A phase i-ii study of maytansine utilizing a weekly schedule

✍ Scribed by Roman Franklin; Michael K. Samson; Roberto J. Fraile; Hakam Abu-Zahra; Robert O'bryan; Laurence H. Baker

• Publisher: John Wiley and Sons
• Year: 1980
• Tongue: English
• Weight: 428 KB
• Volume: 46
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/1097-0142(19800901)46:5<1104::aid-cncr2820460505>3.0.co;2-t

✦ Synopsis

Maytansine, a new ansa macrolide antitumor antibiotic, was administered to a total of 107 patients in a Phase 1-11 study. Dose-limiting toxic reactions which occurred at 0.75-1.0 mg/M' in both Phase I and I1 were neurologic and consisted primarily of lethargylweakness (a debilitation syndrome) and paresthesias. Gastrointestinal and neurologic toxic reactions increased in frequency and severity as a function of dose. Myelosuppression, while infrequent, occurred only in previously treated patients. Changes in liver function tests were subclinical. Two partial remissions were observed at a dose-level of 0.5 mg/M2 in Phase I: 1 patient with squamous cell carcinoma of the lung responded for five weeks, while the other patient with adenocarcinoma of the lung responded for four weeks. One partial remission, lasting 14 weeks was seen in Phase I1 in a patient with malignant melanoma treated at a dose-level of 1.0 mg/M2. All responses were in heavily pretreated patients. Pairs of small bowel biopsy specimen used to define the mitotic index demonstrated peak mitotic arrest at 24 hours in contrast to vinca alkaloids which appear to have a peak mitotic arrest at 12-24 hours.