a single bolus schedule is 6.3 mg/m2, following the premedication of patients with antiemetics.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Edatrexate (10-ethyl-10-deaza-aminopterin; CGP 30 694) is a methotrexate (MTX) analogue that shows promise against non-small-cell lung cancer (NSCLC) and other tumors. Since edatrexate's mechanism of action is the same as the saf MTX, we used leucovorin in an attempt to alleviate its dose-limiting toxicity, stomatitis. In four patients with NSCLC who had experienced significant stomatitis after treatment with edatrexate, cyclophosphamide, and cisplatin, we observed a remarkable reduction in stomatitis following the administration of lowdose leucovorin. On the basis of the results obtained in these individuals, we treated 15 additional patients with these iree-drug regimen plus leucovorin rescue. These subjects could tolerate the treatment with lesser degrees of stomatitis and received higher edatrexate doses in subsequent courses as compared with the patients who previously received this regimen without leucovorin rescue. This approach is expected to improve the therapeutic indices of edatrexate and edatrexate-containing chemotherapy regimens by modifying the dose-limiting toxicity of this antineoplastic agent.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-0646
    Keywords: mesothelioma ; dihydro-5-azacytidine ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-0646
    Keywords: non-small cell lung cancer ; chemotherapy ; 10-ethyl-10-deaza-aminopterin ; 10-EdAM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty-one patients with stage IIIB or IV non-small cell lung cancer (NSCLC) were treated with intravenous 10-EdAM on a weekly basis. The starting dose was 80 mg/m2, with subsequent doses adjusted depending on evidence of toxicity. There were 20 men and 11 women with a median age of 58 years (range, 33–75). Response was evaluated in 30 patients, 5 with evaluable but not measurable tumors and 25 with measurable indicator lesions. There were no complete remissions; 3 patients achieved partial remission. Nine patients had a minor response, 6 showed no change, and 12 had progressive disease. Median survival for all 31 patients was 43 weeks (range, 12–65+). During the first 3-week period, the 10-EdAM dose was reduced or withheld in 19 patients (because of stomatitis in 12, SGPT elevation in 3, skin rash in 2, and granulocytopenia in 2), escalated in 11 patients, and unchanged in 1 patient. A mean of 34–88 mg/m2of 10-EdAM (median, 50) was given per week during the first 5-week period. Myelotoxicity was infrequent and there was no significant nephrotoxicity. Considering the modest side effects of this treatment and the conservative dose-modification schedule which mandated substantial dose reductions, we conclude that 10-EdAM is a promising antitumor agent for NSCLC.
    Type of Medium: Electronic Resource
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