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Table 1 Phase I Results of Vorinostat in Combination Therapy in Patients with Advanced Solid Tumors

From: Vorinostat in solid and hematologic malignancies

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]
  1. DLT, dose-limiting toxicity; ALT, alanine aminotransferase; MTD, maximum tolerated dose; PR, partial response; DVT, deep vein thrombosis; CR, complete response; PR, partial response; SD, stable disease; PD, disease progression; NE, not evaluable; NSCLC, non-small-cell lung cancer; AUC, area under the curve; 5-FU/LV, 5-fluorouracil/leucovorin.