Intensified high-dose chemoradiotherapy with induction chemotherapy in patients with locally advanced non-small-cell lung cancer-safety and toxicity results within a prospective trial.
OBJECTIVE
To analyze the toxicity profile of an intensified definitive chemoradiotherapy (CRT) schedule in patients with locally advanced non-small-cell lung cancer (Stage IIIA N2/selected IIIB) treated within a prospective multicenter trial.


METHODS
After mediastinoscopy and routine staging procedures, three cycles of induction chemotherapy (cisplatin 50 mg/m(2), Days 1 and 8; paclitaxel 175 mg/m(2) Day 1, every 21 days) were planned, followed by concurrent CRT (accelerated-hyperfractionated regimen, 45 Gy, 2 x 1.5 Gy/d, cisplatin 50 mg/m(2), Days 64 and 71, vinorelbine 20 mg/m(2), Days 64 and 71). At 45 Gy, a multidisciplinary panel decision was made regarding operability. Inoperable patients received definitive radiotherapy (total dose 65 or 71 Gy, depending on the mean lung dose) with additional concurrent chemotherapy (cisplatin 40 mg/m(2), Day 85; vinorelbine 15 mg/m(2), Days 85 and 92).


RESULTS
A total of 28 patients (23 men and 5 women; median age, 58 years; range 41-73; Stage IIIA in 3 and Stage IIIB in 25) were judged ineligible for surgery by the multidisciplinary panel and underwent definitive CRT (75% of the patients received 71 Gy). The maximum toxicity (Grade 3 or greater) during induction chemotherapy included leukopenia (11%) and anemia (4%). During concurrent CRT, leukopenia (Grade 3 or greater) was observed in 39% of the patients. The maximal nonhematologic toxicity during concurrent CRT included esophagitis (Grade 3 or greater) in 18% and pneumonitis (Grade 3 or greater) in 4% of the patients. At 3 years, the locoregional control rate was 52% (95% confidence interval, 29-75%) and the overall survival rate was 31% (95% confidence interval, 12-50%).


CONCLUSIONS
This intensified treatment protocol with induction chemotherapy and concurrent CRT, including hyperfractionated-accelerated RT, showed only moderate toxicity and proved feasible. This treatment represents the definitive CRT arm of our ongoing multicenter randomized trial comparing definitive CRT and trimodality treatment.
Pöttgen
Christoph
C
Department of Radiotherapy, University of Duisburg-Essen, Essen, Germany. christoph.poettgen@uk-essen.de
Eberhardt
Wilfried E
WE
Gauler
Thomas
T
Krbek
Thomas
T
Berkovic
Katharina
K
Jawad
Jehad Abu
JA
Korfee
Soenke
S
Teschler
Helmut
H
Stamatis
Georgios
G
Stuschke
Martin
M
D000328:Adult; D000368:Aged; D000740:Anemia / Q000209:etiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D004941:Esophagitis / Q000209:etiology; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000209:etiology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011014:Pneumonia / Q000209:etiology; D011446:Prospective Studies; D012074:Remission Induction / Q000379:methods; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
D014747:Vinblastine; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine