A randomized,double-masked,crossover comparison of the efficacy and safety of botulinum toxin type A produced from the original bulk toxin source and current bulk toxin source for the treatment of cervical dystonia

In 1997, the US FDA approved a new bulk toxin source (now referred to as current) for the manufacture of botulinum toxin type A (BTX-A). The current BTX-A preparation has a lower neurotoxin complex protein load than the original BTX-A preparation, which may reduce antigenic potential. The present double-masked, multicenter study compared the efficacy and safety of BTX-A (BOTOX) produced from both original and current bulk toxin sources for the treatment of cervical dystonia. Patients (N = 133) were injected with BTX-A produced from original and current bulk toxin sources using a crossover design. Adverse events were assessed at each visit. Efficacy was assessed at 2 and 6 weeks post-injection using the severity and pain-disability subscales of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Mean BTX-A doses were comparable (original: 155 U, current: 156 U). Both BTX-A preparations produced similar, statistically significant reductions in TWSTRS severity and pain-disability scores at weeks 2 and 6 post-injection. The original and current BTX-A preparations showed no significant differences in adverse events, including both treatment-related (34%, 31%) and treatment-unrelated (27%, 32%), respectively. BTX-A produced from the original and current bulk toxin sources showed comparable efficacy and safety in the treatment of cervical dystonia; both significantly reduced dystonia severity and pain.     

Phase III multicenter clinical trial of the sialyl-TN (STn)-keyhole limpet hemocyanin (KLH) vaccine for metastatic breast cancer

Purpose.

This double-blind, randomized, phase III clinical trial evaluated time to progression (TTP) and overall survival in women with metastatic breast cancer (MBC) who received sialyl-TN (STn) keyhole limpet hemocyanin (KLH) vaccine. Secondary endpoints included vaccine safety and immune response.

Experimental design.

The study population consisted of 1,028 women with MBC across 126 centers who had previously received chemotherapy and had had either a complete or a partial response or no disease progression. All women received one-time i.v. cyclophosphamide (300 mg/m²) 3 days before s.c. injection of 100 μg STn-KLH plus adjuvant (treatment group) or 100 μg KLH plus adjuvant (control group) at weeks 0, 2, 5, and 9. Subsequently, STn-KLH without adjuvant or KLH without adjuvant was then administered monthly for 4 months, and then quarterly until disease progression, without cyclophosphamide.

Results.

STn-KLH vaccine was well tolerated; patients had mild to moderate injection-site reactions and reversible flu-like symptoms. Week-12 antibody testing revealed high specific IgG titers and a high rate of IgM-to-IgG seroconversion; the median IgG titers in STn-KLH recipients were 320 (anti-ovine submaxillary mucin) and 20,480 (anti-STn), with no detectable antimucin antibodies in the control group. The TTP was 3.4 months in the treatment group and 3.0 months in the control group. The median survival times were 23.1 months and 22.3 months, respectively.

Conclusions.

Although STn-KLH was well tolerated in this largest to date metastatic breast cancer vaccine trial, no overall benefit in TTP or survival was observed. Lessons were learned for future vaccine study designs.     

Postoperative Performance of the Quartet® Left Ventricular Heart Lead

Promote^® Q CRT‐D and Quartet^® LV Lead Study . Introduction: The Quartet^® left ventricular (LV) lead is the first with 4 pacing electrodes (tip and 3 rings) that enables pacing from 10 different pacing vectors. Postoperative performance of this lead was evaluated in a prospective, nonrandomized, multicenter IDE study. Methods: Patients with standard indications for CRT‐D were enrolled. Electrical performance and presence of phrenic nerve stimulation (PNS) were assessed during pacing from each of 10 vectors at predischarge (within 7 days), 1 month, and 3 months postimplant. Results: The Quartet LV lead was implanted successfully in 170 patients (95.5% implant success rate, 68 ± 11 years, 68.5% male, LVEF: 25 ± 7%, NYHA class III: 98.3% and class IV: 1.7%). Mean follow‐up was 4.7 ± 1.9 months. Capture threshold and impedance for each of the 10 LV lead pacing vectors remained stable during follow‐up. LV lead dislodgement occurred in 6 (3.5%) patients and PNS was observed in 23 (13.5%) patients. PNS was resolved noninvasively in all 23 (100%) patients, either by reprogramming to pace from the additional LV lead pacing vectors alone (13 pts, 56.5%), reprogramming to pace from the additional LV lead pacing vectors and reprogramming pacing output (4 pts, 17.4%), or by reprogramming pacing output alone (6 pts, 26.1%). Conclusions: The Quartet LV lead electrical performance was stable and was associated with a high implant success and low dislodgement rate during 3‐month follow‐up. In all patients with PNS, the 10 pacing vectors combined with reduced output programming enabled the elimination of PNS noninvasively. (J Cardiovasc Electrophysiol, Vol. 24, pp. 449‐456, April 2013)