Drugs and Clinical Approaches Targeting the Antiapoptotic Protein: A Review

Table 1

2010–2019 Clinical trials of Bcl-2 inhibitors.

Bcl-2 inhibitor	Combined therapy with other drugs	Targeted cancer type	No. of patients	Complete remission	Partial response	Stable disease	Phase	Researchers
Oblimersen	Cisplatin and 5-fluorouracil	Advanced esophageal, gastroesophageal junction, and gastric carcinoma	15	1 (metastatic gastric carcinoma with pulmonary metastases)	2 (1 gastric carcinoma, 1 squamous cell carcinoma of the esophagus)		I	Raab et al. [7]
	Gemcitabine	Refractory and advanced malignancies	16	0	0	5	I	Galatin et al. [8]
	Temozolomide and albumin-bound paclitaxel	Advanced melanoma	32	2	11	11	I	Ott et al. [9]
Navitoclax (ABT-263)	None	SCLC or pulmonary carcinoid	47	0	1 (SCLC)	8 (5 SCLC, 3 atypical pulmonary carcinoid)	I	Gandhi et al. [10]
	None	Relapsed SCLC	39	0	1	9	II	Rudin et al. [11]
	None	Relapsed or refractory CLL	29	0	9	7	I	Roberts et al. [12]
	Irinotecan	Advanced solid tumors	31	0	2 (1 Merkel cell carcinoma, 1 colon carcinoma)	6	I	Tolcher et al. [13]
	Erlotinib	Advanced solid tumors	11	0	0	3	I	Tolcher et al. [14]
	Rituximab	Relapsed or refractory CD20^+ lymphoid malignancies	29	6 (1 diffuse large B-cell lymphoma, 5 follicular lymphoma)	10 (5 CLL/SLL, 4 follicular lymphoma, 1 lymphoma/Waldenström’s macroglobulinemia)		I	Roberts et al. [15]
	Rituximab	Previously untreated B-cell CLL	78	2	47	25	II	Kipps et al. [16]
Venetoclax (ABT-199)	Obinutuzumab	CLL and coexisting conditions	216	107	76		III	Fischer et al. [17]
	Ibrutinib	CLL	80	25	1		II	Jain et al. [18]
	Ibrutinib	CLL	91	8	48	22	II	Jones et al. [19]
	None	Relapsed or refractory non-Hodgkin lymphoma	106	14	33	32	I	Davids et al. [20]
	None	Acute myelogenous leukemia	32	6 (2 CR, 4 CRi)	0	6	II	Konopleva et al. [21]
	Decitabine or azacitidine	Acute myeloid leukemia	57	35	1	0	I	DiNardo et al. [22]
	Bendamustine and obinutuzumab	CLL	66	5	55		II	Cramer et al. [23]
Obatoclax mesylate (GX15-070)	Bortezomib	Relapsed or refractory mantle cell lymphoma	13	3	1	6	I/II	Goy et al. [24]
	None	Myelodysplastic syndromes with anemia or thrombocytopenia	24	0	0	17	II	Arellano et al. [25]
AT-101	Paclitaxel and carboplatin	Several types of solid tumors (most common tumor type was prostate, N = 11)	24	1 (esophageal cancer)	4 (1 NSCLC, 3 prostate)		I	Stein et al. [26]
	Docetaxel	Recurrent, locally advanced, or metastatic head and neck cancer	22	0	3	12	II	Swiecicki et al. [27]
	Cisplatin and etoposide	Extensive-stage SCLC	27	0	10	11	I	Schelman et al. [28]

CLL, chronic lymphocytic leukemia; CRi, complete response with incomplete blood count recovery; NSCLC, non-small-cell lung cancer; SCLC, small-cell lung cancer; and SLL, small lymphocytic leukemia.