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

Response rate with DCT

Response rate with DCTs

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Summary

This study analyzes the combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) and its effectiveness for selected metastatic breast cancer (MBC) patients. The study demonstrated the combination of HDC with DC/CIK to be an effective choice for MBC patients. Specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.

Introduction

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.

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.

Methodology

POur 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.

Treatment

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.

Results

•  P53 specific T cell response to vaccination were observed in 57.1% of all the patients

• A detectable preimmunization level of anti-p53 antibody was observed in 10 out of 22 (45%) and only 3 patients showed a significant increase in the level of anti-p53 antibodies after immunization.
• Adverse events associated with the administration of the vaccine were infrequent and mostly mild; 2 patients had grade 2 adverse events (1 with fatigue, 1 with arthralgia)
• 1 patient achieved partial response (PR), 7 patients achieved stable disease (SD) and 21 patients had progressive disease (PD)
• 1 patient with solid measurements revealed a 60% decreased in the size of all of her measurable lesions.
• The median overall survival of all the patients was 11.8 months from the time of the first vaccine administered.

Conclusion

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 chemotherapy. 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.

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Scientific article publishing date : 3/1/2013

Immucura identifier : BSC21_021EN

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