Table 1 Clinical trials in cancer therapies related to IL-6, IL-8 and TGF-β signals
From: Cytokines, breast cancer stem cells (BCSCs) and chemoresistance
Compound and strategy | Cancer type | Phase | Description | Trial numbers | References |
|---|---|---|---|---|---|
Siltuximab; anti-IL-6 mAb | B-cell Non-Hodgkin’s lymphoma, multiple myeloma | Phase I | No dose-related or cumulative toxicity was apparent across all disease indications | NCT00412321 | [49] |
Siltuximab; anti-IL-6 mAb | Multiple myeloma | Phase II | Randomized study of bortezomib–melphalan–prednisone with or without siltuximab (anti-IL-6) in multiple myeloma | NCT00911859 | [50] |
Siltuximab; anti-IL-6 mAb | Multiple myeloma | Phase II | The safety and efficacy of siltuximab with or without dexamethasone for patients with relapsed or refractory multiple myeloma | N/A | [51] |
Siltuximab; anti-IL-6 mAb | Advanced solid tumors | Phase I/II | Siltuximab monotherapy appears to be well tolerated but without clinical activity in solid tumors | N/A | [52] |
Reparixin; CXCR1/2 antagonist | HER-2 negative metastatic breast cancer (MBC) | Phase Ib | Weekly paclitaxel plus reparixin in MBC appeared to be safe and tolerable | NCT02001974 | [53] |
Reparixin; CXCR1/2 antagonist | Early breast cancer | Phase II | Reparixin 1000Â mg t.i.d. for 21 consecutive days appeared to be well tolerated | NCT01861054 | [54] |
Galunisertib; TGFBR1 inhibitor | Advanced cancer and glioma | Phase I | Based on the safety, PK and antitumor activity in glioma patients, the intermittent administration of LY2157299 at 300Â mg/day is safe for future clinical investigation | N/A | |
Galunisertib; TGFBR1 inhibitor | Advanced hepatocellular carcinoma (HCC) | Phase II | HCC patients with normal AFP and with TGFβ1 reduction showed improvement in OS compared to patients with non-TGFβ1 reduction | NCT01246986 | [57] |
Galunisertib; TGFBR1 inhibitor | Recurrent glioblastoma | Phase II | Galunisertib + lomustine failed to demonstrate improved OS relative to placebo + lomustine | NCT01582269 | |
Galunisertib; TGFBR1 inhibitor | Advanced solid tumors | Phase I | Galunisertib had an acceptable tolerability and safety profile in Japanese patients with advanced cancers | NCT01722825 | [60] |
Galunisertib; TGFBR1 inhibitor | Pancreatic cancer | Phase II | GG (galunisertib + gemcitabine) resulted in improvement of OS and PFS in patients with PC, with a manageable toxicity profile as compared to GP (gemcitabine + placebo) | NCT01373164 | [61] |
PF-03446962; Anti-ALK1 mAb | Urothelial cancer | Phase II | They do not recommend further investigation outside of the combination with agents targeting the VEGF receptor axis | NCT01620970 | [62] |