pectins and Head-and-Neck-Neoplasms

PD-1/PD-L1 engagement and overexpression of galectin-3 (Gal-3) are critical mechanisms of tumor-induced immune suppression that contribute to immunotherapy resistance. We hypothesized that Gal-3 blockade with belapectin (GR-MD-02) plus anti-PD-1 (pembrolizumab) would enhance tumor response in patients with metastatic melanoma (MM) and head and neck squamous cell carcinoma (HNSCC).. We performed a phase I dose escalation study of belapectin+pembrolizumab in patients with advanced MM or HNSCC (NCT02575404). Belapectin was administered at 2, 4, or 8 mg/kg IV 60 min before pembrolizumab (200 mg IV every 3 weeks for five cycles). Responding patients continued pembrolizumab monotherapy for up to 17 cycles. Main eligibility requirements were a functional Eastern Cooperative Oncology Group status of 0-2, measurable or assessable disease, and no active autoimmune disease. Prior T-cell checkpoint antibody therapy was permitted.. Objective response was observed in 50% of MM (7/14) and and 33% of HNSCC (2/6) patients. Belapectin+pembrolizumab was associated with fewer immune-mediated adverse events than anticipated with pembrolizumab monotherapy. There were no dose-limiting toxicities for belapectin within the dose range investigated. Significantly increased effector memory T-cell activation and reduced monocytic myeloid-derived suppressor cells (M-MDSCs) were observed in responders compared with non-responders. Increased baseline expression of Gal-3+ tumor cells and PD-1+CD8+ T cells in the periphery correlated with response as did higher serum trough levels of pembrolizumab.. Belapectin+pembrolizumab therapy has activity in MM and HNSCC. Increased Gal-3 expression, expansion of effector memory T cells, and decreased M-MDSCs correlated with clinical response. Further investigation is planned.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Blood Proteins; Female; Galectins; Head and Neck Neoplasms; Humans; Immune Checkpoint Inhibitors; Male; Memory T Cells; Middle Aged; Multiple Myeloma; Myeloid-Derived Suppressor Cells; Pectins; Programmed Cell Death 1 Receptor; Squamous Cell Carcinoma of Head and Neck; Time Factors; Treatment Outcome

The aim of the current analysis was to evaluate the effectiveness and tolerability of rapid onset opioid in a cohort of head and neck cancer (HNC) patients affected by painful mucositis influencing swallowing function during RT ± ChT with definitive or adjuvant intent.. A retrospective analysis was conduct on HNC patients during RT ± ChT that received fentanyl pectin na sal spray (FPNS) for incidental BTP due to painful mucositis 13 min before the main meals. The period of observation has been 90 days starting from the beginning of RT ± ChT.. Forty HNC patients with incidental BTP due to painful mucositis treated with FPNS were analyzed. The mean NRS of untreated episodes of BTP was 5.73 ± 1.54 decreasing to 2.25 ± 2.45 with FPNS (median dose 100 mcg). During the pain treatment, the number of meals increased from 2.08 ± 0.35 to 2.868 ± 0.4 (p = 0.000), and the BMI remained stable (from 25.086 ± 3.292 to 25.034 ± 3.090; p = 0.448). The 94.9% of patients was satisfied or very satisfied for the rapidity of the effect, and 97.4% for the easiness and convenience in the use.. FPNS showed an acceptable safety activity profile in predictable BTP due to painful mucositis in HNC patients during RT ± ChT. FPNS was also effective in reducing the mucositis sequelae and allowing the completion of RT scheduled scheme. Moreover, patients declared satisfaction in terms of ease of use.

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Antineoplastic Agents; Breakthrough Pain; Cisplatin; Female; Fentanyl; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mucositis; Nasal Sprays; Pain Management; Pectins; Radiotherapy, Intensity-Modulated; Retrospective Studies

Painful mucositis is one of the most distressing toxicities of chemoradiotherapy (CRT) for head and neck cancer (HNC), with the characteristics of incidental predictable breakthrough pain (BTP) during swallowing. Fentanyl pectin nasal spray (FPNS) could be a good therapeutic option.. Patients were prospectively considered if receiving basal analgesic therapy with opiates for painful mucositis of grade ⩾4 on a numerical rating scale from 0 to 10. They were offered FPNS 100mcg before oral intake. When patients reached the effective dose, they evaluated the basal pain intensity before FPNS use and after 10, 20, 30 and 40min.. Seventeen HNC patients were offered FPNS before oral intake, with 15 patients completing treatment. Mean reduction of incidental BTP intensity after FPNS was 3.1 points (range 1.2-5.8). Mean time elapsed since FPNS use and highest pain reduction was 26min.. FPNS demonstrated activity against BTP when swallowing in HNC patients. These data should be considered as hypothesis-generating.

Topics: Administration, Inhalation; Adult; Aged; Analgesics, Opioid; Breakthrough Pain; Combined Modality Therapy; Female; Fentanyl; Head and Neck Neoplasms; Humans; Male; Middle Aged; Pectins; Stomatitis