Phase I/II trial of hyperfractionated radiation and chemotherapy followed by surgery in stage III lung cancer.
BACKGROUND
We have previously demonstrated that high-dose chemoradiotherapy followed by resection for patients selected on the basis of mediastinal sterilization was feasible and resulted in excellent outcomes. This study was designed to determine the ability to intensify our prior approach utilizing hyperfractionated radiation and more aggressive consolidative chemotherapy.


METHODS
Patients with documented stage IIIA/B nonsmall-cell lung cancer, performance status 0 to 2, and adequate organ function were eligible. A phase I portion utilized escalating doses of carboplatin and vinorelbine, commencing with areas under the curve of 1 and 5 mg/m(2), respectively, and concurrent 69.6 Gy hyperfractionated radiotherapy. A phase II portion utilized the identical radiotherapy with carboplatin/vinorelbine at the maximum tolerated dose established in phase I. Patients for whom mediastinal nodal clearance was demonstrated underwent resection. All patients were to receive consolidation chemotherapy consisting of carboplatin/vinorelbine for three cycles, followed by docetaxel for three cycles. Prophylactic cranial irradiation was offered to patients after completion of therapy.


RESULTS
Forty-seven patients participated in the study (33 IIIA, 14 IIIB; 15 men, 32 women; median age, 56 years). The maximum tolerated dose for concurrent carboplatin/vinorelbine and hyperfractionated radiotherapy was established at areas under the curve of 1 and 10 mg/m(2), respectively. Twenty-eight patients completed trimodality treatment including surgery. Median survival time for the entire study cohort (n = 47) is 29.6 months, and it is 55.8 months for patients with mediastinal clearance who underwent resection (n = 28).


CONCLUSIONS
Surgical resection of locally advanced stage IIIA and IIIB nonsmall-cell lung cancer after induction hyperfractionated radiation and concurrent chemotherapy is safe and well tolerated. Whether this approach is superior to less aggressive therapy is uncertain and will require comparative studies.
Edelman
Martin J
MJ
Division of Medical Oncology, University of Maryland School of Medicine and University of Maryland Greenebaum Cancer Center, Baltimore, Maryland 21201, USA. medelman@umm.edu
Suntharalingam
Mohan
M
Burrows
Whitney
W
Kwong
King F
KF
Mitra
Neha
N
Gamliel
Ziv
Z
Riley
Michelle
M
Cooper
Lindsay B
LB
Kennedy
Nancy L
NL
Buskirk
Susan
S
Hausner
Petr
P
Doyle
L Austin
LA
Krasna
Mark J
MJ
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D014747:Vinblastine; D016190:Carboplatin; D000077235:Vinorelbine