In this study it was hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients. The study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population.
Selections of appropriate regimen of high-dose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: reargument of such contentious therapeutic preferences.
Background We hypothesized that combination of den- dritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemother- apy (HDC) would be effective for selected metastatic breast cancer (MBC) patients.
Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m2 docetaxel and 75 mg/m2 thiotepa versus 87 patients of HDC – DC/CIK: 120 mg/m2 docetaxel to mobilize peripheral CD34 – progenitor cells, a sequence of HDC (120 mg/m2 docetaxel, plus 175 mg/m2 thiotepa) – DC/CIK, with or without 400 mg/m2 carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS). Results Compared with SDC, PFS and
OS were improved in HDC – DC/CIK (median PFS 10.2 vs. 3.7 months,P \ 0.001; median OS 33.1 vs. 15.2 months, P \ 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed pro- longed PFS and OS. SDC group also achieved the similar response as previous reports.
Although this study could not be regarded as an entire prospective clinical trial, 166 patients in this comparative study were divided into HDC plus adoptive cellular therapy with DC/CIK cells or standard dose che-motherapy. While the complex nature of our treatment regimen will require additional studies to determine the role of each of the components, including autologous DC, CIK, and high-dose docetaxel and thiotepa, we have demonstrated the feasibility and tolerability of a thera- peutic regimen combining chemo plus immunotherapy. To our knowledge, it might be the first trial to combine all of the elements in the treatment of patients with MBC.
This study demonstrated the novel combina- tion of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.