Predictive value of chemotherapy-induced neutropenia for the efficacy of oral fluoropyrimidine S-1 in advanced gastric carcinoma

Abstract

Myelosuppression that occurs during chemotherapy has been reported to be a predictor of better survival in patients with breast or lung carcinomas. We evaluated the prognostic implications of chemotherapy-induced neutropenia in advanced gastric carcinoma. Data from a prospective survey of oral fluoropyrimidine S-1 for advanced gastric cancer patients in Japan were reviewed. We identified 1055 untreated patients with adequate baseline bone marrow function. During treatment with S-1, a total of 293 (28%) patients experienced grade 1 or higher neutropenia. The adjusted hazard ratio of death for the presence of neutropenia, as compared with the absence of such toxicity, from a multivariate Cox model was 0.72 (95% confidence interval, 0.54 -0.95; P ¼ 0.0189) for grade 1 neutropenia, 0.63 (0.50 -0.78; Po0.0001) for grade 2 neutropenia and 0.71 (0.51 -0.98; P ¼ 0.0388) for grade 3 -4 neutropenia. These findings suggest that the occurrence of neutropenia during chemotherapy is an independent predictor of increased survival in patients with advanced gastric cancer, whereas the absence of such toxicity indicates that the dosages of drugs are not pharmacologically adequate. Monitoring of neutropenia in patients who receive chemotherapy may contribute to improved drug efficacy and favourable survival.

Chemotherapy-induced neutropenia as a prognostic factor in advanced non-small-cell lung cancer: results from Japan Multinational Trial Organization LC00-03

“…Furthermore, severe neutropenia (grade 3 -4) was no better than mild neutropenia (grade 1 -2) for prediction of overall survival. As a whole, these results are consistent with previous reports of the chemotherapy of NSCLC and gastric cancer (Di Maio et al, 2005;Yamanaka et al, 2007;Pallis et al, 2008), and strongly suggest that neutropenia per se is not important, but the use of neutropenia to reflect that an adequate dose has been given.…”

“…However, several studies in the last decade have reported that larger doses of chemotherapy do not always improve prognosis (Stadtmauer et al, 2000;Möbus et al, 2007). Using a unique time-dependent approach to analyse data from a prospective survey of patients with advanced gastric cancer treated with oral fluoropyrimidine S-1, Yamanaka et al (2007) reported that survival was longest in patients who experienced grade-2 neutropenia as the worst grade.…”

“…Pallis et al (2008) have also shown the association between chemotherapy-induced neutropenia and better clinical outcome for patients with NSCLC. In a prospective survey of oral fluoropyrimidine S-1 in 1055 patients with advanced gastric cancer, Yamanaka et al (2007) reported that patients with moderate (grade-2) neutropenia had the longest survival.…”

Impact of granulocyte colony–stimulating factors in metastatic colorectal cancer patients

“…A number of studies have also looked specifically at chemotherapy-induced neutropenia and survival. Studies in gastric, ovarian, breast, and lung cancers have all shown that survival was improved in patients who experienced neutropenia while on chemotherapy compared with patients who did not [31][32][33][34][35][36] .…”

Neutrophils in cancer: neutral no more

“…Interestingly, chemotherapy-induced neutropenia is associated with improved survival in patients with non-small cell lung, breast, gastric or colorectal cancer [182][183][184][185] . This beneficial association may be explained by two reasons, one of which is neutrophil-independent and the other neutrophil-dependent.…”