Surgery With or Without Preoperative Paclitaxel and Carboplatin in Early-Stage Non–Small-Cell Lung Cancer: Southwest Oncology Group Trial S9900, an Intergroup, Randomized, Phase III Trial

Abstract

A B S T R A C T PurposePatients with early-stage non-small-cell lung cancer (NSCLC) have a poor prognosis even after complete resection. Earlier studies of preoperative (induction) chemotherapy in resectable NSCLC demonstrated feasibility and encouraging survival data. This randomized phase III trial compared overall survival (OS) for preoperative paclitaxel and carboplatin followed by surgery with surgery alone in patients with early-stage NSCLC. Patients and MethodsPatients with clinical stage IB-IIIA NSCLC (excluding superior sulcus tumors and N2 disease) were eligible. Patients were randomly assigned to surgery alone or to three cycles of paclitaxel (225 mg/m 2 ) and carboplatin (area under curve, 6) followed by surgical resection. The primary end point was OS; secondary end points were progression-free survival (PFS), chemotherapy response, and toxicity. ResultsThe trial closed early with 354 patients after reports of a survival benefit for postoperative chemotherapy in other studies. The median OS was 41 months in the surgery-only arm and 62 months in the preoperative chemotherapy arm (hazard ratio, 0.79; 95% CI, 0.60 to 1.06; P ϭ .11.) The median PFS was 20 months for surgery alone and 33 months for preoperative chemotherapy (hazard ratio, 0.80; 95% CI, 0.61 to 1.04; P ϭ .10.) Major response to chemotherapy was seen in 41% of patients; no unexpected toxicity was observed. ConclusionThis trial closed prematurely after compelling evidence supporting postoperative chemotherapy emerged. Although OS and PFS were higher with preoperative chemotherapy, the differences did not reach statistical significance. At present, stronger evidence exists for postoperative chemotherapy in early-stage NSCLC.

Video-Assisted Thoracic Surgery (VATS) Systematic Mediastinal Nodal Dissection

“…The first approach is advocated by Albain et al (2009) who showed that lobectomy will add little to Chemo-radiotherapy for patients with stage IIIa (N2) non-small-cell lung cancer, at the expense of higher mortality (evidence level 1b) [20]. The second approach is supported by the S9900 trial follow up published in 2010 which continues to show that the best treatment for N2 resectable lung cancer would be induction chemotherapy followed by surgery (evidence level 1b) [21]. Rocco et al (2010) is supportive of the third approach, concluding that standard treatment of initially resectable stage IIIa NSCLC remains surgery followed by adjuvant chemotherapy (evidence level 2a) [22].…”

Video-Assisted Thoracic Surgery Major Pulmonary Resections

“…The controversy arises in operable early cancer in the presence of a histologically proven single station mediastinal node (cT1-3, N2). The current best practice evidence supported by the S9900 trial follow up published in 2010 continues to show that the best treatment for N2 resectable lung cancer would be induction chemotherapy followed by surgery (evidence level 1b) [19]. Multizonal lung cancer is thought to be a systemic disease beyond cure by surgery alone, and is best treated by chemo-radiotherapy.…”

Rola systemowych metod leczenia u chorych na niedrobnokomórkowego raka płuca i złośliwego międzybłoniaka opłucnej: Uaktualnione zalecenia ekspertów

“…Przedoperacyjna (indukcyjna) chemioterapia była przedmiotem kilku badań III fazy, których wyniki były rozbieżne [27][28][29][30][31][32]. W większości badań obserwowano względnie wysoki odsetek obiektywnych odpowiedzi, a w kilku -także wydłużenie czasu przeżycia wolnego od nawrotu lub czasu całkowitego przeżycia.…”