Phase II Trial of a Trimodality Regimen for Stage III Non–Small-Cell Lung Cancer Using Chemotherapy As Induction Treatment With Concurrent Hyperfractionated Chemoradiation With Carboplatin and Paclitaxel Followed by Subsequent Resection: A Single-Center Study

Abstract

PURPOSE We started a phase II trial of induction chemotherapy and concurrent hyperfractionated chemoradiotherapy followed by either surgery or boost chemoradiotherapy in patients with advanced, stage III disease. The purpose is to achieve better survival in the surgery group with minimum morbidity and mortality. PATIENTS AND METHODS Patients treated from 1998 to 2002 with neoadjuvant chemoradiotherapy and surgical resection for stage III NSCLC were analyzed. The treatment consisted of four cycles of induction chemotherapy with carboplatin/paclitaxel followed by chemoradiotherapy with a reduced dose of carboplatin/paclitaxel and accelerated hyperfractionated radiotherapy with 1.5 Gy twice daily up to 45 Gy. After restaging, operable patients underwent thoracotomy. Inoperable patients received chemoradiotherapy up to 63 Gy. Study end points included resectability, pathologic response, and survival. Results One hundred twenty patients were enrolled; 25% patients had stage IIIA, 73% had stage IIIB, and 2% stage IV. After treatment, 47.5% had downstaging, 29.2% had stable disease, and 23.3% had progressive disease. Thirty patients (25%) were not eligible for operation because of progressive disease, stable disease, and/or functional deterioration with one treatment-related death. The 30-day mortality was 5% in patients who underwent operation. The 5-year survival rate for 120 patients was 21.7%, and it was 43.1% in patients with complete resection. In postoperative patients with stage N0 disease, 5-year survival was 53.3%; if stage N2 or N3 disease was still present, 5-year survival was 33.3%. CONCLUSION Staging and treatment with chemoradiotherapy and complete resection performed in experienced centers achieve acceptable morbidity and mortality.

A phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapy before surgery in patients with pathologically confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903)

“…Conversely, grade 3/4 esophagitis has been recorded in 8% to 53% of patients where radiation was delivered in a hyperfractionated accelerated fashion. [9][10][11]17,18 More importantly, no treatment-related deaths were observed in either arm in our trial during the induction and postoperative periods. Lobectomies may be safely performed following induction therapy, whereas pneumonectomy, especially on the right, may carry an unacceptable rate of perioperative mortality.…”

Multimodality Treatment With Surgery for Locally Advanced Non–Small-Cell Lung Cancer With N2 Disease: A Review Article

“…[21][22][23][24][44][45][46][47][48][49][50] However, the results are inconsistent, and conclusive evidence has yet to be obtained. Table 1 shows the clinical outcomes of 6 representative phase II studies (1 study was phase I/II).…”

“…Six phase I/II or II studies included patients with stage IIIA disease who were preoperatively confirmed to harbor N2 disease or stage IIIB disease. [44][45][46][47][48][49] The patients were treated with induction therapy, including chemoradiation or chemotherapy, followed by surgical resection, and some studies added postoperative treatments, as shown in Table 1. A radiological response and pathological complete response were achieved in 48% to 73% and 5% to 17% of patients, respectively, and complete resection was achieved in 60% to 85% of cases.…”

Pathological Status of Mediastinal Lymph Nodes after Preoperative Concurrent Chemoradiotherapy Determines Prognosis in Patients with Non-Small Cell Lung Cancer

“…The results of surgical resection alone for locally advanced NSCLC are poor; thus the treatment option of induction chemoradiotherapy has been investigated. 1,2) Although there is consensus about the indication for a multimodality approach in most patients with locally advanced disease, there is no clear agreement about which local therapy should be applied in a given situation.…”