Endoscopic Injection of Mitomycin C for the Treatment of Pharyngoesophageal Stenosis

Endoscopic Injection of Mitomycin C for the Treatment of Pharyngoesophageal Stenosis Refractory to Endoscopic Treatment With Dilatation in Patients With Head and Neck Cancer

Management of pharyngoesophageal stenosis (PES) in patients after head and neck cancer (HNC) treatment remains a challenge. There are some cases of strictures refractory to dilation sessions. This study aimed to evaluate the efficacy of Mitomycin C (MMC) endoscopic injection for the treatment of refractory pharyngoesophageal stenosis.

Patients and methods: This is a prospective study in patients with dysphagia following head and neck cancer treatment, without evidence suggestive of tumor recurrence, and refractory to endoscopic treatment. Theses undergo endoscopic dilation of the stenotic segment with thermoplastic bougies, followed by the injection of MMC.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Neoplasms; Esophageal Neoplasms; Deglutition Disorders; Esophageal Stenosis
• Intervention / Treatment: Drug: Endoscopic injection of Mitomycin C

Detailed Description

Management of pharyngoesophageal stenosis (PES) after cancer treatment in patients with head and neck cancer (HNC) remains a challenge. The etiology of PES in this group of patients is probably multifactorial, being associated with surgical manipulation, ischemic effects of radiotherapy and even cancer recurrence. It is estimated that up to 50% of patients treated for advanced HNC will present some degree of dysphagia. PES is a frequent cause of post treatment dysphagia of HNC patients. Although the exact prevalence is unknown, several retrospective series estimate that upper cervical stricture is present in 1% to 23% of the cases. The initial approach to PES is endoscopic dilation with a reported success rate ranging from 76% to 96%. In patients with refractory strictures to dilation sessions, endoscopic corticosteroid injection, such as triamcinolone, is usually added to the dilation sessions, which may increase the success of the endoscopic treatment. A relatively small group of patients will be refractory to the association of dilation and corticosteroid injection treatment. Metal stents may be considered in this scenario, but in the case of pharyngoesophageal stenosis, this approach is limited by cervical pain and foreign body sensation. Surgical reconstruction for pharyngoesophageal stenosis refractory to endoscopic treatment is the last therapeutic option (2). Previous radiotherapy, eventual reconstruction with cutaneous flaps make a surgical manipulation of the cervical region a real challenge, with increased adverse event rate, including restenosis.(2) Because of such difficulties, this prospective study aimed to evaluate the efficacy of Mitomycin C (MMC) endoscopic injection for the treatment of pharyngoesophageal stenoses in patients who were treated for head and neck cancer, refractory to endoscopic dilation treatment. There are descriptions of the use of Mitomycin C for scar prevention after ophthalmologic and otorhinolaryngological interventions (8). Its use in endoscopy has previously been described for the treatment of laryngeal and tracheal stenosis as well as refractory esophageal stenosis. Mitomycin C is a substance isolated from the bacterium Streptomyces caespitosus, which is used as a chemotherapeutic agent and has antiproliferative effects on fibroblasts, reducing fibroblast proliferation and collagen formation. Some studies demonstrated the ability to decrease fibroblast activity and consequent scar formation after the application of Mitomycin C on culture of fibroblasts in low concentrations (0.1 to 0.4 mg / ml) for 5 to 10 minutes, affecting their proliferation for over 3 weeks.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01246-000
    • Instituto do Cancer do Estado de Sao Paulo - ICESP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with dysphagia following head and neck cancer treatment
• Patients without endoscopic or radiological evidence suggestive of tumor recurrence
• Patients refractory to endoscopic treatment

Exclusion Criteria:

• Endoscopic or radiological signs suggestive of tumor recurrence

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Endoscopic injection of Mitomycin C; Endoscopy injection of Mitomycin C will be perform to the treatment of pharyngoesophageal stenosis refractory to endoscopic treatment with dilatation in patients with head and neck cancer	Drug: Endoscopic injection of Mitomycin C; administration included dilation of the stenotic segment with thermoplastic bougies, followed by the injection of 3mg of Mitomycin C, divided into 4 aliquots of 0.75mg, injected in the four quadrants, at the stenosis level.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
dysphagia	dysphagia score (0 = able to eat normal diet / no dysphagia;1 = able to swallow some solid foods; 2 = able to swallow only semi solid foods; 3 = able to swallow liquids only; 4 = unable to swallow anything / total dysphagia)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of sessions of endoscopic dilations	decrease in the number of sessions of endoscopic dilations	2 years

Collaborators and Investigators

• Sponsor: Fauze Maluf Filho

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2015
• Primary Completion (Actual): May 5, 2015
• Study Completion (Actual): January 5, 2018

Study Registration Dates

• First Submitted: March 22, 2018
• First Submitted That Met QC Criteria: May 17, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Actual): May 30, 2018
• Last Update Submitted That Met QC Criteria: May 17, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Endoscopic injection of Mitomycin C
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Esophageal Diseases; Neoplasms; Head and Neck Neoplasms; Deglutition Disorders; Constriction, Pathologic; Esophageal Neoplasms; Esophageal Stenosis; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Mitomycins; Mitomycin
• Other Study ID Numbers: NP549/14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No