Phase I trial of concurrent thoracic radiation and continuous infusion cisplatin and etoposide in stage III non-small cell lung cancer.
OBJECTIVE
Although combined modality therapy appears to be superior to radiotherapy alone for the treatment of locally advanced non-small cell lung cancer (NSCLC), the optimal treatment regimen has not been determined. We designed this trial to determine the maximal tolerated doses (MTD) of continuous intravenous infusion (CI) cisplatin and etoposide that could be administered concurrently with thoracic irradiation.


METHODS
19 patients with stage IIIA or IIIB NSCLC were treated at three different dose levels of CI cisplatin and etoposide with concurrent single daily fraction thoracic radiotherapy to 4500 cGy. This chemoradiotherapy phase of treatment was followed by a 1500-2000 cGy radiotherapy boost and three cycles of standard intermittent bolus cisplatin 80 mg/m2 i.v. on day 1 and etoposide 80 mg/m2 i.v. on days 1, 2 and 3.


RESULTS
The MTD of CI chemotherapy was determined to be cisplatin 5 mg/m2/day plus etoposide 18 mg/m2/day for 5 days per week over 5 weeks along with thoracic irradiation. Overall, 37% of patients required breaks in the chemoradiotherapy course and 32% required attenuation of the planned duration of CI chemotherapy. Only 42% of patients received all three planned cycles of bolus chemotherapy and 16% received < 6000 cGy of thoracic irradiation. The major toxicities during concurrent chemoradiotherapy were grade 3-4 esophagitis (42%) and myelosuppression (47%). Subsequent chemotherapy was complicated by grade 3-4 myelosuppression in 38% of patients. An objective response was documented in 58% of patients (CR 11%, PR 47%). Median survival was 18 months with 2- and 5-year survival rates of 42 and 11%, respectively.


CONCLUSIONS
These results demonstrate that CI cisplatin and etoposide can be administered safely to patients with locally advanced NSCLC, and that such potentially radiosensitizing strategies deserve further evaluation in this setting.
Kalemkerian
G P
GP
Department of Internal Medicine, Wayne State University and the Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA.
Belzer
K
K
Wozniak
A J
AJ
Gaspar
L E
LE
Valdivieso
M
M
Kraut
M J
MJ
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D015996:Survival Rate; D013909:Thorax / Q000528:radiation effects; D016896:Treatment Outcome
D005047:Etoposide; D002945:Cisplatin