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PLoS One. 2014 Jul 10;9(7):e102436. doi: 10.1371/journal.pone.0102436. eCollection 2014.

Tocilizumab, a proposed therapy for the cachexia of Interleukin6-expressing lung cancer.

Author information

1
Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Bunkyo-Ku, Tokyo, Japan.
2
Department of Respiratory Internal Medicine, Kameda Medical Center, Kamogawa-City, Chiba, Japan.
3
Fukuoka Clinic, Adachi-Ku, Tokyo, Japan.
4
Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
5
Shien-lab, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
6
Department of Genome Biology, Kinki University Faculty of Medicine, Higashiosaka City, Osaka, Japan.

Abstract

BACKGROUND:

We previously reported the role of IL-6 in a murine model of cancer cachexia and currently documented a patient in whom tocilizumab, anti-IL-6 receptor antibody, dramatically improved cachexia induced by IL-6 over-expressing lung cancer. Despite this potential to alleviate cancer cachexia, tocilizumab has not been approved for this clinical use. Therefore, preceding our planned clinical trial of tocilizumab, we designed the two studies described here to evaluate the levels of IL-6 in patients with lung cancer and the effect of tocilizumab in a murine model of human cancer cachexia.

METHODS:

First, we measured serum IL-6 levels in patients with lung cancer and analyzed its association with cachexia and survival. Next, we examined the effect of a rodent analog of tocilizumab (MR16-1) in the experimental cachexia model.

RESULTS:

Serum IL-6 levels were higher in patients with cachexia than those without cachexia. In patients with chemotherapy-resistant lung cancer, a high IL-6 serum level correlated strongly with survival, and the cut-off level for affecting their prognosis was 21 pg/mL. Meanwhile, transplantation of IL-6-expressing Lewis Lung Carcinoma cells caused cachexia in mice, which then received either MR16-1 or 0.9% saline. Tumor growth was similar in both groups; however, the MR16-1 group lost less weight, maintained better food and water intake and had milder cachectic features in blood. MR16-1 also prolonged the survival of LLC-IL6 transplanted mice (36.6 vs. 28.5 days, p = 0.016).

CONCLUSION:

Our clinical and experimental studies revealed that serum IL-6 is a surrogate marker for evaluating cachexia and the prognosis of patients with chemotherapy resistant metastatic lung cancer and that tocilizumab has the potential of improving prognosis and ameliorating the cachexia that so devastates their quality of life. This outcome greatly encourages our clinical trials to evaluate the safety and efficacy of tocilizumab treatment for patients with increased serum IL-6.

PMID:
25010770
PMCID:
PMC4092149
DOI:
10.1371/journal.pone.0102436
[Indexed for MEDLINE]
Free PMC Article

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