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Table 2 Phase I Results of Vorinostat in Combination Therapy in Patients With Hematologic Malignanciesa

From: Vorinostat in solid and hematologic malignancies

Tumor Type No. Pts Treatment Summary of Results Ref
Relapsed multiple myeloma 23 Vorinostat + bortezomib DLTs: prolonged QT interval (1), fatigue (1)
MTD vorinostat 400 mg qd on Days 4–11 + bortezomib 1.3 mg/m2 on Days 1, 4, 8, and 11 every 21 days
Response: 2 VGPR, 7 PR, 10 SD (21 evaluable patients)
[78]
Relapsed, refractory or poor prognosis acute leukemia or refractory anemia with excess blasts-2 22 Vorinostat + flavopiridol (bolus or 'hybrid' infusion schedules) DLTs: infectious colitis with sepsis (1 [bolus]) and atrial fibrillation (1 ['hybrid'])
MTD: not yet reached on vorinostat 200 mg tid given in a 'hybrid' schedule with flavopiridol at 30/30 mg/m2 (load/infusion) on Days 1 and 8 of a 21-day cycle, identification of the MTD and recommended phase II dose is ongoing
Response: 10 patients experienced some clinical benefit (20 evaluable patients)
[81]
Advanced acute leukemia 20 Vorinostat + idarubicin DLTs: myelosuppression, encephalopathy, and dysphagia
2 CR and 2 complete marrow responses observed in patients who had failed previous anthracycline-based therapy
Recruitment ongoing at vorinostat 400 mg tid for 3 days + idarubicin 12 mg/m2 for 3 days every 14 days
[82]
Relapsed or newly-diagnosed acute myelogenous leukemia or myelodysplastic syndrome 70 Vorinostat + decitabine (concurrent or sequential regimens) DLT: prolonged QT interval (1 [sequential])
Response: concurrent (n = 34), 7 CR, 2 PR, 2 HI, 12 SD; sequential (n = 36), 3 CR, 2 HI, 16 SD
MTD not reached
Last cohort: vorinostat 400 mg qd for 14 days (Days 1–14 concurrent or Days 6–19 sequential) + decitabine 20 mg/m2/day on Days 1–5 every 28 days
[83]
Relapsed, refractory or poor prognosis leukemia 31 Vorinostat + decitabine DLTs: pulmonary embolism and diarrhea (1)
Response: 1 CR, 4 significant reduction in bone marrow blasts, 4 SD, 14 PD, 7 NE (30 evaluable patients)
Last cohort: decitabine 25 mg/m2 daily for 5 days followed by vorinostat 200 mg tid for 14 days
[84]
Relapsed or refractory multiple myeloma 18 Vorinostat + lenalidomide + dexamethasone DLTs: none yet reported
MTD: not yet reached, DLT evaluation ongoing in patients enrolled to vorinostat 400 mg qd for 14 days (Days 1–7 and 15–21), combined with lenalidomide 25 mg qd for 21 days, and dexamethasone 40 mg/day (Days 1, 8, 15, and 22) every 28 days
Response: 1 CR, 4 PR, 1 MR, 5 SD (15 evaluable patients)
[87]
Myelodysplastic syndrome and acute myeloid leukemia 28 Vorinostat + azacitidine DLTs: not reported
Response: 9 CR, 2 incomplete CR, 7 HI, 2 SD (21 evaluable patients)
Last cohort: azacitidine 55 mg/m2/day on Days 1–7 + vorinostat 300 mg bid on Days 3–5 every 28 days
[85]
Advanced multiple myeloma 34 Vorinostat + bortezomib DLTs: transient AST elevation (1), thrombocytopenia (1)
MTD not yet reached, the maximum administered dose was vorinostat 400 mg qd on Days 1–14 + bortezomib 1.3 mg/m2 on Days 1, 4, 8, and 11 every 21 days.
Response: 12 PR, 6 MR, 13 SD (33 evaluable patients). In 17 evaluable patients who had received prior bortezomib therapy, 6 PR, 4 MR, 7 SD
[79]
Acute myeloid leukemia 27 Vorinostat + decitabine DLT: fatigue (1)
Response: 1 incomplete CR, 1 morphologic leukemia-free (without neutrophil recovery), 3 PR (25 evaluable patients)
MTD not reached: maximum dose vorinostat 200 mg bid on Days 1–21 + decitabine 20 mg/m2/day on Days 1–5 every 28 days
[86]
  1. aOnly trials including at least 15 patients are reported in this table.
  2. DLT, dose-limiting toxicity; AST, aspartate aminotransferase; MTD, maximum tolerated dose; PR, partial response; MR, minimal response; SD, stable disease; VGPR, very good partial response; nCR, near complete response; PD, progressive disease; CR, complete response; NE, not evaluable; HI, hematologic improvement.