Purpose Several recent trials have shown a significant overall survival (OS) benefit from postoperative cisplatin-based chemotherapy in patients with non–small-cell lung cancer (NSCLC). The aim of the Lung Adjuvant Cisplatin Evaluation was to identify treatment options associated with a higher benefit or groups of patients who particularly benefit from postoperative chemotherapy. Patients and Methods Individual patient data were collected and pooled from the five largest trials (4,584 patients) of cisplatin-based chemotherapy in completely resected patients that were conducted after the 1995 NSCLC meta-analysis. The interactions between patient subgroups or treatment types and chemotherapy effect on OS were analyzed using hazard ratios (HRs) and log-rank tests stratified by trial. Results With a median follow-up time of 5.2 years, the overall HR of death was 0.89 (95% CI, 0.82 to 0.96; P = .005), corresponding to a 5-year absolute benefit of 5.4% from chemotherapy. There was no heterogeneity of chemothera...

https://ascopubs.org/doi/pdf/10.1200/jco.2007.13.9030

Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group

background We undertook to determine whether adjuvant vinorelbine plus cisplatin prolongs overall survival among patients with completely resected early-stage non–small-cell lung cancer. methods We randomly assigned patients with completely resected stage IB or stage II non–smallcell lung cancer to vinorelbine plus cisplatin or to observation. The primary end point was overall survival; principal secondary end points were recurrence-free survival and the toxicity and safety of the regimen. results A total of 482 patients underwent randomization to vinorelbine plus cisplatin (242 patients) or observation (240); 45 percent of the patients had pathological stage IB disease and 55 percent had stage II, and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. In both groups, the median age was 61 years, 65 percent were men, and 53 percent had adenocarcinomas. Chemotherapy caused neutropenia in 88 percent of patients (including grade 3 febrile neutropenia in 7 percent) and death from toxic effects in two patients (0.8 percent). Nonhematologic toxic effects of chemotherapy were fatigue (81 percent of patients), nausea (80 percent), anorexia (55 percent), vomiting (48 percent), neuropathy (48 percent), and constipation (47 percent), but severe (grade 3 or greater) toxic effects were uncommon (<10 percent). Overall survival was significantly prolonged in the chemotherapy group as compared with the observation group (94 vs. 73 months; hazard ratio for death, 0.69; P=0.04), as was relapse-free survival (not reached vs. 46.7 months; hazard ratio for recurrence, 0.60; P<0.001). Five-year survival rates were 69 percent and 54 percent, respectively (P=0.03). conclusions Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non–small-cell lung cancer.

/pdf/vinorelbine-plus-cisplatin-vs-observation-in-resected-non-2igqmcr349.pdf

Vinorelbine plus Cisplatin vs. Observation in Resected Non–Small-Cell Lung Cancer

Summary Background Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer (NSCLC) is not known. We aimed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC. Methods 840 patients with stage IB–IIIA NSCLC from 101 centres in 14 countries were randomly assigned to observation (n=433) or to 30 mg/m 2 vinorelbine plus 100 mg/m 2 cisplatin (n=407). Postoperative radiotherapy was not mandatory and was undertaken according to every centre's policy. The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN95053737. Findings 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment. 301 (36%) patients had stage IB disease, 203 (24%) had stage II disease, and 325 (39%) had stage IIIA disease. Tolerance to chemotherapy mainly included neutropenia in 335 (92%) patients and febrile neutropenia in 34 (9%); seven (2%) toxic deaths were also recorded. Compliance was greater with cisplatin than with vinorelbine (median dose intensity 89% [range 17–108] vs 59% [17–100]). After a median follow-up of 76 months (range 43–116), median survival was 65·7 months (95% CI 47·9–88·5) in the chemotherapy group and 43·7 (35·7–52·3) months in the observation group. Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls (hazard ratio 0·80 [95% CI 0·66–0·96]; p=0·017). Overall survival at 5 years with chemotherapy improved by 8·6%, which was maintained at 7 years (8·4%). Interpretation Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC, better defining indication of adjuvant chemotherapy.

/pdf/adjuvant-vinorelbine-plus-cisplatin-versus-observation-in-40npjcp4ya.pdf

Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]) : a randomised controlled trial

Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

Non-small-cell lung cancer

Objectives: The non-small cell lung cancer (NSCLC) meta-analysis suggested a survival benefit for cisplatin-based chemotherapy when given in addition to surgery, radical radiotherapy or 'best supportive care'. However, it included many small trials and trials with differing eligibility criteria and chemotherapy regimens. The aim of the Big Lung Trial was therefore to run a large pragmatic trial to confirm the survival benefits seen in the meta-analysis. Methods: In the surgery setting, a total of 381 patients were randomised to chemotherapy (C, 192 patients) or no chemotherapy (NoC, 189 patients). C was three 3-weekly cycles of cisplatin/vindesine, mitomycin/ifosfamide/cisplatin, mitomycin/vinblastine/cisplatin or vinorelbine/cisplatin. Results: Chemotherapy was given before surgery in 3% of patients whilst 97% received adjuvant chemotherapy. Baseline characteristics were: median age 61 years, 69% male, 48% squamous cell, 93% WHO PS 0-1, 27% stage I, 38% stage II, and 34% stage III. Complete resection was achieved in approximately 95% of patients. In the C group, 13% received no chemotherapy, 21% one or two cycles, and 64% all three cycles of their prescribed chemotherapy (60% of the latter with no delays or modification). 30% had grade 3/4 toxicity, mainly haematological, nausea/vomiting and neutropenic fever, and six patients were reported as having a treatment-related death. 198 (52%) of patients have died, but there is currently no evidence of a benefit in overall survival to the C group: HR 1.02 (95% CI 0.77-1.35), P = 0.90). Conclusions: This trial has failed to observe a survival benefit with adjuvant chemotherapy following complete resection of stage I-III NSCLC. However, the hazard ratio and 95% confidence intervals are consistent with the previously reported meta-analysis and two large recently reported trials, which suggest a small survival benefit with cisplatin-based.

Rudd Rm

Papers

Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial.