Primary chemotherapy for newly diagnosed nonsmall cell lung cancer patients with synchronous brain metastases compared with whole-brain radiotherapy administered first : result of a randomized pilot study.
BACKGROUND
This randomized pilot trial investigated whether primary chemotherapy was feasible in terms of efficacy, survival, toxicity profile, and quality of life compared with whole-brain radiotherapy (WBRT) given first in chemotherapy-naive patients nonsmall cell lung cancer (NSCLC) with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled by supportive care.


METHODS
After stratification by Eastern Cooperative Oncology Group performance status (ECOG PS) (0-1 vs 2), the number of intracranial metastases (<3 vs 3< or =), and the presence of extrathoracic extracranial metastasis, eligible patients were randomized to the primary chemotherapy arm or the WBRT-first arm. World Health Organization (WHO) response criteria, National Cancer Institute Common Toxicity Criteria (NCI-CTC; version 2.0), and the European Organization for Research and Treatment of Cancer (EORTC) C-30/LC-13 questionnaire were used.


RESULTS
A total of 48 patients were enrolled between August 2002 and November 2005. The response rate of chemotherapy and survival outcomes in the primary chemotherapy arm were not statistically different from those in the WBRT-first arm (overall response rate, 28.0% vs 39.1%; progression-free survival, 3.6 months vs 4.4 months; overall survival, 9.1 months vs 9.9 months). There was close correlation noted between intracranial and extracranial tumor responses (k = 0.82). However, in the WBRT-first arm, grade 3 of 4 neutropenia was more frequent (79% vs 40%) during chemotherapy and 4 patients (17.4%) did not receive further chemotherapy because of early death or poor performance after WBRT. Cognitive function appeared to deteriorate during primary chemotherapy, but was also found to deteriorate after WBRT.


CONCLUSIONS
Primary chemotherapy is more feasible and can be an appropriate option for patients with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled. The role and timing of WBRT should be defined in further studies in this clinical setting.
Lee
Dae Ho
DH
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea. jslee@ncc.re.kr
Han
Ji-Youn
JY
Kim
Heung Tae
HT
Yoon
Sung Jin
SJ
Pyo
Hong Ryull
HR
Cho
Kwan Ho
KH
Shin
Sang-Hoon
SH
Yoo
Heon
H
Lee
Seung-Hoon
SH
Lee
Jin Soo
JS
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011788:Quality of Life; D016019:Survival Analysis