Table 1. Published phase II/III clinical trials of drugs targeting the Bcl-2 family.
| Study description | Tumor entity | Study summary | Reference |
|---|---|---|---|
| Phase II trial of oblimersen as a single treatment | advanced CLL | 2/26 patients achieved PR; 7/17 patients showed ≥50% reduction in splenomegaly; 2/7 patients showed complete disappearance of hepatomegaly; 7/22 patients showed ≥ 50% reduction of lymphadenopathy; 11/22 patients showed ≥50% reduction in circulating lymphocyte count | O'Brien et al.99 |
| Phase III trial of fludarabine plus cyclophosphamide with (group 1) or without (group 2) oblimersen | Relapsed or refractory CLL | 17 % CR in group 1 versus 7% CR in group 2. Among patients with CR, response duration was significantly longer in group 1 versus group 2 (>36 months versus 22 months); 40% of patients with CR or PR of group 1 showed a significant 5-year survival benefit | O'Brien et al.128 |
| Phase II trial of oblimersen in combination with rituximab | Recurrent B-cell non-Hodgkin lymphoma | CR in 23 % patients, a PR in 19 % patients and 28 % patients showed a minimal response or stable disease | Pro et al.101 |
| Phase II trial of oblimersen in combination with gemtuzumab ozogamicin | AML | 12/48 patients (25%) achieved a major response with 5 CR and 7 CR without platelet recovery. Ten of the 12 patients who achieved a major response survived >6 months compared with six of 36 nonresponders | Moore et al.102 |
| Phase II trial of oblimersen in combination with dexamethasone and thalidomide | Relapsed MM | 55% of patients achieved objective responses, including CR in 2/33 patients, 4/33 near CRs, PR in 12/33 patients and 6/33 patients had minimal responses | Badros et al.103 |
| Phase III trial of dexamethasone with (group 1) or without oblimersen (group 2) | Advanced MM | No significant differences between the two groups in time to tumor progression or objective-response rates | Chanan-Khan et al.105 |
| Phase II trial oblimersen in combination with dacarbazine | Advanced melanoma | The addition of oblimersen to dacarbazine yielded a trend toward improved survival at 24-month minimum follow-up (median, 9.0 versus 7.8 months; P=077) and significant increases in progression-free survival (median, 2.6 versus 1.6 months; P<001), overall response (13.5 versus 7.5% P=007), complete response (2.8 versus 0.8%), and durable response (7.3 versus 3.6% P=03) | Bedikian et al.104 |
| Phase II trial of docetaxel in combination with oblimersen | Castration-resistant prostate cancer | No statistical difference in overall survival | Sternberg et al.106 |
| Phase I/II trial of gossypol in combination with topotecan | Relapsed and refractory SCLC | No convincing clinical activity | Heist et al.115 |
| Phase II trial of gossypol in combination with docetaxel | NSCLC | No convincing clinical activity | Ready et al.117 |
| Phase II trial of gossypol | Chemotherapy-sensitive recurrent extensive-stage SCLC | No observed clinical activity | Baggstrom et al.118 |
| Phase II trial of docetaxel plus prednisone in combination with gossypol | Metastatic castration-resistant prostate cancer | No statistical difference in overall survival | Sonpavde et al.119 |
| Phase II trial of obatoclax mesylate | Myelofibrosis | No convincing clinical activity | Parikh et al.132 |
| Phase II trial of Abt-263 | Relapsed SCLC | PR in 2.6% and stable disease in 23% patients. The most common toxicity associated with navitoclax was thrombocytopenia, which reached grade III–IV in 41% of patients. |
Abbreviations: AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia; CR, complete remission; MM, multiple myeloma; NSCLC, non-small cell lung cancer; PR, partial remission; SCLC, small cell lung cancer