Mechanisms of PhotoBioModulation (PBM) focused on oral mucositis prevention and treatment: a scoping review.

BACKGROUND: Oral mucositis (OM) is a severe complication cancer patients undergo when treated with chemoradiotherapy. Photobiomodulation (PBM) therapy also known as low-level laser therapy has been increasingly used for the treatment of such oral toxicity. The aim of this review is to discuss the mechanisms of photobiomodulation (PBM) regarding OM prevention and treatment, and more precisely to focus on the effect of PBM on tumor and healthy cells. METHODS: MEDLINE/PubMed, and google scholar were searched electronically. Selected studies were focusing on PBM effects on tumor and healthy cells. RESULTS: PBM interactions with the tissue and additional mechanism in OM therapy were detailed in this review. Moreover, this review highlighted a controversy about the carcinogenic effect of PBM. Indeed, Many studies reported that PBM could enhance malignant cell proliferation; suggesting that PBM would have no protective effect. In addition to acting on cancer cells, PBM may damage healthy cells. CONCLUSION: More prospective studies are needed to assess the effect of PBM on cancer cells in order to improve its use for OM prevention and treatment.

Photobiomodulation by a new optical fiber device: analysis of the in vitro impact on proliferation/migration of keratinocytes and squamous cell carcinomas cells stressed by X-rays.

Photobiomodulation-based (PBM-based) therapies show promising results in mucositis and dermatitis treatment by stimulating wound healing mechanisms such as cell proliferation and migration. The aim of the present study is to investigate the in vitro effects of CareMin650 on the proliferation and migration of two different types of cells, namely cancer and non-cancer cells, with or without X-ray radiation. Study design used PBM through a combination of 0-3-6 J/cm2 doses-with or without X-ray radiation-on the proliferation and migration capabilities of a keratinocyte cell line (HaCaT) and a squamous cell carcinoma line (SCC61). PBM is delivered by a new woven optical fiber device, namely CareMin650 prototype (light emission by LEDs (light-emitting diodes), peak at 660 nm, irradiance of 21.6 mW/cm2). The effectiveness of PBM to increase HaCaT proliferation and migration (with or without X-ray radiation) supports the capability of PBM to favor wound healing. It also highlights that PBM does not provide any anti-radiation effect to previously X-rays radiated SCC (p < 0.001). Such data supports the beneficial effect of PBM delivered by an optical fiber device to heal wounds, without promoting cancer development.

EVESOR, a model-based, multiparameter, Phase I trial to optimize the benefit/toxicity ratio of everolimus and sorafenib.

AIM: This novel multiparameter Phase I study aimed to optimize doses/dosing schedules of everolimus and sorafenib drug combination, based on modeling/simulation (NCT01932177). PATIENTS & METHODS: About 26 patients with solid tumors were treated in four different dosing schedules. Everolimus once daily + sorafenib twice daily were given continuously in arms A and B, and intermittently in arms C (alternating every other week) and D (everolimus continuous and sorafenib 3 days on/4 days off). RESULTS: Continuous schedules exhibited higher toxicity risks than intermittent schedules (64.1 vs 35.9%; p < 0.0001), and trends for lower disease control rates (80 vs 100%). No significant pharmacokinetic interaction was identified. CONCLUSION: Feasibility of EVESOR trial is demonstrated. Intermittent schedules might provide better tolerance and efficacy than continuous schedules.

Multiparameter Phase I trials: a tool for model-based development of targeted agent combinations--example of EVESOR trial.

Optimal development of targeted drug combinations is one of the future challenges to be addressed. Computerization and mathematical models able to describe biological phenomena and to simulate the effects of changes in experimental conditions may help find solutions to this issue. We propose the concept of 'multiparameter trials', where biological, radiological and clinical data required for modeling purpose are collected and illustrated by the ongoing academic EVESOR trial. The objective of the model-based work would be the determination of the optimized doses and dosing schedules of everolimus and sorafenib, offering the maximization of the predicted modeled benefit/toxicity ratio in patients with solid tumors. It may embody the 'proof of concept' of model-based drug development of anticancer agent combinations.