Background: Laryngeal bio-selection with induction chemotherapy (platinum + 5-FU infusion: PF) has been demonstrated to result in impressive rates of survival and organ preservation with moderate toxicities. We sought to reduce the toxicity of PF by substituting docetaxel (T) for 5-FU and improve the tumor response rate with the addition of the Bcl-xL inhibitor AT-101. Methods: Pts with advanced stage laryngeal cancer were treated with 1 cycle of T 75 mg/m2 + platinum (P) (cisplatin 100 mg/m2 or carboplatin AUC 6) and were randomized 2:1 to the addition of AT-101. Patients with a CR proceeded to chemoradiation (CRT) with concurrent weekly P. All pts with PR or NR underwent a second cycle of induction with TP + AT-101. Pts with a > 50% response (CR or PR) after the second cycle of induction chemotherapy underwent CRT. Pts with a ≤ 50% response (NR) underwent laryngectomy. PET-CT was performed 12 weeks after CRT. Pts with residual disease underwent salvage laryngectomy (SL). Results: 54 eligible pts were enrolled; 46 M, 8 F; median age 59; 26 T4; stage III 16, stage IV 38; site: 2 hypopharyngeal, 39 supraglottic, 11 glottic, 2 subglottic. After cycle 1 of induction, 2/54 (4%) died prior to assessment by DL and 2 were removed from protocol due to adverse events (AEs). 29/50 pts (58%) had ≥ 50% response, 3 of which had CR; 2 proceeded to CRT & 1 received a 2^nd cycle of IC. 21/50 pts (42%) had < 50% response. A total of 48 pts received cycle 2 of IC. After the 2^nd cycle, a total of 39/50 pts (78%) had ≥ 50% response & received CRT. No difference in response was seen with addition of AT-101. 11/50 pts (22%) had < 50% response- 8 had laryngectomy & 3 refused. Following CRT, 10 pts underwent SL, 2 for residual disease & 8 late SL. The organ preservation rate was 31/50 (62%). The most common grade 3/4 toxicities associated with IC were nausea 9%, neutropenia 9%, & infection 7%. 1 pt died of CNS hemorrhage unrelated to therapy & 1 from sepsis. The median follow-up time is 28 months. The 2 yr laryngectomy-free survival is 54% (95% CI:38-68) & 2 yr overall survival is 81% (95% CI: 64-90). Conclusions: AT-101 did not improve responses to P. Treatment with 2 cycles of IC with PT produced similar response rates to our institutional controls, but organ preservation was somewhat less following treatment with weekly P + RT. Toxicities were overall improved with this treatment strategy. Clinical trial information: NCT01633541