Table 3.
Key anti-inflammatory agents tested in clinical trials in cancer
| Agent/target | Tumor type | Combination regime | Key clinical trial | Reported action |
|---|---|---|---|---|
| Celecoxib | ||||
| COX-2 | Breast cancer | Neoadjuvant celecoxib + chemotherapy/cholecalciferol/exemestane | NCT02429427, NCT01041781 | Celecoxib induced favorable changes in serum biomarkers and cytology in women with increased risk for breast cancer, but demonstrated no significant benefits for patients with ERBB2-negative breast cancer |
| Lung cancer | Celecoxib + chemotherapy/RT/anti-EGFR TKIs | NCT00300729, NCT01503385 | Celecoxib at a maximal tolerated dose of 800 mg/d can be safely administered concurrently with thoracic radiotherapy of NSCLC | |
| CRC | Celecoxib + cetuximab/chemotherapy (FOLFIRI regimen)/RT/ | NCT03645187, NCT00005094, NCT00141193, NCT03926338, NCT01150045 | Celecoxib combined with chemotherapy (FOLFIRI regimen consisting of 5-flourouracil, leucovorin, irinotecan) or PD-1 blockade toripalimab represents an effective and safe synergetic protocol for patients with metastatic CRC | |
| Antiviral therapies | ||||
| Entecavir | ||||
| HBV | HCC | NCT00388674 | Entecavir led to a reduced risk of HBV-related events including HCC | |
| Tenofovir | ||||
| HBV | HCC | NCT019553458 | Tenofovir led to a comparable long-term risk of HCC and ICC in CHB patients with entecavir | |
| ISA 101 HPV-16 vaccine | ||||
| HPV | Cervical cancer | ISA 101 + anti-PD-1 antibody nivolumab | NCT02426892 | Concurrent treatment of ISA 101 and anti-PD-1 antibody nivolumab increased both overall response rates and survival of HPV-16-related cancer |
| Cytokine-directed therapies | ||||
| IFN-α | RCC | IFN-α + oblimersen/(iso)tretinoin/isotretinoin/IL-2/chemotherapy (fluorouracil, capecitabine)/sorafenib/VEGF inhibitor (bevacizumab, SU5416)/mTOR inhibitor (CCI-779)/naptumomab estafenatox/pazopanib/celecoxib/thalidomide/chemotherapy (5-Fluorouracil) /pembrolizumab | UMIN000002466, CALGB 90206 | The prolonged IFN-α treatment induced long-lasting complete responses and long-term outcome with acceptable toxicity in patients with metastatic RCC. IFN-α is also a promising combination therapy for target therapies and immune checkpoint inhibitors such as anti-PD-1 therapies |
| Melanoma | IFN-α + combination chemotherapy (dacarbazine, temozolomide, azacitidine, cisplatin)/IL-12/thalidomide/bevacizumab/imatinib/BRAF inhibitor (vemurafenib)/CTLA-4 inhibitor ipilimumab/proteasome inhibitor (PS-341)/sodium stibogluconateRT | NCT00204529, NCT01959633, EORTC 18991, S0008 | Adjuvant treatment with IFN-α-2a or PEG-IFN-α-2b could induce sustained improvement of RFS in stage III melanoma patients and has been approved by the FDA as adjuvant therapy for melanoma | |
| Leukemia | IFNα-2a + combination chemotherapy (melphalan, adriamycin, bleomycin, velban, and dacarbazine)/nilotinib/imatinib/rituximab/dasatinib | NCT02328755, NCT02185261 | IFN-α treatment is an effective strategy for minimal residual disease (MRD)-positive leukemia patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) | |
| Lymphoma | IFN-α + combination chemotherapy (melphalan, adriamycin, bleomycin, velban, and dacarbazine)/bexarotene/rituximab | NCT01609010 | Immunotherapy with IFN-α and rIL-2 is well tolerated and may intensify remission in NHL patients | |
| HCC | IFN-α + chemotherapy (capecitabine)/celecoxib + rintatolimod/thalidomide | IFN-α therapy may reduce HCC recurrence after medical ablation therapy for primary tumors. IFN-α plus cis-platinum is effective in patients with inoperable HCC | ||
| Galunisertib (LY2157299) | ||||
| TGF-β | Pancreatic cancer | Galunisertib + durvalumab/gemcitabine | NCT02734160 | The galunisertib-gemcitabine combination improved OS in patients with unresectable pancreatic cancer with minimal added toxicity |
| HCC | Galunisertib + sorafenib/stereotactic body radiotherapy (SBRT) | NCT01246986 | The combination of galunisertib and sorafenib demonstrated a manageable safety profile and improved prognosis of HCC | |
| Fresolimumab (GC1008) | ||||
| TGF-β | Melanoma, RCC | NCT00356460 | Fresolimumab displayed preliminary antitumor efficacy and acceptable safety profile at multiple doses in patients with advanced melanoma and RCC | |
