Phase II randomized study of vandetanib plus gemcitabine or gemcitabine plus placebo as first-line treatment of advanced non-small-cell lung cancer in elderly patients.
BACKGROUND
The aim of the present study was to evaluate the efficacy and tolerability of vandetanib plus gemcitabine (V/G) compared with gemcitabine alone in elderly patients with untreated advanced non-small-cell lung cancer.


METHODS
This was a phase II, randomized, double-blind study. A total of 124 elderly patients (mean age, 75 yr; age range, 70-84 yr; 73% men) received V/G (n = 61) or placebo plus gemcitabine (n = 63). Progression-free survival (PFS) was the primary endpoint. Secondary endpoints were overall survival, objective response rate, duration of response, disease control rate, time to deterioration of performance status, and safety outcomes.


RESULTS
PFS was significantly prolonged with V/G (median, 183 days; 95% confidence interval, 116-214) compared with placebo plus gemcitabine (median, 169 days; 95% confidence interval, 95-194; p = 0.047). No statistically significant differences between arms were observed in all secondary endpoints, including overall survival. The addition of vandetanib to gemcitabine was well tolerated. The rate of patients with ≥1 treatment-related adverse event was comparable in the two arms, pyrexia, dyspnea, and neutropenia being the most common adverse events.


CONCLUSIONS
V/G combination was associated with a statistically significant prolongation of PFS compared with gemcitabine alone in untreated elderly patients with advanced non-small-cell lung cancer, with an acceptable safety profile.
*Division of Medical Oncology, "SG Moscati" Hospital, Avellino, Italy; †Department of Oncology, University of Turin, AOU San Luigi Orbassano, Turin, Italy; ‡Medical Oncology 1, "Fondazione IRCCS Istituto Nazionale dei Tumori", Milan, Italy; §Department of Oncology, San Paolo Hospital, Milan, Italy; ‖Second Medical Oncology Unit, "Istituto Oncologico Veneto", Padua, Italy; ¶European Institute of Oncology, Milan, Italy; #Department of Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola (FC), Italy; **Division of Medical Oncology, S. Maria della Misericordia Hospital, Perugia, Italy; ††Lung Cancer Unit, National Institute for Cancer Research, Genoa, Italy; ‡‡Medical Oncology Department, Santa Chiara Hospital, Trento, Italy; §§Medical Oncology Unit, San Vincenzo Hospital, Taormina, Catania, Italy; ‖‖Oncology Unit, Santa Maria delle Croci Hospital, Ravenna, Italy; ¶¶Medical Oncology Department, AUSL Bologna, Italy; ##Medical Oncology Unit, "Giovanni Paolo II" National Cancer Centre, Bari, Italy; ***Department of Oncology, Azienda Ospedaliera Treviglio, Treviglio (BG), Italy; †††Department of Oncology, University Hospital of Udine, Udine, Italy; ‡‡‡Department of Oncology, Ospedale Niguarda Ca' Granda, Milan, Italy; §§§AstraZeneca, Basiglio (MI), Italy; ‖‖‖LB Research, Cantù (CO), Italy; and ¶¶¶Medical Oncology, Second University of Naples, Naples, Italy.
Cesare
C
Gridelli
Silvia
S
Novello
Nicoletta
N
Zilembo
Andrea
A
Luciani
Adolfo Gino
AG
Favaretto
Filippo
F
De Marinis
Giovenzio
G
Genestreti
Lucio
L
Crinò
Francesco
F
Grossi
Orazio
O
Caffo
Francesco
F
Ferraù
Giorgio
G
Cruciani
Alba Ariela
AA
Brandes
Domenico
D
Galetta
Sandro
S
Barni
Gianpiero
G
Fasola
Giulio
G
Cerea
Silvia
S
Ferrari
Claudio
C
Iannacone
Fortunato
F
Ciardiello
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects; D010919:Placebos / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate; D000093542:Gemcitabine
D010880:Piperidines; D010919:Placebos; D011799:Quinazolines; D003841:Deoxycytidine; C452423:vandetanib; D000093542:Gemcitabine