Squamous Cell Carcinoma of Hypopharynx, Squamous Cell Carcinoma of Nasopharynx, Squamous Cell Carcinoma of Oropharynx
Conditions
Keywords
Oral mucositis, Low Level Laser Therapy, Head and neck cancer
Brief summary
Oral mucositis remains a limiting factor in in head and neck squamous cell carcinomas patients treated with chemoradiation leading to pain, dysphagia, and weight loss. Low-level laser therapy emerges as a promising, preventive therapy of chemoradiation-induced OM. This study was designed to assess the efficacy of Low Level Laser Therapy (LLLT) in reducing the incidence and/or severity of oral mucositis.
Detailed description
Assuming oral mucositis grade 3 for placebo 0.4 (P0); laser group 0.15 (P1) ; β=0.2; α=0.05, sample size was 94 pts. From Jun 2007 to Dec 2010, 47 laser group and 47 placebo patients bearer of head and neck squamous cell carcinomas of nasopharynx, oropharynx and hypopharynx entered a prospective, randomized, double blind, placebo-controlled, phase III trial. chemoradiotherapy consisted of conventional radiotherapy 70.2 Gray (Gy) (1.8Gy/d, 5 times/wk) + concurrent cisplatin 100 mg/m2 every 3 weeks. The primary end point was the incidence of grade 3-4 oral mucositis. The Low-level laser therapy used daily, was a diode indium phosphide, gallium and aluminum (InGaAlP), 660nm-100 milliwatts (mW)-4 Joules (J)/cm²(DMC, São Carlos, São Paulo, Brazil). Oral mucositis evaluation was done by WHO and Oral Mucositis Assessment Scale (OMAS) scale.
Interventions
DEVICELow Level Laser Therapy- (DMC, São Paulo, Brazil)
Diode laser (DMC,São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100 mW, 4J/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.
DEVICEPlacebo (DMC, São Paulo, Brazil)
The placebo (DMC, São Paulo, Brazil) was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light.
Sponsors
Instituto Nacional de Cancer, Brazil
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Histological diagnosis of squamous cell carcinoma (nasopharynx, oropharynx and hypopharynx) * Candidates for surgery or treatment for organ preservation * Performance status (PS) of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) * Indication for radiotherapy and concurrent platinum-based chemotherapy * Oral mucosa intact * Agree to follow the protocol of oral hygiene * Informed consent.
Exclusion criteria
* Patients using medication for treatment and or prevention of mucositis * Patients incapable of treatment compliance or of performing the protocol of oral hygiene
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and / or Severity of Oral Mucositis | 7 weeks | The oral cavities of all patients were evaluated daily, from the first day until the last day of treatment. We used the scales of mucositis of the World Health Organization (WHO) and the Oral Mucositis Assessment Scale (OMAS) and a visual analogue scale (VAS) for pain assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oral Mucositis Survival Free, Pain, Opioid Treatment, Hospitalization, Treatment Interruption, Treatment Delay, Patient Weight Loss, Nasogastric Tube or of a Gastrostomy. | 7 weeks | Oral mucositis survival free, pain, opioid treatment, hospitalization, treatment interruption, treatment delay, patient weight loss, nasogastric tube or of a gastrostomy.The oral cavities of all patients were evaluated, from the first day to the last day of treatment. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light.
Placebo (DMC, São Paulo, Brazil): The placebo (DMC, São Paulo, Brazil) was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.Patients in the placebo group received the same treatment during the same time, but in this case the laser tip produced no light. | 47 |
| Low Level Laser Therapy The investigators used a diode laser (DMC, São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100 mW, 4J/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region.
Low Level Laser Therapy- (DMC, São Paulo, Brazil): Diode laser (DMC,São Paulo, Brazil) InGaAlP (indium phosphide, gallium and aluminum), with 100 mW, 4J/cm ², with an area of 0.24 cm ². The laser was daily applied by a dentist and touched the mucosa of the lips, right and left buccal mucosa, left and right lateral tongue border, buccal floor and ventral tongue, totaling nine points per region. | 47 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | missing consultation | 9 | 8 |
Baseline characteristics
| Characteristic | Placebo | Low Level Laser Therapy | Total |
|---|---|---|---|
| Age, Continuous | 55.7 years STANDARD_DEVIATION 8.6 | 53.5 years STANDARD_DEVIATION 6.9 | 54.6 years STANDARD_DEVIATION 7.7 |
| Region of Enrollment Brazil | 47 participants | 47 participants | 94 participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 40 Participants | 42 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 47 | 10 / 47 |
| serious Total, serious adverse events | 17 / 47 | 15 / 47 |
Outcome results
Primary
Incidence and / or Severity of Oral Mucositis
The oral cavities of all patients were evaluated daily, from the first day until the last day of treatment. We used the scales of mucositis of the World Health Organization (WHO) and the Oral Mucositis Assessment Scale (OMAS) and a visual analogue scale (VAS) for pain assessment.
Time frame: 7 weeks
Population: Data related to the primary endpoint were handled in a per protocol treatment analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Incidence and / or Severity of Oral Mucositis | 19 Grade 3-4 oral mucositis |
| Low Level Laser Therapy | Incidence and / or Severity of Oral Mucositis | 3 Grade 3-4 oral mucositis |
Comparison: The primary end point of the study was the incidence of grade 3-4 oral mucositis (OM) according to the WHO scale. Assuming an α =0.05 and a β = 0.20, with the estimates of proportion being 0.40 for placebo (P0) and 0.15 for LLLT (P1) a total of 94 patients were evaluated. One-sided test error was the basis for the sample size determination and all the reported P-values were derived from two-sided statistical tests. P-values less than or equal to 0.05 were considered statistically significant.p-value: 0.0595% CI: [0.05, 0.498]Chi-squared
Secondary
Oral Mucositis Survival Free, Pain, Opioid Treatment, Hospitalization, Treatment Interruption, Treatment Delay, Patient Weight Loss, Nasogastric Tube or of a Gastrostomy.
Oral mucositis survival free, pain, opioid treatment, hospitalization, treatment interruption, treatment delay, patient weight loss, nasogastric tube or of a gastrostomy.The oral cavities of all patients were evaluated, from the first day to the last day of treatment.
Time frame: 7 weeks