In other words, it may be hypothesized that patients with elevated baseline neutrophils are completely protected from any grade of chemotherapy-induced neutropenia and have a poorer prognosis, independently from chemotherapy dosing. Recently, the result of a large, multicenter, randomized trial of flat dosing versus intrapatient
dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer has been published [60]. A total of 964 patients were randomized. Dose escalation was achieved in 77% of patients who had ≥1 cycle. Intrapatient dose escalation of carboplatin based on nadir blood neutrophils or thrombocytes was feasible and http://www.selleckchem.com/mTOR.html safe. However, it provided no improvement in PFS or OS compared with flat dosing. Selleck INCB018424 In multivariate analysis, high baseline neutrophil counts had a significant adverse prognostic value whereas nadir neutrophils counts were not statistically significantly associated with outcome. The authors concluded that baseline neutrophils over-ride nadir counts in prognostic significance and questioned the use of dose escalation as a standard practice. The clinical relevance of tumor-infiltrating
neutrophils has recently begun to emerge. Direct associations between tumor-infiltrating neutrophils next and poor clinical outcome have now been described for
several types of human cancer. The prognostic role of tumor-infiltrating neutrophils, elevated blood neutrophils and elevated blood neutrophil/lymphocyte ratio has been associated with poor clinical outcome, most notably in renal cell carcinoma, melanoma, colorectal cancer, hepatocellular carcinoma, cholangiocarcinoma, glioblastoma, GIST, gastric, esophageal, lung, ovarian and head and neck cancer. A striking finding is the notion that high baseline neutrophil count in either tumor or blood, or both, was identified as a strong, independent risk factor for poor outcome and the negative prognostic impact of neutrophils was not eliminated by increasing the dose of cytokines, chemotherapy, or targeted therapy. For several cancers, patients benefit most from therapy if baseline neutrophil was low. Thus, baseline neutrophils over-ride nadir counts in prognostic significance. This has especially been shown in kidney cancer, colorectal cancer, non-small cell lung cancer, ovarian cancer and nasopharyngeal carcinoma.