Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment

Purpose The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the prevention and treatment of oral mucositis (OM) in patients treated with concurrent radiation and systemic treatment for head and neck cancer. Methods Randomized, phase II, double-blind, placebo-controlled trial (1:1 ratio) of 3% melatonin oral gel mouthwashes vs. placebo, during IMRT (total dose ≥ 66 Gy) plus concurrent Q3W cisplatin or cetuximab. Primary endpoint: grade 3–4 OM or Severe Oral Mucositis (SOM) incidence by RTOG, NCI, and a composite RTOG-NCI scales. Secondary endpoints: SOM duration and grade 2–4 OM or Ulcerative Oral Mucositis (UOM) incidence and duration. Results Eighty-four patients were included in the study. Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Compared with the placebo arm, RTOG-defined SOM incidence was numerically lower in the 3% melatonin oral gel arm (53 vs. 64%, P = 0.36). In patients treated with cisplatin, assessed by the RTOG-NCI composite scale, both SOM incidence (44 vs. 78%; P = 0.02) and median SOM duration (0 vs. 22 days; P = 0.022) were significantly reduced in the melatonin arm. Median UOM duration assessed by the RTOG-NCI scale was also significantly shorter in the melatonin arm (49 vs. 73 days; P = 0.014). Rate of adverse events and overall response rate were similar between the two arms. Conclusions Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial (AU)

Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment.

PURPOSE: The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the prevention and treatment of oral mucositis (OM) in patients treated with concurrent radiation and systemic treatment for head and neck cancer. METHODS: Randomized, phase II, double-blind, placebo-controlled trial (1:1 ratio) of 3% melatonin oral gel mouthwashes vs. placebo, during IMRT (total dose ≥ 66 Gy) plus concurrent Q3W cisplatin or cetuximab. Primary endpoint: grade 3-4 OM or Severe Oral Mucositis (SOM) incidence by RTOG, NCI, and a composite RTOG-NCI scales. Secondary endpoints: SOM duration and grade 2-4 OM or Ulcerative Oral Mucositis (UOM) incidence and duration. RESULTS: Eighty-four patients were included in the study. Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Compared with the placebo arm, RTOG-defined SOM incidence was numerically lower in the 3% melatonin oral gel arm (53 vs. 64%, P = 0.36). In patients treated with cisplatin, assessed by the RTOG-NCI composite scale, both SOM incidence (44 vs. 78%; P = 0.02) and median SOM duration (0 vs. 22 days; P = 0.022) were significantly reduced in the melatonin arm. Median UOM duration assessed by the RTOG-NCI scale was also significantly shorter in the melatonin arm (49 vs. 73 days; P = 0.014). Rate of adverse events and overall response rate were similar between the two arms. CONCLUSIONS: Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial.

Activity of weekly paclitaxel-cetuximab chemotherapy in unselected patients with recurrent/metastatic head and neck squamous cell carcinoma: prognostic factors

Background. Standard treatment for recurrent/metastatic head and neck squamous cell carcinoma (RM-SCCHN) is based in on platinum and cetuximab combination therapy. Unfortunately, not all patients are candidates to receive platinum-based treatment, because of different conditions as comorbidity and poor performance status. Weekly paclitaxel and cetuximab (WPC) is an active therapeutic alternative, based on a phase II study, with less toxicity. Our main objective is to confirm its activity in unselected patients, mostly unfit for aggressive therapies, analysing also some clinically relevant prognostic factors (PFs). Methods. Retrospective data was collected for RM-SCCHN patients, treated at our institution between January 2008 and July 2014 with weekly paclitaxel (80 mg/m2) and cetuximab (400/250 mg/m2). Results. 148 patients were treated. The objective response rate (OR) was as follows: 13 patients (8.78%) complete response (CR); 57 patients (38.51%) partial response (PR) and 30 patients (20.3%) stable disease (SD). Median overall survival (OS) was 10 months (95% CI 8.31-11.69) and median progression free survival (PFS) was 7 months (95% CI 5.88-8.12). Response to treatment showed independent prognosis relevance as PF in multivariate analysis for PFS and OS. Furthermore, decline in serum magnesium during the treatment was also an independent PF for OS. Conclusions. WPC activity was confirmed as a useful therapy on real-life unselected RM-SCCHN patients, with similar benefit to that obtained in the phase II study, and comparable to platinum and cetuximab based treatment, confirming its value in unfit patients. In addition to treatment response, a change in serum magnesium values during treatment was proved as independent PF on OS (AU)

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Activity of weekly paclitaxel-cetuximab chemotherapy in unselected patients with recurrent/metastatic head and neck squamous cell carcinoma: prognostic factors.

BACKGROUND: Standard treatment for recurrent/metastatic head and neck squamous cell carcinoma (RM-SCCHN) is based in on platinum and cetuximab combination therapy. Unfortunately, not all patients are candidates to receive platinum-based treatment, because of different conditions as comorbidity and poor performance status. Weekly paclitaxel and cetuximab (WPC) is an active therapeutic alternative, based on a phase II study, with less toxicity. Our main objective is to confirm its activity in unselected patients, mostly unfit for aggressive therapies, analysing also some clinically relevant prognostic factors (PFs). METHODS: Retrospective data was collected for RM-SCCHN patients, treated at our institution between January 2008 and July 2014 with weekly paclitaxel (80 mg/m2) and cetuximab (400/250 mg/m2). RESULTS: 148 patients were treated. The objective response rate (OR) was as follows: 13 patients (8.78%) complete response (CR); 57 patients (38.51%) partial response (PR) and 30 patients (20.3%) stable disease (SD). Median overall survival (OS) was 10 months (95% CI 8.31-11.69) and median progression free survival (PFS) was 7 months (95% CI 5.88-8.12). Response to treatment showed independent prognosis relevance as PF in multivariate analysis for PFS and OS. Furthermore, decline in serum magnesium during the treatment was also an independent PF for OS. CONCLUSIONS: WPC activity was confirmed as a useful therapy on real-life unselected RM-SCCHN patients, with similar benefit to that obtained in the phase II study, and comparable to platinum and cetuximab based treatment, confirming its value in unfit patients. In addition to treatment response, a change in serum magnesium values during treatment was proved as independent PF on OS.

