Table 1 Phase I Results of Vorinostat in Combination Therapy in Patients with Advanced Solid Tumors
Tumor Type | No. Pts | Treatment | Summary of Results | Ref |
|---|---|---|---|---|
Advanced solid | 22 | Vorinostat + pemetrexed + cisplatin | DLTs: fatigue (2), dehydration (2), neutropenia (1), cerebral ischemia (1) DVT (1) 19 patients evaluable for response: 1 CR, 1 PR, 11 SD, 6 PD Vorinostat 300 mg qd for 7/21 days was tolerable with cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 | [70] |
Advanced solid | 20 | Vorinostat + doxorubicin | DLTs: thrombocytopenia (1), fatigue (1), nausea/vomiting, and anorexia (1) Response: 1 PR, 3 SD, 11 PD, 5 NE Tolerated dose of vorinostat higher than approved single-agent dose in patients with hematologic malignancies | [71] |
Advanced colorectal | 21 | Vorinostat + 5-FU/LV + oxaliplatin | DLTs: fatigue (1), fatigue and diarrhea (1), fatigue, anorexia, and dehydration (1) Response: 11 SD (5 confirmed) of 21 evaluable patients Recommended dose: vorinostat 300 mg bid on Days 1–7 + 5-FU/LV + oxaliplatin on Day 4 every 14 days | [74] |
Advanced solid | 28 | Vorinostat + carboplatin + paclitaxel | DLTs: vomiting (1), febrile neutropenia (1) Response: 11 PR, 7 SD in 25 evaluable patients (of 19 pts with NSCLC [18 chemonaïve], 10 [53%] had a PR) Phase II regimen: vorinostat 400 mg qd on Days 1–14 + carboplatin AUC 6 mg/mL × min + paclitaxel 200 mg/m2 | [68] |
Refractory solid | 22 | Vorinostat + bortezomib | DLTs: fatigue (3), hyponatremia (1), elevated ALT (1) MTD (step A): vorinostat 400 mg qd on Days 1–14 + bortezomib 1.3 mg/m2 on Days 1, 4, 8, and 11 of a 21-day cycle Clinical activity observed: 1 PR >9 months in a patient with refractory soft tissue sarcoma | [72] |
Advanced solid | 26 | Vorinostat + capecitabine | DLTs: diarrhea (1), fatigue (2), nausea/vomiting (1) Response: 4 PR (3 confirmed), 18 SD, 4 PD Recommended Phase II regimen: vorinostat 300 mg qd + capecitabine 1000 mg/m2 bid | [73] |
Malignant glioma | 19 | Vorinostat + temozolomide | DLTs: thrombocytopenia (2), fatigue (3), nausea (1) MTD: vorinostat 300 mg qd on Days 1–14 + temozolomide 150 mg/m2/day on Days 1–5 every 28 days | [69] |