Improvements in quality of life and disease-related symptoms in phase I trials of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in non-small cell lung cancer and other solid tumors.
OBJECTIVE
The feasibility and utility of assessing quality of life (QoL) and disease-related symptoms in patients with advanced cancer have been evaluated in two Phase I clinical trials of p.o. administered ZD1839 ('Iressa'), an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced cancer.


METHODS
Functional Assessment of Cancer Therapy (FACT) questionnaires, including disease-specific subscales for lung, head and neck, colorectal, prostate, and ovarian cancer, were completed by patients in two open-label, Phase I, escalating multiple-dose safety and tolerability trials.


RESULTS
In 157 patients, 92% of whom had received prior therapy, compliance in returning FACT questionnaires was 87% (European/Australian trial) and 57% (United States trial). This did not appear to be influenced by dose level or tumor type. For patients with colorectal, prostate, or ovarian cancer, median QoL [FACT and Trial Outcome Index (TOI)] scores deteriorated over time. In contrast, for patients with non-small cell lung cancer (NSCLC) or head and neck cancer, median FACT and TOI scores did not deteriorate significantly, and in the United States trial, head and neck cancer scores improved significantly over time. In patients with NSCLC, symptom-related scores measured by the Lung Cancer Subscale of FACT-L appeared sensitive to clinical change.


CONCLUSIONS
QoL (FACT-L) questionnaires were used successfully in the Phase I clinical trials of ZD1839. They appeared to be a sensitive tool to monitor clinical changes for the five tumor types in these trials and showed that ZD1839 has the potential to improve patients' QoL.
LoRusso
Patricia M
PM
Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
Herbst
Roy S
RS
Rischin
Danny
D
Ranson
Malcolm
M
Calvert
Hilary
H
Raymond
Eric
E
Kieback
Dirk
D
Kaye
Stan
S
Gianni
Luca
L
Harris
Adrian
A
Bjork
Thomas
T
Maddox
Anne-Marie
AM
Rothenberg
Mace L
ML
Small
Eric J
EJ
Rubin
Eric H
EH
Feyereislova
Andrea
A
Heyes
Anne
A
Averbuch
Steven D
SD
Ochs
Judith
J
Baselga
José
J
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000523:psychology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011788:Quality of Life; D011799:Quinazolines / Q000009:adverse effects*
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib