A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone.
OBJECTIVE
To find the maximum tolerated dose (MTD) of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors.


METHODS
This was a Phase I study using cohort dose escalation of OSI-461 dosed orally twice daily in combination with mitoxantrone 12 mg/m(2) given on Day 1 of each 21-day cycle.


RESULTS
OSI-461 dose was escalated to 1,000 mg po bid. One patient experienced a dose-limiting toxicity (DLT). Three patients discontinued the study due to adverse events (AE). Two patients (10%) had a partial response, and ten patients (50%) had stable disease as best response.


CONCLUSIONS
The combination of OSI-461 and mitoxantrone was well tolerated. Dose escalation was stopped because of toxicities in a concurrent Phase I trial. The response rate seen in patients with prostate cancer was comparable to response rates seen in trials of mitoxantrone and prednisone alone, and further studies of the combination of OSI-461 and mitoxantrone were not pursued.
Resta
Lee P
LP
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, CRB1-1M59, Baltimore, MD 21231, USA.
Pili
Roberto
R
Eisenberger
Mario A
MA
Spitz
Avery
A
King
Serina
S
Porter
Jennifer
J
Franke
Amy
A
Boinpally
Ramesh
R
Carducci
Michael A
MA
Sweeney
Christopher J
CJ
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D009369:Neoplasms / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D013467:Sulindac / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013736:Testicular Neoplasms / Q000188:drug therapy; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
C439285:(5-fluoro-2-methyl-1-(4-pyridyl)methylene-3-(N-benzyl)-indene)-acetamide hydrochloride; D000970:Antineoplastic Agents; D013467:Sulindac; D008942:Mitoxantrone
Clin Lung Cancer. 2005 May;6(6):361-6
15943897
Am J Clin Oncol. 2006 Aug;29(4):395-8
16891869
N Engl J Med. 2004 Oct 7;351(15):1513-20
15470214
J Thorac Oncol. 2006 Mar;1(3):218-25
17409860
Cancer Res. 2000 Jul 1;60(13):3338-42
10910034
J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
10655437
J Thorac Oncol. 2006 Sep;1(7):673-8
17409935
N Engl J Med. 2004 Oct 7;351(15):1502-12
15470213
BJU Int. 2005 May;95(7):963-8
15839914
J Clin Oncol. 2008 Mar 1;26(7):1148-59
18309951