Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 3554
© 2008 American Society of Clinical Oncology

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Abstract

Phase I safety and pharmacokinetic (PK) study of SU014813 (S) in combination with docetaxel (D) in patients (pts) with solid tumors (STs)

Universitaire Ziekenhuizen Leuven, Leuven, Belgium; Erasmus Medical Center, Rotterdam, The Netherlands; Pfizer S.R.L., Milan, Italy; Pfizer Global Research and Development, La Jolla, CA

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Background: S is an oral, multitargeted tyrosine kinase inhibitor (TKI) of PDGFRs, VEGFR-1 and -2, KIT and FLT3. This phase I study assessed the safety and PK of S in combination with D. Methods: Pts had refractory STs with ECOG PS 1. The first cohort received D 60 mg/m² IV every 3 wks (q3w) and continuous S 50 mg/d. Doses were escalated in serial cohorts of 3–6 pts to determine the maximum tolerated dose (MTD). The MTD was exceeded if >1/3 pts experienced dose limiting toxicities (DLTs) within the first 2 cycles (6 wks) of treatment. Adverse events (AEs) were graded according to NCI CTCAE v.3. Results: 23 pts (32–75 yrs) have been treated to date. All malignant melanoma (MEL) pts had progressed under DTIC/cisplatin ± other agents and all gastrointestinal stromal tumors (GISTs) were resistant to TKIs. All pts had progressive tumors at baseline according to RECIST. Doses ranged from 50–100 mg/d for S and 60–75 mg/m² for D. Most common tumor types were MEL (n=12), GIST (n=4), sarcoma (n=2) and cancer of unknown primary (CUP; n=2). Most frequent drug-related AEs were alopecia (70%), fatigue, nausea (65%), neutropenia, anorexia and diarrhea (60%). DLTs were observed in 3 pts at the highest doses and in 2/6 at MTD. Unacceptable toxicity, including neutropenic fever (n=5), asthenia (n=1) and neutropenia G4 (n=2), was also observed in 3 of 8 pts in an expanded cohort. Best responses according to RECIST included partial response (n=6, 1 of which unconfirmed), stable disease ([SD]; n=12), progressive disease (n=3) and too early (n=2). Of 12 pts with MEL, objective responses were observed in 4 pts. A further response was seen in CUP. Prolonged SD has been reported for 1 GIST pt who remains on treatment. The number of treatment cycles ranged from 1–22+ in the total population, 1–20+ in treatment-refractory MEL and 5–22+ in GIST. There was no evidence of a PK interaction between S and D based on maximum plasma concentrations and area under the curve. Conclusions: The combination of continuous S 50 mg/d with D 75 mg/m² q3w in pts with advanced STs is tolerable and active in treatment-refractory MEL, GIST and CUP. No PK drug interaction was observed. Further disease-specific phase II studies are clearly warranted at this dose.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer

Abstract presentation from the 2008 ASCO Annual Meeting