| PF-03446962 | ||||
| TGF-β | HCC, CRC | Regorafenib + PF-03446962 | NCT00557856 | PF-03446962 had manageable safety and pharmacokinetic profiles in HCC, but the combination of regorafenib and PF-03446962 caused unacceptable toxicity with limited clinical activity in patients with refractory metastatic CRC |
| Bintrafusp alfa (M7824) | ||||
| TGF-β and PD-L1 | NSCLC | Bintrafusp alfa + chemotherapy (docetaxel, platinum-based) | NCT02517398 | Bintrafusp alfa induced promising efficacy and manageable tolerability in patients with NSCLC previously treated with platinum |
| HPV-associated cancer | NCT02517398, NCT02517398, NCT04247282 | Bintrafusp alfa showed clinical activity and manageable safety in HPV-associated cancers | ||
| Esophageal cancer | NCT02517398, NCT02699515 | Bintrafusp alfa showed clinical activity with manageable safety profile in patients with advanced esophageal adenocarcinoma | ||
| Anakinra | ||||
| IL-1 | Multiple myeloma | Anakinra + immunomodulatory drug combination lenalidomide and dexamethasone | NCT00635154 | Anakinra decreased the proliferative rates of tumor, leading to a chronic disease state with improved PFS in patients with multiple myeloma at high risk of progression to active myeloma |
| CRC | Anakinra + 5-FU + bevacizumab | 5-FU plus bevacizumab and anakinra had promising activity and a manageable safety profile in refractory metastatic CRC | ||
| Bempegaldesleukin (NKTR-214) | ||||
| IL-2 | Melanoma | Bempegaldesleukin + nivolumab/pembrolizumab | NCT03635983, PIVOT-02 | Bempegaldesleukin can be used in combination with nivolumab or pembrolizumab in patients with metastatic melanomas |
| Urothelial carcinoma | Bempegaldesleukin + nivolumab | NCT02983045, PIVOT-02 | Bempegaldesleukin combined with nivolumab is suggested as the first-line therapy for patients with metastatic urothelial carcinoma with manageable side effects | |
| Nemvaleukin alfa (LKS 4230) | ||||
| IL-2 | Ovarian cancer | Nemvaleukin alfa + pembrolizumab | NCT05092360 | Under evaluation for the efficacy and safety as monotherapy and combination therapy with pembrolizumab in patients with platinum-resistant ovarian cancer |
| CNTO 328 | ||||
| IL-6 | Multiple myeloma | Siltuximab + bortezomib-melphalan-prednisone (VMP) | NCT00911859 | The addition of siltuximab to the bortezomib-melphalan-prednisone (VMP) regimen did not improve the complete response rate or long-term outcomes of MM patients |
| Prostate cancer | Siltuximab + mitoxantrone/prednisone | SWOG S0354 | Siltuximab was well tolerated and improved clinical outcomes, leading to a PSA response rate of 3.8% and a stable disease rate of 23% in patients with castration-resistant prostate cancer | |
| Tocilizumab | ||||
| IL-6R | Ovarian cancer | Tocilizumab + carboplatin/doxorubicin | NCT01637532 | Tocilizumab at 8 mg/kg combined with carboplatin/doxorubicin chemotherapy is feasible and safe for the treatment of ovarian cancer |
| Pegilodecakin (LY3500518) | ||||
| IL-10 | Solid tumors | Pegilodecakin + chemotherapies or anti-PD-1 blockade | NCT02009449 | Pegilodecakin was used as monotherapy and in combination with chemotherapies or anti-PD-1 blockade to treat tumors such as melanoma, NSCLC, CRC, and pancreatic cancer |
| Chemokine-directed therapies | ||||
| Carlumab | ||||
| CCL2 | Prostate cancer | Carlumab could be safely administered in patients with metastatic CRPC, but failed to demonstrate significant antitumor activities as a single agent | ||
| PF-04136309 | ||||
| CCR2 | ||||
| Pancreatic cancer | PF-04136309 + chemotherapy (gemcitabine plus nab‐paclitaxel) | NCT02732938 | PF-04136309 in combination with nab-paclitaxel plus gemcitabine may induce pulmonary toxicity, with no significant superior efficacy signal over nab-paclitaxel and gemcitabine | |
CML, chronic myeloid leukemia; AML, acute myeloid leukemia; HCC, hepatocellular carcinoma; NSCLC, non-small cell lung cancer; ICC, intrahepatic cholangiocarcinoma; SCCHN, squamous cell carcinoma of head and neck; ALL, acute lymphocytic leukemia; CNS, central nervous system; SCLC, small cell lung cancer; PDAC, pancreatic ductal adenocarcinoma; RT, radiation therapy; EGFR, epidermal growth factor receptor; TKIs, tyrosine kinase inhibitors; PSA, prostate-specific antigen