Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma

Citation
Gk. Schwartz et al., Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma, J CL ONCOL, 19(7), 2000, pp. 1985-1992
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
JOURNAL OF CLINICAL ONCOLOGY
ISSN journal
0732-183X → ACNP
Volume
19
Issue
7
Year of publication
2000
Pages
1985 - 1992
Database
ISI
SICI code
0732-183X(20000401)19:7<1985:PISOTC>2.0.ZU;2-H
Abstract
Purpose: Flavopiridol is the first cyclin-dependent kinase inhibitor to ent er clinical trials. Activity in gastric cancer xenografts and in a patient with gastric cancer on the phase I trial led to this phase II study of flav opiridol in patients with metastatic: gastric cancer. Patients and Methods: Sixteen patients were entered onto the study, and 14 were assessable for response. Flavopiridol was administered initially at a dose of 50 mg/m(2)/d by continuous infusion for 72 hours every 2 weeks. Ass essment of plasma pharmacokinetics was performed in all patients. Periphera l mononuclear cells were collected throughout the 72-hour infusion for dete rminants of apoptosis. Results: There were no major objective responses (exact confidence interval 0% to 23%). One patient achieved a minor response in his liver metastases, though the primary progressed. Other patients exhibited histologic and rad iographic evidence of tumor necrosis, Common toxicities included fatigue in 93% of patients (grade 3 or 4 in 27%) and diarrhea in 73% of patients (gra de 3 or 4 in 20%). Five patients (33%) developed venous thromboses at the c entral catheter tip. The studies performed on peripheral mononuclear cells indicated no induction of apoptosis. Conclusion: Flavopiridol administered as a single agent for 72 hours every 14 days is inactive in the treatment of gastric cancer. The drug also induc ed an unexpected higher incidence of vascular thrombosis and fatigue than w as anticipated from the phase I trials. Future development of flavopiridol will depend on other doses and schedules in combination with chemotherapy. (C) 2001 by American Society of Clinical Oncology.