Dolor irruptivo oncológico inducido por radioterapia: ¿es posible optimizar su tratamiento? / Radiotherapy-induced breakthrough cancer pain: is it possible to optimize its treatment?

Introducción: en el contexto de la radioterapia, el control del dolor irruptivo oncológico (DIO) supone un reto especial. El DIO ha sido definido por la Sociedad Española del Dolor (SED), la Sociedad Española de Oncología Médica (SEOM) y la Sociedad Española de Cuidados Paliativos (SECPAL) como una exacerbación del dolor súbita y transitoria, de gran intensidad (EVA > 7) y de corta duración (inferior a 20-30 minutos), que aparece sobre la base de un dolor persistente estable cuando este se encuentra reducido a un nivel tolerable (EVA < 5) mediante el uso de opioides mayores. Objetivos: el objetivo principal de este estudio fue evaluar la intensidad del DIO inducido por tratamientos oncológicos que incluyeran radioterapia (RT), tanto exclusiva como asociada a quimioterapia (RT/QT). Secundariamente, se evaluó la eficacia del tratamiento con fentanilo sublingual pautado para el control del DIO. Material y métodos: estudio observacional retrospectivo realizado en 110 pacientes reclutados en 19 Servicios de Radioterapia españoles. Los pacientes debían presentar DIO inducido por RT o RT/QT, con o sin medicación pautada y cuya intensidad fuera de una EVA > 6 en las últimas 24-48 h. Se establecieron controles en el momento basal, y a los 3, 7, 15 y 30 días. Resultados: se apreció un descenso en la media de los valores en la escala EVA según avanzó el estudio (EVA = 6 en el control 0 a EVA = 3 en el control 3), y las diferencias fueron significativas (p < 0,0001). La satisfacción con el tratamiento fue calificada como buena o excelente por el 85,3% de los pacientes y por el 92,7% de los investigadores. Conclusiones: los resultados de este estudio demuestran la eficacia del tratamiento del DIO con fentanilo sublingual en el contexto del tratamiento oncológico radioterápico, con un descenso significativo en los valores EVA frente al valor basal. La elevada satisfacción de los médicos y pacientes con este tratamiento refleja la eficacia y la comodidad del fentanilo sublingual en el control del DIO (AU)

Introduction: In the context of radiotherapy, control of breakthrough cancer pain (BTPc) is particularly challenging. BTPc has been defined by the Spanish Society of Pain (SED), the Spanish Society of Medical Oncology (SEOM) and the Spanish Society for Palliative Care (SECPAL) as a sudden and transient exacerbation of pain of great intensity (VAS > 7) and short (less than 20-30 minutes), which appears on the basis of a stable persistent pain when it is reduced to a tolerable level (VAS < 5) by using major opioids. Objectives: The main objective of this study was to assess the intensity of BTPc induced by cancer treatments that included radiotherapy (RT), both exclusive and associated with chemotherapy (RT/CT). Secondly, the efficacy of treatment was evaluated with fentanyl sublingual scheduled for BTPc control. Material and methods: Retrospective, observational study in 110 patients recruited in 19 Spanish Radiotherapy Services. Patients must have BTPc induced by RT or RT/CT, with or without medication prescribed and with an intensity outside a VAS > 6 in the last 24-48 h. Controls were established at baseline and at 3, 7, 15 and 30 days. Results: There was a decrease in mean values on the VAS scale as the study progressed (VAS = 6 in the control 0 to VAS = 3 in the control 3) and the differences were significant (p < 0.0001). Treatment satisfaction was rated as good or excellent by 85.3% of patients and 92.7% of researches. Conclusions: The results of this study demonstrate the efficacy of BTPc treatment with sublingual fentanyl in the context of the radiotherapy cancer treatment, with a significant decrease in VAS from baseline values . The high satisfaction among physicians and patients with this treatment reflects the efficacy and convenience of sublingual fentanyl in controlling BTPc (AU)

Novel antiangiogenic therapies against advanced hepatocellular carcinoma (HCC).

Angiogenesis is a cornerstone in the process of hepatocarcinogenesis. In the sorafenib era, other antiangiogenic targeted drugs, such as monoclonal antibodies and a new generation of tyrosine kinase inhibitors, have been shown in phase II trials to be safe and effective in the treatment of advanced hepatocellular carcinoma. Several currently active phase III trials are testing these drugs, both in first- and second-line settings. Strategies to overcome primary and acquired resistance to antiangiogenic therapy are urgently needed. Novel biomarkers may help in improving the efficacy of drugs targeting angiogenesis.

Novel antiangiogenic therapies against advanced hepatocellular carcinoma (HCC)

Angiogenesis is a cornerstone in the process of hepatocarcinogenesis. In the sorafenib era, other antiangiogenic targeted drugs, such as monoclonal antibodies and a new generation of tyrosine kinase inhibitors, have been shown in phase II trials to be safe and effective in the treatment of advanced hepatocellular carcinoma. Several currently active phase III trials are testing these drugs, both in first- and second-line settings. Strategies to overcome primary and acquired resistance to antiangiogenic therapy are urgently needed. Novel biomarkers may help in improving the efficacy of drugs targeting angiogenesis (AU)