Purpose: To assess safety, pharmacokinetics, maximum tolerated dose, and preliminary efficacy of bivatuzumab mertansine. Bivatuzumab is a humanized monoclonal antibody directed against CD44v6, which previously seemed to be safe in phase I radioimmunotherapy trials, whereas the conjugated mertansine is a potent maytansine derivative. Experimental Design: Patients with incurable squamous cell carcinoma of the head and neck or esophagus were eligible. Bivatuzumab was given weekly for 3 consecutive weeks by i.v. infusion. One patient was planned to be treated at each dose tier as long as toxicity did not reach grade 2; otherwise, three patients had to be treated until dose-limiting toxicity occurred. Starting dose was 20 mg/m 2 and dose was subsequently escalated in steps of 20 mg/m 2 . Patients without diseaseprogression and not experiencing dose-limiting toxicity were eligible for repeated courses. Blood serum samples were taken throughout the treatment period to determine the pharmacokinetic properties of bivatuzumab mertansine and to assess the human anti^bivatuzumab mertansine antibody response. Results: Seven patients received a total of 23 weekly doses of bivatuzumab mertansine. One patient at the 100 mg/m 2 and one at the 120 mg/m 2 level experienced stable disease during treatment phase but also developed grade 1skin toxicity (desquamation). One of them received a second treatment course. At the highest dose level achieved in this study (140 mg/m 2 ), one patient developed toxic epidermal necrolysis after two infusions and died. Massive apoptosis of skin keratinocytes had occurred, whereas only symptomatic therapy for skin toxicity was available. The riskbenefit assessment of all patients treated in the total phase I program (4 clinical trials, 70 patients) turned out to be negative after consideration of this case of a toxic epidermal necrolysis and the skin-related adverse events observed in the other trials.Therefore, development of the conjugate was discontinued. Interindividual variability in pharmacokinetic variables was low and exposure to BIWI 1 increased proportionally with dose. No anti^bivatuzumab mertansine reactions were observed. Conclusion: The main toxicity of bivatuzumab mertansine was directed against the skin, most probably due to CD44v6 expression in this tissue. The majority of skin reactions was reversible; however, one fatal drug-related adverse event had occurred. Clinical development was discontinued before reaching maximum tolerated dose.

The f15-kDa variable domains of camelid heavy-chainonly antibodies (called Nanobodies) can easily be formatted as multivalent or multispecific single-chain proteins.

Background Low skeletal muscle mass (SMM) is associated with postoperative complications, prolonged hospital stay, and short overall survival (OS) in surgical oncology. We aimed to investigate this association in patients undergoing total laryngectomy (TL). Methods A retrospective study was performed of patients undergoing TL. SMM was measured using CT or MRI scans at the level of the third cervical vertebra (C3). Results In all, 235 patients were included. Low SMM was observed in 109 patients (46.4%). Patients with low SMM had more pharyngocutaneous fistulas (PCFs) than patients with normal SMM (34.9% vs 20.6%; P = .02) and prolonged hospital stay (median, 17 vs 14 days; P < .001). In multivariate analysis, low SMM (hazards ratio, 1.849; 95% confidence interval, 1.202‐2.843) and high N stage were significant prognosticators of decreased OS. Conclusion Low SMM is associated with PCF and prolonged hospital stay in patients undergoing TL. Low SMM is an independent prognostic factor for shorter OS.

No abstract

Purpose The human monoclonal antibody (MAb) fragment L19-SIP is directed against extra domain B (ED-B) of fibronectin, a marker of tumour angiogenesis. A clinical radioimmunotherapy (RIT) trial with 131

This study demonstrates the first-in-human evaluation of a hybrid modality capable of detecting both gamma and fluorescence signals during a surgical procedure. Fluorescence tracing could be performed in ambient light.

Keypoints * Chemo-electroporation therapy with bleomycin is a locoregional treatment modality for head and neck and skin cancer, with the potential to preserve function. * In our institution, chemo-electroporation therapy is used for patients that can no longer be treated by surgery or radiotherapy, or for whom surgical treatment would be very extensive and thus declined by the patient. * This paper describes in detail the technique of bleomycin-electroporation therapy. The literature is reviewed and preliminary results of the clinical trial are presented. * The main focus of the trial is to determine the safety, effectiveness, and burden of bleomycin-electroporation therapy for the patient. * All 17 tumours responded to therapy. Local tumour control was reached in 14 of the 17 (82.4 %) tumours. * Based on the outcome of the clinical trial, bleomycin-electroporation therapy has the potential to become a valuable addition to the late-stage treatment options for patients with head and neck or skin tumours.

Purpose Sentinel lymph node (SLN) biopsy has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). [99mTc]Tc-tilmanocept may be of benefit in OSCC with complex lymphatic drainage patterns and close spatial relation to SLNs. Methods A prospective within-patient evaluation study was designed to compare [99mTc]Tc-tilmanocept with [99mTc]Tc-nanocolloid for SLN detection. A total of 20 patients with early-stage OSCC were included, who underwent lymphoscintigraphy with both tracers. Both lymphoscintigraphic images of each patient were evaluated for SLN detection and radiotracer distribution at 2–4 h post-injection. Results The injection site’s remaining radioactivity was significantly lower for [99mTc]Tc-tilmanocept (29.9%), compared with [99mTc]Tc-nanocolloid (60.9%; p < 0.001). Radioactive uptake in SLNs was significantly lower for [99mTc]Tc-tilmanocept (1.95%) compared with [99mTc]Tc-nanocolloid (3.16%; p = 0.010). No significant difference was seen in SLN to injection site ratio in radioactivity between [99mTc]Tc-tilmanocept (0.066) and [99mTc]Tc-nanocolloid (0.054; p = 0.232). A median of 3.0 and 2.5 SLNs were identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.297). Radioactive uptake in higher echelon nodes was not significantly different between [99mTc]Tc-tilmanocept (0.57%) and [99mTc]Tc-nanocolloid (0.86%) (p = 0.052). A median of 2.0 and 2.5 higher echelon nodes was identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.083). Conclusion [99mTc]Tc-tilmanocept had a higher injection site clearance, but at the same time a lower uptake in the SLN, resulting in an SLN to injection site ratio, which was not significantly different from [99mTc]Tc-nanocolloid. The relatively low-radioactive uptake in SLNs of [99mTc]Tc-tilmanocept may limit intraoperative detection of SLNs, but can be overcome by a higher injection dose.