Sunitinib in combination with gemcitabine plus cisplatin for advanced non-small cell lung cancer: a phase I dose-escalation study.
OBJECTIVE
To determine the maximum tolerated dose (MTD) of sunitinib plus gemcitabine/cisplatin for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). Safety, pharmacokinetics, and antitumor activities were evaluated.


METHODS
Patients ≥18 years with Eastern Cooperative Oncology Group performance status 0/1 and stage IIIB/IV NSCLC were included in this open-label, multicenter, dose-escalation phase I study. Treatment was administered in 3-week cycles: oral sunitinib 37.5 or 50mg/day intermittently (Schedule 2/1: 2 weeks on treatment, 1 week off treatment) or 25mg continuous daily dosing (CDD) schedule with intravenous infusions of gemcitabine (1000 or 1250 mg/m(2) days 1, 8) and cisplatin (80 mg/m(2) day 1).


RESULTS
A total of 28 evaluable patients were assigned to four dose levels. Most adverse events (AEs) on the Schedule 2/1 MTD were mild to moderate. Dose delays due to myelosuppression occurred on both schedules, limiting treatment to a median of four cycles. Four of 18 evaluable patients (22%) on Schedule 2/1 and 1 of 6 patients (17%) on the CDD schedule had confirmed partial responses.


CONCLUSIONS
The MTD was identified as sunitinib 37.5mg (Schedule 2/1), gemcitabine 1250 mg/m(2), and cisplatin 80 mg/m(2), with most AEs being mild to moderate. However, frequent dose delays due to myelosuppression occurred. There was evidence of antitumor activity with this combination.
Reck
Martin
M
Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf 22927, Germany. dr.martin.reck@web.de
Frickhofen
Norbert
N
Cedres
Susana
S
Gatzemeier
Ulrich
U
Heigener
David
D
Fuhr
Heinz-Georg
HG
Thall
Aron
A
Lanzalone
Silvana
S
Stephenson
Patricia
P
Ruiz-Garcia
Ana
A
Chao
Richard
R
Felip
Enriqueta
E
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002985:Clinical Protocols; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000077210:Sunitinib; D000093542:Gemcitabine
D007211:Indoles; D011758:Pyrroles; D003841:Deoxycytidine; D002945:Cisplatin; D000077210:Sunitinib; D000093542:Gemcitabine