A Phase III Randomized Trial of Combined Chemoradiotherapy Versus Radiotherapy Alone in Locally Advanced Non–Small-Cell Lung Cancer

The Systemic Immune-Inflammation Index (SII) is an important marker of immune function, defined as the product of neutrophil-to-lymphocyte ratio (NLR) and platelet count (P). Higher baseline SII levels have been associated with improved survival in various types of cancers, including lung cancer. Data were obtained from PROCLAIM, a randomized phase III trial comparing two different chemotherapy regimens pemetrexed + cisplatin (PEM) vs. etoposide + cisplatin (ETO), in combination with radiotherapy (RT) for the treatment of stage III non-squamous non-small cell lung cancer (NSCLC). We aimed to determine if SII measured at the mid-treatment window for RT (weeks 3–4) is a significant predictor of survival, and if the effect of PEM vs. ETO differs by quartile (Q) level of SII. Hazard-ratios (HR) for survival were estimated using a proportional hazards model, accounting for the underlying correlated structure of the data. A total of 548 patients were included in our analysis. The median age at baseline was 59 years. Patients were followed for a median of 24 months. Adjusting for age, body mass index, sex, race, and chemotherapy regimen, SII was a significant mid-treatment predictor of both overall (adjusted HR (aHR) = 1.6, p < 0.0001; OS) and progression-free (aHR = 1.3, p = 0.0072; PFS) survival. Among patients with mid-RT SII values above the median (6.8), those receiving PEM (vs. ETO) had superior OS (p = 0.0002) and PFS (p = 0.0002). Our secondary analysis suggests that SII is an informative mid-treatment marker of OS and PFS in locally advanced non-squamous NSCLC.

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C6-01: Correlations of biomarker expression and clinical outcome in a large phase III trial of pemetrexed plus cisplatin or gemcitabine plus cisplatin in chemonaive patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)

Journal of Thoracic Oncology ◽

10.1097/01.jto.0000283223.48520.7c ◽

2007 ◽

Vol 2 (8) ◽

pp. S375 ◽

Cited By ~ 5

Author(s):

Giorgio Scagliotti ◽

Christopher Kaiser ◽

Bonne Biesma ◽

Christian Manegold ◽

Ulrich Gatzemeier ◽

...

Keyword(s):

Lung Cancer ◽

Clinical Outcome ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Locally Advanced ◽

Small Cell ◽

Phase Iii ◽

Small Cell Lung ◽

Phase Iii Trial ◽

Large Phase

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Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.4.1388 ◽

1998 ◽

Vol 16 (4) ◽

pp. 1388-1396 ◽

Cited By ~ 21

Author(s):

J P Sculier ◽

M Paesmans ◽

J Thiriaux ◽

J Lecomte ◽

G Bureau ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Randomized Trial ◽

Cell Lung Cancer ◽

Response Rate ◽

Objective Response ◽

Small Cell ◽

Phase Iii ◽

Small Cell Lung ◽

Moderate Dose

PURPOSE A phase III randomized trial in patients with advanced non-small-cell lung cancer (NSCLC) was performed to determine if the addition of ifosfamide to moderate-dose cisplatin and carboplatin improved response rate (primary end point) and survival. PATIENTS AND METHODS A total of 529 patients were randomized to receive a combination of moderate-dose carboplatin (200 mg/m2 intravenously [i.v.] on day 1) and cisplatin (30 mg/m2 i.v. on days 2 and 3) with (CCI arm) or without (CC arm) ifosfamide (1.5 g/m2 i.v. on days 1 to 3). There were 248 eligible patients on the CC arm and 257 on the CCI arm, with 220 and 238 patients assessable for response, respectively. All but 23 had stage IV disease with pleural effusion. RESULTS There was a 16% objective response (OR) rate to CC and a 31% OR rate to CCI. That observed difference was highly statistically significant (P < 0.001). Duration of response and survival were not statistically different between arms. The CCI regimen was associated with significantly more acute toxicities: emesis, alopecia, leukopenia, and thrombocytopenia. The frequency of chronic renal, auditive, and peripheral neurologic toxicity was low in both arms (4.6% and 6.6%, respectively, after six courses of chemotherapy). The relative dose-intensity (RDI) of the CCI arm was significantly lower than that of the CC arm. CONCLUSION The addition of ifosfamide to moderate-dose cisplatin and carboplatin significantly improves the antitumoral response rate, but has no apparent effect an survival in advanced NSCLC.

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