Feasibility study of two schedules of sunitinib in combination with pemetrexed in patients with advanced solid tumors.
BACKGROUND
Sunitinib is an oral multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors, as well as of other receptor types. We have performed a feasibility study to investigate the safety of sunitinib in combination with pemetrexed for treatment of advanced refractory solid tumors.


METHODS
Sunitinib was administered once daily on a continuous daily dosing (CDD) schedule (37.5 mg/day) or a 2-weeks-on, 1-week-off treatment schedule (50 mg/day, Schedule 2/1) in combination with pemetrexed at 500 mg/m(2) on day 1 of repeated 21-day cycles.


RESULTS
Twelve patients were enrolled in the study: six on the CDD schedule and six on Schedule 2/1. None of the treated patients experienced a dose-limiting toxicity. Toxicities were manageable and similar in type to those observed in monotherapy studies of sunitinib and pemetrexed. Pharmacokinetic analysis did not reveal any substantial drug-drug interaction. One patient with squamous cell lung cancer showed a partial response and five patients had stable disease.


CONCLUSIONS
Combination therapy with sunitinib administered on Schedule 2/1 (50 mg/day) or a CDD schedule (37.5 mg/day) together with standard-dose pemetrexed (500 mg/m(2)) was well tolerated in previously treated patients with advanced solid tumors.
Okamoto
Isamu
I
Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan. chi-okamoto@dotd.med.kindai.ac.jp
Shimizu
Toshio
T
Miyazaki
Masaki
M
Tsurutani
Junji
J
Ichikawa
Yasuko
Y
Terashima
Masaki
M
Takeda
Masayuki
M
Fumita
Soichi
S
Ohki
Emiko
E
Kimura
Nobuyuki
N
Hashimoto
Junichi
J
Nakagawa
Kazuhiko
K
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007564:Japan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000068437:Pemetrexed; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D000077210:Sunitinib; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D005971:Glutamates; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000068437:Pemetrexed; D006147:Guanine; D000077210:Sunitinib