Table 2 Clinical trials of decitabine-based therapies for solid tumors
Drugs used in combination with decitabine | Regimen | Tumor types | Phase | Patient number | Results | Major toxicity | Response pulse stable disease rate (%) | Year |
|---|---|---|---|---|---|---|---|---|
Cisplatin | DAC in four (I–IV) dose escalation levels (45, 67, 90 to 120 mg/m/day 1–3) infusion followed by cisplatin 33 g/m2/day 1 infusion (21-day circle) | Non small cell lung cancer (NSCLC) | I/II | 14 | PD:14/14 | Neutropenia and thrombocytopenia | 0 | 2000 |
Cisplatin | DAC 50Â mg/m2/day followed by cisplatin 30Â g/m/day 3-h infusion (21-day cycle) | Advanced cervical cancer(most of them are squamous cell carcinoma of the cervix) | II | 25 | PR:8/21 SD:5/21 PD:8/21 | Hematologic toxicity | 62 | 2002 |
Carboplat | DAC 90Â mg/m2 on day1 6-h infusion followed by carboplat in on day8 (28-days circle) | Solid tumors (colon, breast, ovary, melanoma, sarcoma, gall bladder and pleural mesothelioma) | I | 35 | PR:1/10 SD:3/10 PD:6/10 | Myelosuppression | 40 | 2007 |
Carboplat | DAC (10 or 20Â mg/m2/day1-8 and carboplatin on day 8 (28-day cycle) | Platinum-resistant ovarian cancer | I | 10 | CR:1/10 SD:6/10 PD:3/10 | Nausea, allergic reactions and neutropenia | 70 | 2010 |
Carboplat | DAC 10Â mg/m2 for day1-5 and carboplatin on day 8 (28-day cycle) | Platinum-resistant ovarian cancer | II | 17 | CR:1/17 PR:5/17 SD:6/17 PD:5/17 | Nausea | 70 | 2012 |
Carboplat | DAC 90 mg/m2 day1 infusion followed by carboplat infusion on day 8 (28-days circle) | Relapsed ovarian cancer | II | 15 | PR + SD:1/12 PD:11/12 | Neutropenia | 8 | 2014 |
Carboplat | DAC 7 mg/m2 day 1–5 followed by reduced TC treatment (28-day circle) | Relapsed or refractory ovarian cancer | I/II | 21 | PR:3/17 SD:9/17 PD:5/17 | Nausea and neutropenia | 71 | 2015 |
Carboplat | DAC 7 mg/m2 day 1–5 followed by reduced TC treatment on day 6 (28-days circle) | Recurrent ovarian cancer | I/II | 40 | CR:1/40 PR:8/40 SD:19/40 PD:12/40 | Nausea | 74 | 2017 |
Doxorubicin and cyclophosphamide | DAC (5–10 mg/m2/day 1–7 1-h infusion followed by doxorubicin (45 mg/m) and cyclophosphamide (1 g/m) on day 7 | Children refractory solid tumors (neuroblastomar,habdomyosarcoma, osteosarcoma) | I | 21 | SD:7/21 PD:14/21 | Neutropenia and thrombocytopenia | 33 | 2010 |
Vorinostat | DAC 10 mg/m2/day1-5 and vorinostat 200 mg twice a day on days6-12 (28-days circle) | Advanced solid tumors and non-Hodgkin’s lymphomas | I/II | 43 | SD:11/38 PD:27/38 | Neutropenia and thrombocytopenia | 29 | 2011 |
anti-EGFR | DAC 45Â mg/m2/day 1 and 15 and followed by anti-EGFR 6Â mg/kg /day 8 and 22 (28-day cycle) | wt KRAS metastatic colorectal cancer | I/II | 20 | PR:2/20 SD:10/20 PD:8/20 | Rash and hypomagnesemia | 60 | 2013 |
Vemurafenib | 3 + 3 dose escalation combining subcutaneous decitabine at different doses and schedules (4 cohorts) with the standard oral dose of vemurafenib 960 mg twice daily | Metastatic melanoma | I/II | 14 | CR:3/14 PR:3/14 SD:5/14 OD:3/14 | Fatigue and increased creatinine | 79 | 2017 |