A phase I study of weekly irinotecan (CPT), cisplatin (CIS) and flavopiridol (F)

4027 Background: F is a cyclin dependent kinase inhibitor which potentiates CPT- and CIS-induced apoptosis, with pathologic cures in colon cancer xenografts(Motwani, et.al. Clin Cancer Res 2001). We translated our preclinical studies into a phase I trial of CPT 100mg/m2 followed 7 hours later by F given over 1-hour weekly for 4 out of 6 weeks (Shah et al, ASCO 2003). To build on this, we have now performed a phase I trial of the combination of CPT, CIS and F. Methods: 26 patients (pts) have been enrolled: median age 54 (range 35–72), KPS 90%(80–90%), 1–2 prior regimens (0–4), and 17 males/7 females. The initial design was CPT 60 mg/m2 and escalating CIS (10 → 30mg/m2) administration, followed 7 hours later by F 50 mg/m2 given weekly for 3 weeks on, 1 week off. In cohort one (CIS 10 mg/m2), we noted dose limiting grade 3/4 neutropenia by week 3. In view of this, we changed the schedule to a 2 on, 1 off cycle. CIS dose escalation then successfully proceeded without dose limiting toxicity(DLT) until full cyt...