Table 4.
Summary of current clinical trails involving combination strategies with HDACI.
| HDACI | Combination | Phase | Disease | Patient number | Response |
|---|---|---|---|---|---|
| Vorinostat | Carboplatin/Paclitaxel | I | Advanced solid tumors | 25/28 patients available for evaluation | NSCLC patients were best responders; PR (53%), SD (21%) |
| FOLFOX | I | Refractory colorectal cancer | 21 patients enrolled | Study resulting in a determined vorinostat MTD of 300 mg 2× daily in combination with FOLFOX | |
| Doxorubicin | I | Solid tumors | 24/32 patients available for evaluation | PR (8%; prostate and breast cancer patients); SD (8%; melanoma patients) | |
| Docetaxel | I | CRPC and NSCLC | NA | Study terminated due to excessive DLTs | |
| Gemcitibine/cisplatinum | I | Metastatic NSCLC | 19/28 patients available for evaluation | PR (47%) | |
| Erlotinib | I | Refractory NSCLC | 9 patients available for evaluation | SD (67%) | |
| Bortezomib | I | Refractory solid tumors | 29 patients available for evaluation | Study resulted in a determined vorinostat MTD of 300 mg BID with bortzomid dosed at 1.3 mg/m2. Evidence of clinical activity was observed | |
| Bevacizumab | II | Stage IV clear cell renal carcinoma | 32/34 patients available for evaluation | 18% objective responses (1× CR; 5× PR), 67% (SD). Median progression free survival: 5.3 months Overall survival: 16.2 months | |
| Sorafenib | I | Advanced solid tumors | 12/17 patients available for evaluation | 1 unconfirmed PR; 9 SD (minor responses). MTD/RP2D in combination recommended is 300 mg vorinostat QD d 1–14 with 400 mg sorafenib BID d 1–21 (21 day cycles). | |
| Flavopiridol | I | Advanced solid tumors | 31/34 patients evaluable for evaluation | Concluded that intermittent pulsing of high dose vorinostat in combination with flavopiridol is achievable without increased toxcities. RP2D is 800 mg vorinostat (3 days; d 1–3) with 30 mg/m2 flavopiridol (30min followed by 30 mg/m2 every over 4h every 14d). | |
| Romidepsin | Gemcitibine | I | Advanced solid tumors | 33 patients available for evaluation | SD (36%) |
| Bortezamib | II | Refractory/relapsed multiple myeloma | 5 patients currently enrolled | Concluded that this combination is active and further patient recruitment is currently underway | |
| Entinostat | Erlotinib | I | Advanced NSCLC | 9 patients available for evaluation | PR (11%) and SD (11%) |
| 5-azacitidine | II | Relapsed advanced NSCLC | 25 patients currently enrolled | CR (4%) and SD (8%); remaining patients had PD | |
| Aromatase inhibitor therapy | II | ER+ breast cancer | 27 patients enrolled | 1 confirmed PR; 1 SD > 6 months. Concluded this combination demonstrated clinical benefit. | |
| Panobinostat | Trastuzumab | I | HER2 positive metastatic breast cancer | 18 patients enrolled | Preliminary data indicates this combination to be well tolerated and displays clinical activity |
| Lenalidomide/ dexamethasome | I | Relapsed/refractory multiple myeloma | 22 patients enrolled | Combination well tolerated with indications of clinical efficacy | |
| Docetaxel | Ib | Chemotherapy naïve CRPC | 21 patients enrolled | Minimal DLTs have been observed with some patients achieving a biochemical response indicated by reduced PSA levels | |
| Epirubicin | I | Solid tumors | 10 patients | Patient cohort treated with 50 mg panobinostat reported to date and concluded that sequence combination of panobinostat and epirubicin is well tolerated. |