Impact of baseline and nadir neutrophil index in non-small cell lung cancer and ovarian cancer patients: Assessment of chemotherapy for resolution of unfavourable neutrophilia

Abstract

Background: Chronic inflammation has been recognized to foster tumour development. Whether chemotherapy can be used to neutralize chronic inflammation is unclear.

Methods: We evaluated baseline and nadir neutrophils in 111 patients (pts.) with non-small cell lung cancer (NSCLC) and 118 pts. with ovarian cancer (OC) treated with chemotherapy administered with dose-individualization to achieve nadir neutropenia of 1.5. We used predefined baseline neutrophil cut-offs 4.5 × 109/L (NSCLC) and 3.9 × 109/L (OC).

Results: Absence of chemotherapy-induced nadir neutropenia (CTCAE grade 0, neutrophils ≥ LLN) was seen in 23% of OC and 25% of NSCLC pts. Absence of nadir neutropenia was associated with decreased overall survival (OS) compared with presence (>grade 0) of neutropenia (9 vs. 14 months, P=0.004 for NSCLC and 23 vs. 56 months; P=0.01 for OC). Obtaining grade 3/4 neutropenia did not improve survival compared with grade 1/2 neutropenia. In multivariate analyses, baseline neutrophils ≥ 4.5 × 109/L (HR: 2.0; 95% CI: 1.11-3.44;P = 0.02) and absence of nadir neutropenia (HR: 1.6; 95% CI: 1.02-2.65;P = 0.04) for NSCLC and absence of nadir neutropenia (HR: 1.7; 95% CI: 1.04;2.93;P = 0.04) for OC were independently associated with short OS.

Conclusions: A neutrophil index comprising elevated baseline neutrophils and absence of neutropenia identified a high risk group of NSCLC and ovarian cancer patients with only modest effect of chemotherapy. New treatment options for this subset of patients are required.

Figure 1

Kaplan-Meier plot of overall survival for NSCLC patients (A) (N = 111) and ovarian cancer patients (B) (N = 118) stratified for neutropenia grade at nadir. Grade 0, neutrophils ≥ LLN; grade 1, neutrophils < LLN to 1.5 × 10⁹/L; grade 2, <1.5 - 1.0 × 10⁹/L; grade 3, <1.0 – 0.5 × 10⁹/L; grade 4, < 0.5 × 10⁹/L. P-values obtained from log-rank test.

Figure 2

Kaplan-Meier plot of overall survival for NSCLC patients (A) (N = 111) and ovarian cancer patients (B) (N = 118) stratified for favourable neutrophil index (NI) (low baseline neutrophils and presence of nadir neutropenia), intermediate neutrophil index (elevated baseline neutrophils and presence of nadir neutropenia), and poor neutrophil index (elevated baseline neutrophils and absence of nadir neutropenia) prognostic group. A fourth group with low baseline neutrophils and absence of nadir neutropenia comprised only 4 patients with ovarian cancer and no NSCLC, and was not classified.