Table 3.
List of CDK inhibitors described in clinical study section.
| Treatment | Clinical Trial Phase | Disease(s) | Response Rate | Adverse Effects | Refs. |
|---|---|---|---|---|---|
| Flavopiridol | Phase I | relapsed myeloma | 1/50 (2%) | diarrhea, cytopenias, transaminase elevation | [59] |
| Flavopiridol in combination with doxorubicin | Phase I | advanced sarcomas | 19/28 (68%) | neutropenia, leukopenia, febrile neutropenia | [60] |
| Flavopiridol in combination with imatinib mesylate | Phase I | Bcr-Abl + chronic myelogenous leukemia | 5/21 (24%) | anemia, leukopenia, lymphopenia, thrombocytopenia | [61] |
| Flavopiridol in combination with cisplatin | Phase II | platin-resistant ovarian and primary peritoneal carcinoma | 17/40 (43%) platin-resistant patients; 4/5 (80%) platin-sensitive patients | neutropenia, nausea, vomiting, fatigue, thrombosis, anemia | [62] |
| Flavopiridol in combination with cyclophosphamide and rituximab | Phase I | chronic lymphocytic leukemia | 7/9 (78%) | fatigue, electrolyte disturbances, diarrhea, abdominal discomfort, nausea/vomiting, liver dysfunction, anemia, leukopenia, neutropenia, thrombocytopenia | [63] |
| Flavopiridol | Phase I/II | chronic lymphocytic leukemia | 112/52 (46%) | n.a. | [64] |
| Flavopiridol | ? | chronic lymphocytic leukemia | 41/95 (43%) ≥70 years old; 10/21 (47%) <70 years old | tumor lysis syndrome, cytokine release syndrome, neutropenia, diarrhea, fatigue | [65] |
| Flavopiridol in combination with bortezomib | Phase I | refractory B-cell neoplasms | 7/16 (44%) | neutropenia, lymphopenia, and thrombocytopenia | [66] |
| Flavopiridol in combination with bortezomib | Phase I | Refractory indolent B-cell neoplasms | 13/39 (33%) | leukopenia, lymphopenia, neutropenia, thrombocytopenia, diarrhea, fatigue, sensory neuropathy | [67] |
| Dinaciclib in combination with aprepitant | Phase I | advanced malignancies | n.a. | no change in safety profile of dinaciclib | [44] |
| Dinaciclib | Phase I | advanced malignancies | 10/48 (21%) | nausea, anemia, decreased appetite and fatigue | [68] |
| Dinaciclib | Phase I | relapsed and/or refractory acute myeloid leukemia | 12/20 (60%) | diarrhea, fatigue, transaminitis, manifestations of tumor lysis syndrome; one patient deceased of acute renal failure | [69] |
| Dinaciclib vs. erlotinib | Phase II | non-small cell lung cancer | Not successful | neutropenia, leukopenia, vomiting, diarrhea | [70] |
| Dinaciclib vs. capecitabine | Phase II | advanced breast cancer | 2/7 (29%) (not superior to capecitabine) | neutropenia, leukopenia, increase in aspartate aminotransferase, febrile neutropenia | [71] |
| Dinaciclib vs. capecitabine | Phase I | chronic lymphocytic leukemia | 5/6 (83%) | hematological, digestive and metabolic; no dose-limiting toxicities | [72] |
| Dinaciclib | Phase I/II | relapsed multiple myeloma | 3/27 (11%) | leukopenia, thrombocytopenia, gastrointestinal symptoms, alopecia, fatigue | [74] |
| PD 0332991 | Phase I | advanced cancer | 10/37 (27%) | neutropenia, anemia, leukopenia, fatigue, nausea, diarrhea | [75] |
| PD 0332991 | Phase I | advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma | 19/29 (66%) | anemia, thrombocytopenia, neutropenia, febrile neutropenia | [76] |
| PD 0332991 | Phase II | advanced breast cancer | 20/37 (%) | neutropenia, leucopenia, lymphopenia, thrombocytopenia | [77] |
| PD 0332991 in combination with letrozole vs. letrozole alone | Phase II | advanced breast cancer | 87% vs. 57% (66 patients) | neutropenia, leukopenia, and fatigue | [78] |
| LY2835219 | Phase I | metastatic breast cancer | 33/47 (70%) | diarrhea, nausea, fatigue, neutropenia, vomiting, decreased platelet and white-blood cell counts | [46] |
| PHA-793887 | Phase I | solid tumors | n.a. | severe, dose-related hepatic toxicity | [48] |