What side effects are associated with this type of intervention?

Common treatments for dry mouth, such as dietary supplements like d-limonene, generally have a favorable safety profile but can occasionally cause gastrointestinal discomfort or allergic reactions. Other treatments, including topical corticosteroids like fluorometholone and loteprednol, may lead to side effects such as increased intraocular pressure and cataract formation with prolonged use. Cholinergic agonists, such as varenicline nasal spray, can cause nasal irritation and sneezing. Overall, while these treatments can be effective, they may have mild to moderate side effects that should be monitored by a healthcare provider.

What prior FDA approvals exist?

The provided context does not mention specific FDA-approved drugs for the treatment of dry mouth. However, common treatments for dry mouth (xerostomia) often include saliva substitutes, medications like pilocarpine and cevimeline that stimulate saliva production, and various over-the-counter products such as mouthwashes and lozenges. The study of d-limonene, a dietary supplement, for xerostomia relief is an example of exploring alternative therapeutic options beyond conventional medications.

What other types of research exist?

Promising novel alternatives to d-limonene for xerostomia relief include hyaluronic acid vaginal cream, which has shown efficacy in treating vaginal atrophy and may have similar benefits for oral mucosa, and zinc sulfate, which has been studied for taste alterations and may help with dry mouth symptoms. Additionally, artificial tear supplements containing carboxymethylcellulose and hyaluronic acid have been effective for dry eye disease and could potentially be adapted for oral use.

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Alkylating agents

d-Limonene + Radiation + Chemo for Dry Mouth Prevention in Head and Neck Cancer

Phase 1

Recruiting

Led By Quynh-Thu Le

Research Sponsored by Stanford University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically confirmed diagnosis of advanced loco regional squamous cell carcinoma of the nasopharynx, oropharynx, larynx, or hypopharynx scheduled to undergo chemoradiation

Scheduled to receive definitive RT with concurrent platinum-based chemotherapy at Stanford

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 months post completion of chemoradiation

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety of d-limonene, a citrus supplement, for head and neck cancer patients with severe dry mouth. It aims to find the safe dose and see if it can help increase saliva production to ease dry mouth symptoms.

Who is the study for?

This trial is for adults with advanced head and neck squamous cell carcinoma, who are about to receive chemoradiation. They must be able to swallow pills, not have citrus allergies, and women must not be pregnant or breastfeeding. Participants need good liver, kidney, and blood function and a performance status indicating they can care for themselves.

What is being tested?

The study tests if d-Limonene gelcaps can prevent dry mouth in cancer patients undergoing radiation and platinum-based chemotherapy. It also involves completing questionnaires about xerostomia symptoms to assess the effectiveness of the treatment.

What are the potential side effects?

Potential side effects may include typical reactions from chemotherapy like nausea, fatigue, hair loss; radiation-related skin changes; plus any unknown risks associated with d-Limonene since it's being studied as a new use.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a confirmed diagnosis of advanced throat cancer and am scheduled for chemoradiation.

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I am scheduled for radiation and platinum-based chemotherapy at Stanford.

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I can swallow gel capsules.

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I am fully active or can carry out light work.

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My kidney function is good, with creatinine levels low or clearance high.

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My liver is functioning well, with normal bilirubin and enzyme levels.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 months post completion of chemoradiation

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 months post completion of chemoradiation

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 months post completion of chemoradiation for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose limiting Toxicity

Secondary study objectives

Feasibility of adjuvant d-limonene administration

Xerostomia toxicity

Side effects data

From 2012 Phase 3 trial • 256 Patients • NCT01005680

51%

Neutropenia

47%

Leukopenia

46%

Nausea

43%

Vomiting

35%

Anaemia

31%

Decreased appetite

26%

Haemoglobin decreased

26%

Fatigue

25%

Constipation

25%

White blood cell count decreased

24%

Neutrophil count decreased

19%

Alanine aminotransferase increased

13%

Platelet count decreased

12%

Rash

10%

Aspartate aminotransferase increased

10%

Thrombocytopenia

Blood sodium decreased

Hypokalaemia

Insomnia

Pyrexia

Hyponatraemia

Blood creatinine increased

Lymphopenia

Diarrhoea

Dyspepsia

Red blood cell count decreased

Cough

Dizziness

Bone marrow failure

Cerebral infarction

Dyspnoea

Ischaemic stroke

Pulmonary embolism

Embolism venous

Superior vena cava syndrome

100%

80%

60%

40%

20%

Study treatment Arm

Gemcitabine Plus Cisplatin (GC)

Pemetrexed Plus Cisplatin (PC)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

7Treatment groups

Experimental Treatment

Group I: de-escalation dose d-limonene -6gramExperimental Treatment4 Interventions

6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation

Group II: de-escalation dose d-limonene -4gramExperimental Treatment4 Interventions

4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation

Group III: de-escalation dose d-limonene -2gramExperimental Treatment4 Interventions

2 gram d-limonene orally, once daily delivered during chemoradiation

Group IV: d-limonene -8gramExperimental Treatment4 Interventions

8 gram d-limonene orally, as 4 grams 2 times daily delivered during chemoradiation

Group V: d-limonene -6gramExperimental Treatment4 Interventions

6 gram d-limonene orally, as 3 grams 2 times daily delivered during chemoradiation

Group VI: d-limonene -4gramExperimental Treatment4 Interventions

4 gram d-limonene orally, as 2 grams 2 times daily delivered during chemoradiation

Group VII: d-limonene -2gramExperimental Treatment4 Interventions

2 gram d-limonene orally, once daily delivered during chemoradiation

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

D-Limonene Gelcaps

2021

N/A

~180

Cisplatin

2013

Completed Phase 3

~3120

Intensity modulated radiotherapy (IMRT)

2018

N/A

~220

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for dry mouth (xerostomia) include pharmacologic agents like cholinergic agonists, which stimulate saliva production by activating muscarinic receptors in the salivary glands. Topical treatments such as artificial saliva substitutes and mucin stimulators help to lubricate the oral cavity and maintain moisture. Intranasal secretagogues like varenicline nasal spray also increase tear and saliva production by stimulating cholinergic pathways. These treatments are crucial for dry mouth patients as they alleviate discomfort, improve oral health, and enhance quality of life. The dietary supplement d-limonene, being studied for xerostomia relief, may offer a similar benefit by potentially enhancing salivary flow and providing a natural, less invasive option for managing dry mouth symptoms.