Phase II study of induction chemotherapy with gemcitabine and vinorelbine followed by concurrent chemoradiotherapy with oral etoposide and cisplatin in patients with inoperable stage III non-small-cell lung cancer.
OBJECTIVE
For locoregionally advanced inoperable non-small-cell lung cancer (NSCLC), concurrent chemoradiotherapy has become a standard therapy. We conducted a Phase II trial to examine the efficacy and toxicity of adding gemcitabine and vinorelbine induction chemotherapy to concurrent chemoradiotherapy with oral etoposide and cisplatin.


METHODS
Eligibility included inoperable clinical Stage III NSCLC without pleural effusion, ECOG performance status 0-1, and weight loss < or =5%. Induction chemotherapy consisted of three cycles of gemcitabine 1,000 mg/m2 and vinorelbine 30 mg/m2, each given i.v. on Days 1 and 8, every 3 weeks. During once-daily thoracic radiotherapy (1.8 Gy/day, total 63 Gy), two cycles of oral etoposide (100 mg on Days 1-5 and 8-12) plus cisplatin (50 mg/m2 on Days 1 and 8) were given concurrently 4 weeks apart.


RESULTS
Between April 2002 and November 2003, 42 patients were enrolled and 40 were included in response and toxicity evaluation. The median age was 59 years and 13 patients had IIIA and 27 had IIIB; 24 had squamous ca, 12 had adenocarcinoma, and 4 had others. Objective tumor responses were obtained in 29 patients (72.5%), including 18 (45.0%) after induction chemotherapy. After a median follow-up of 23.8 months, the median survival time and progression-free survival was 23.2 months and 10.9 months, respectively, with 2-year survival rate of 43.9%. For the patients with supraclavicular nodal involvement, the median survival time was 11.8 months with 2-year survival rate of 16.7%, whereas the corresponding figures were 27.8 months and 52.0%, respectively, for those without supraclavicular nodal involvement. Toxicity of induction chemotherapy was mild and well tolerated. However, concurrent chemoradiotherapy was associated with G3/4 hematologic toxicity in 75.7%, G3 esophagitis in 24.2%, and two treatment-related deaths. There were nonlife-threatening late toxicities in additional 6 patients.


CONCLUSIONS
Induction chemotherapy with gemcitabine and vinorelbine followed by concurrent chemoradiotherapy with etoposide and cisplatin showed very promising survival in patients with Stage III NSCLC, especially in those without supraclavicular nodal involvement, which warrants further evaluation.
Lee
Dae Ho
DH
Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, South Korea.
Han
Ji-Youn
JY
Cho
Kwan Ho
KH
Pyo
Hong Ryull
HR
Kim
Hyae Young
HY
Yoon
Sung Jin
SJ
Lee
Jin Soo
JS
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D012074:Remission Induction; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D014747:Vinblastine; D005047:Etoposide; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine