Oral rinses containing calcium and phosphate have been studied in patients with cancer for effects on oral mucositis.
Caphosol is a calcium phosphate solution resembling human saliva that is intended to replace the normal ionic and pH balance in the oral cavity. It has been used as a mouth rinse to moisten, lubricate, and clean the oral mucosa, tongue, and throat. Caphosol has been evaluated for mucositis.
McGuire, D.B., Fulton, J.S., Park, J., Brown, C.G., Correa, M.E.P., Eilers, J., . . . Lalla, R.V. (2013). Systematic review of basic oral care for the management of oral mucositis in cancer patients. Supportive Care in Cancer, 21, 3165–3177.
STUDY PURPOSE: To systematically review oral care interventions for the prevention and treatment of oral mucositis (OM) in patients undergoing cancer treatment
TYPE OF STUDY: Systematic review
DATABASES USED: Ovid MEDLINE
KEYWORDS: mucositis, stomatitis, cancer, oral care, oral care protocol, dental care, dental cleaning, oral decontamination, oral hygiene, saline, sodium bicarbonate, baking soda, chlorhexidine, magic/miracle mouthwash, calcium phosphate
INCLUSION CRITERIA: Primary research article, reflects a variety of research designs, rested the effects of intervention on severity of OM or mucositis-related symptoms
EXCLUSION CRITERIA: Review articles, clinical case reports, literature reviews, non-research articles
TOTAL REFERENCES RETRIEVED = 129
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Hadorn et al. criteria was used to assess the flaws in the selected publications, and levels of evidence were rated using the Somerfield schema.
FINAL NUMBER STUDIES INCLUDED = 52
SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: Not stated
PHASE OF CARE: Active antitumor treatment
The guidelines are as follows.
Oral care protocols are recommended to patients for the prevention and treatment of OM. Chlorhexidine is not recommended for patients with head and neck cancer who receive radiotherapy treatment.
Evidence for interventions to prevent and treat OM are limited, making guideline recommendations difficult.
Nurses should teach patients appropriate oral care to help prevent OM.
Quinn, B. (2013). Efficacy of a supersaturated calcium phosphate oral rinse for the prevention and treatment of oral mucositis in patients receiving high-dose cancer therapy: A review of current data. European Journal of Cancer Care, 22, 564–579.
To summarize the literature on calcium phosphate oral rinse for the prevention and treatment of oral mucositis (OM)
Caphosol was found to reduce OM grade, duration, or both in 24 out of 30 studies. Caphosol was associated with a reduction in OM-associated pain in 14 of 17 studies with more than 30 patients and 6 studies with fewer than 30 subjects. Data regarding nutrition, patient compliance, and length of hospitalization were conflicting, but the majority demonstrated a benefit with Caphosol. Two studies reported potential cost savings with the use of Caphosol. Three studies with 30 patients and three single-center studies with controls of standard mouth care and MuGard® did not find significant differences in OM grade or duration. Two studies of more than 30 patients did not demonstrate a benefit associated with OM-related pain. One study did not find a significant difference in nausea or dysphasia for Caphosol-treated patients. Three studies failed to demonstrate any differences in length of stay.
The majority of the studies included in the review reported some benefit from Caphosol use. The data demonstrate the opportunity to further study the role of supersaturated calcium phosphate oral rinse in the prevention and treatment of OM.
The effects from OM remain a significant challenge for patients receiving cancer treatment. Nursing involvement in prospective, randomized, blinded studies could provide the best practice data needed to recommend treatments for OM. The limitations for the studies included in this review are significant and do not provide rigorous scientific support for the use of Caphosol.
Lambrecht, M., Mercier, C., Geussens, Y., & Nuyts, S. (2013). The effect of a supersaturated calcium phosphate mouth rinse on the development of oral mucositis in head and neck cancer patients treated with (chemo)radiation: A single-center, randomized, prospective study of a calcium phosphate mouth rinse + standard of care versus standard of care. Supportive Care in Cancer, 21, 2663–2670.
To investigate whether the addition of a neutral, supersaturated, calcium phosphate (CP) mouth rinse benefits the severity and duration of acute mucositis in patients with head and neck cancer treated with (chemo)radiation
Patients in group A were instructed to use caphosol mouth rinse twice daily with 15 ml solution for one minute plus standard care. Patients in group B were instructed to use standard care consisting of gargling with 15 ml of “magic mouth wash” (hydrocortisone, lidocaine, nystatin, propylene glycol, sodium carboxymethylcellulose, aqua admixture) up to six times per day, swallowing one time out of two. Two experienced physicians conducted visual inspection of the oral cavity and visualized oropharyns weekly until two to seven weeks after completion or until mucositis grade 1 or 0.
PHASE OF CARE: Active antitumor treatment
No significant differences were found in grade, time of onset, or duration of peak mucositis between groups. Fewer patients in the study arm experienced grade 3 or higher mucositis (59% versus 71%). Mean time to development of mucositis was 28.6 days in the study group versus 28.7 days in the control group (p = .96). Duration of mucositis was 22.7 days in the study group versus 24.6 days in the control group (p = .62). No significant reduction in the need for analgesics was found.
An oral solution of neutral CP mouth rinse does not reduce frequency, duration, or severity of oral mucositis or pain in patients treated with (chemo)radiation for head and neck cancer. No evidence supports its standard use.
Mucosal damage continues to be an important and debilitating side effect that warrants continued research.
Markiewicz, M., Dzierzak-Mietla, M., Frankiewicz, A., Zielinska, P., Koclega, A., Kruszelnicka, M., & Kyrcz-Krzemien, S. (2012). Treating oral mucositis with a supersaturated calcium phosphate rinse: comparison with control in patients undergoing allogeneic hematopoietic stem cell transplantation. Supportive Care in Cancer, 20, 2223–2229.
To evaluate the efficacy of supersaturated calcium phosphate rinse (SCPR) with customary care (topical mouth solutions) on measures of severity and consequent interventions and complications
In the treatment group, patients rinsed their mouths four times daily with the SCPR. In the control group, patients received customary topical mouth care with the extract of salvia leaves (twice daily), providone-iodine mouth solution (1% water solution of iodide with polyvinylpyrrolidone) once daily, and fluconazole mouth solution (50 mg fluconazole, 50 mg glycerine, 10 g vitamin A, and 10 g vitamin E with or without 2.5 g benzociaine) twice daily.
The SCPR treatment was administered from the first day of conditioning until patients reached the absolute neutrophil count of greater or equal to 0.2 g/l (a value that was considered an indication of the beginning of neutrophil recovery). Patients self-assessed the level of pain in the mouth and pharynx using a 0–10 visual analog scale (VAS) and measured swallowing problems using a 0–5 VAS.
The same experienced hematologist performed a physical examination of the oral cavity each day throughout the study, ranking cases according to the World Health Organization (WHO) scale for grading oral toxic effects of cancer treatment.
This was a single-site study conducted in an inpatient setting. The study was conducted at the Department of Hematology and Bone Marrow Transplantation at the Medical University of Silesia in Katowice, Poland, in 2009.
This was a prospective randomized, non-blinded, controlled trial with 40 consecutive patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Half of the patients received treatment with the supersaturated rinse, and the remaining half received customary care with topical mouth solutions. Patients enrolled in this study underwent transplantation in the Medical University of Silesia in Katowice, Poland, in 2009.
The World Health Organization scale (WHO) was used to measure severity of mucositis. Duration was recorded in days. Peak mean pain in mouth was recorded using a 0–10 visual analog scale (VAS). Peak mean swallowing problems were recorded using a 0–5 VAS. Days to absolute neutrophil count of more than 0.5 g/L and days to platelets of more than 20 g/L were recorded.
Interventions and complications were measured in terms of duration of analgesics used (days), duration of total parenteral nutrition (TPN) (days), use of granulocyte colony-stimulating factor (G-CSF), incidence of acute graft-versus-host disease (aGVHD), degree of aGVHD, and incidence of infectious complications.
The findings in this prospective randomized, controlled study confirm findings in a 1992 report of a double-blind, prospective, randomized, controlled trial of 95 patients undergoing HSCT. In that trial, SCPR produced statistically significantly lower measures of pain duration, disease course duration, use of analgesics (morphine), and duration of time to absolute neutrophil recovery than did a fluoride rinse, demonstrating the SCPR regimen has a significant positive effect on oral mucositis associated with chemotherapy and radiotherapy.
These results warrant confirmation in controlled, multicenter, randomized trials. The use of a supersaturated calcium phosphate rinse holds promise for the prevention and early resolution of oral mucositis and appears to have no significant side effects when used four times daily in patients receiving stem cell transplant.
Papas, A.S., Clark, R.E., Martuscelli, G., O’Loughlin, K.T., Johansen, E., & Miller, K.B. (2003). A prospective, randomized trial for the prevention of mucositis in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplantation, 31, 705–712.
Patients rinsed with 30 ml of calcium phosphate at least four times per day. Patients also received four topical treatments of 1% fluoride as neutral 2% sodium fluoride gel administered by tray at the screening visit and completed prior to hospitalization.
Patients in the control group received an aqueous 0.01% sodium fluoride rinse. Prior to transplantation, the control group received four topical treatments with a placebo gel administered with the same technique as the experimental group. During transplantation, patients used the sodium fluoride rinse at least four times daily, 30 ml each time.
Patients who developed severe mucositis were instructed to rinse up to 10 times per day with their solution.
All patients received acyclovir and antifungal prophylaxis per protocol.
This was a randomized, controlled trial.
The National Institute of Dental and Craniofacial Research scale was used.
The following were measured and recorded.
Pettit, L., Sanghera, P., Glaholm, J., & Hartley, A. (2014). The use of MuGard™, Caphosol® and Episil® in patients undergoing chemoradiotherapy for squamous cell carcinoma of the head and neck. Journal of Radiotherapy in Practice, 13(2), 218–225.
To record mucositis and dysphagia toxicity and level of anesthesia for patients receiving MuGard, Caphosol, or Episil in comparison to standard care
Patients undergoing concurrent radiotherapy and chemotherapy for locally advanced head and neck cancer were audited for eight weeks during treatment. Patients were sequentially given either the standard oral care regimen of aspirin, glycerin, and sucralfate and Gelclair® or one of the other products. Patients were assessed weekly during four weeks of radiotherapy and for four weeks after completion. All patients received the same protocol approach for analgesia.
PHASE OF CARE: Active antitumor treatment
Common Terminology Criteria for Adverse Events v3
No differences were seen between groups in average grade of dysphagia or analgesia use. No differences were seen between those receiving radiotherapy with intensity-modulated radiation therapy or conformal radiotherapy.
This study had numerous design limitations and provides little supportive evidence for any of the approaches used for prevention and management of oral mucositis or associated pain.
Raphael, M.F., den Boer, A.M., Kollen, W.J., Mekelenkamp, H., Abbink, F.C., Kaspers, G.J., . . . Tissing, W.J. (2014). Caphosol, a therapeutic option in case of cancer therapy-induced oral mucositis in children?: Results from a prospective multicenter double blind randomized controlled trial. Supportive Care in Cancer, 22, 3–6.
To evaluate if Caphosol™ is effective to treat oral mucositis (OM) in pediatric patients who received chemotherapy or hematopoietic stem cell transplant (HSCT)
A sample of 33 patients between 4–18 years old was assigned to Caphosol or placebo. All patients received standard local supportive care, in addition to Caphosol study or 0.9% sodium chloride (NaCl) placebo mouth rinse. All patients were instructed to use the study mouthwash four times daily during their OM period. Primary study outcome was defined as the number of days with OM greater than grade 1. Secondary outcomes were pain and analgesic use.
Chi-square or t-test was used for analysis. The number of days with mucositis greater than grade 1 did not differ significantly between the two study groups (p = 0.154). No significant differences were found between Caphosol and placebo for all the outcome measures except days of pain and tube feeding requirement. Placebo was associated with significantly fewer days of pain (p = 0.035) . The need for tube feeding was significantly higher in the Caphosol group.
Therapeutic use of Caphosol was not beneficial in the treatment of pediatric patients with cancer therapy-induced OM.
Although this study was a double-blind, randomized, controlled trial, the significantly small sample size was problematic. The authors concluded that Caphosol was not effective in practice; however, it is not conclusive because of the significantly high risk for type II errors. A study with a larger sample size is required to assess the efficacy of Caphosol.
Stokman, M. A., Burlage, F.R., & Spijkervet, F.K. (2012). The effect of a calcium phosphate mouth rinse on (chemo) radiation induced oral mucositis in head and neck cancer patients: A prospective study. International Journal of Dental Hygiene, 10(3), 175–180.
To determine the effect of a calcium phosphate (CP) mouth rinse on oral mucositis
Consecutive patients were asked if they were willing to use the CP mouth rinse. Those who were willing were assigned to the CP group, and those who refused served as controls and followed the standard oral care program. Standard care with mouth rinsing with a salt and baking soda solution at least 8 times per day. The CP rinse was used twice per day. All patients received daily oral cleansing with a normal saline pressure spray and fluoride gel applications every other day to the teeth. The study period was 6 weeks. Outcomes were compared between groups and compared with historical controls.
The study was conducted at a single outpatient site in the Netherlands.
Patients were undergoing the active antitumor treatment phase of care.
This was a prospective, non-random comparison study.
No significant differences were found between groups in any of the outcome measures. Patients in the CP group had more severe mucositis scores at most weeks, but the difference was not statistically significant.
CP mouth rinsing had no effect on frequency, severity, or duration of oral mucositis in this group of patients.
This study did not show any benefit in the use of CP mouth rinses for the prevention and management of mucositis in patients receiving radiation therapy for head and neck cancer.
Svanberg, A., Ohrn, K., & Birgegard, G. (2015). Caphosol mouthwash gives no additional protection against oral mucositis compared to cryotherapy alone in stem cell transplantation. A pilot study. European Journal of Oncology Nursing, 19, 50–53.
To determine whether the addition of Caphosol® mouth rinse to a standard of care that included oral cryotherapy would decrease the incidence of oral mucositis
Patients were randomized with a computer table to the experimental or the control group. All patients received oral cryotherapy (crushed ice in the mouth during treatment), but only the experimental group received Caphosol®. Patients in the experimental group used Caphosol® 30 mL to rinse the oral cavity four times per day starting before high-dose chemotherapy and ending on day 21. Data were collected daily from the start of chemotherapy till day 21.
Randomized, controlled, open-label study
There was no statistically significant difference between the mucositis scores, oral pain, days with TPN, use of opioids, number of hospital days, or lab values.
Adding Caphosol® to oral cryotherapy did not provide any additional effects.
Oral mucositis continues to be a major complication of chemotherapy, particularity high-dose chemotherapy. Additional research with larger sample sizes is suggested because of a trend of lower pain levels, mucositis scores, and use of analgesics in patients using Caphosol®. The 21-day use of Caphosol® and the discontinuation of Caphosol® because of taste or nausea are other items that merit additional study.
Treister, N., Nieder, M., Baggott, C., Olson, E., Chen, L., Dang, H., . . . Sung, L. (2016). Caphosol for prevention of oral mucositis in pediatric myeloablative haematopoietic cell transplantation. British Journal of Cancer, 116, 21–27.
To determine whether topically administered Caphosol, rinsed orally four times daily at the initiation of conditioning, reduces the duration of severe oral mucositis (OM) compared with placebo among children and adolescents undergoing hematopoietic cell transplantation (HCT)
Supplied Caphosol A (phosphate solution) and B (calcium solution) or sterile 0.9% sodium chloride solution were provided by two unblinded pharmacists after patients were randomized 1:1 between treatment and control groups. The nurses mixed the Caphosol in the syringes to form a pH-neutral supersaturated solution. The children and adolescents rinsed their mouths thoroughly for one minute, gargled, and spit with one-half of the mixed solution. They repeated with the remaining solution for a total rinse time of two minutes. Younger children with small mouths could rinse with a reduced volume. Participants rinsed four times per day (two rinses per episode) at approximately evenly spaced intervals. The therapy was initiated on the first day of conditioning and continued daily until after day 20 or hospital discharge, whichever occurred first. The subjects were assessed daily for OM by trained study staff until refusal by patient to participation, day +2-, or discharge home. Common Terminology Criteria for Adverse Events (CTCAE) criteria were used to assess toxicity.
Phase III, international, multicenter, randomized, double-blinded, placebo-controlled, prospective clinical trial. The primary endpoint was the duration of severe OM (World Health Organization [WHO] score of 3 or greater).
The mean duration of severe OM was not reduced among Caphosol (4.5, SD = 5 days) versus placebo (4.5, SD = 4.8; p = 0.99) recipients. No significant differences existed in any of the secondary endpoints between the groups.
Caphosol did not reduce severe OM compared with placebo among children and adolescents undergoing myeloablative HCT.
Caphosol did not reduce severe OM compared with placebo among children and adolescents undergoing myeloablative HCT. Effective interventions for OM is needed in this and in other populations.
Wong, K.H., Kuciejewska, A., Sharabiani, M.T., Ng-Cheng-Hin, B., Hoy, S., Hurley, T., . . . Newbold, K.L. (2016). A randomised controlled trial of Caphosol mouthwash in management of radiation-induced mucositis in head and neck cancer. Radiotherapy and Oncology, 122, 207–211.
To evaluate the efficacy of Caphosol mouthwash in the management of patients with head and neck cancer receiving (chemo)radiotherapy who have radiation-induced oral mucositis (OM)
Prior to receiving (chemo)radiotherapy, patients were randomized 1:1 to receive a standard oral care regimen (control) with or without Caphosol mouthwash. Those patients randomized to Caphosol used it from week 1–6 of radiation and then one week postradiation, at least four times per day, but could be increased up to 10 times per day per the patient or physician discretion. Other interventions for symptom control were allowed during the study. The patients randomized to the control arm received standard OM treatment per the institutions guidelines, which consisted of normal saline rinses at least four times per day, fluoride toothpaste with brushing, and aspirin mouthwash three times per day. Training on the use of Caphosol was provided by EUSA Pharma.
PHASE OF CARE: Active antitumor treatment
Phase III, single institution, non-blinded, randomized, controlled trial
Patients were assessed at baseline and prospectively every week for six weeks during radiation therapy and until four weeks postradiation therapy. Physicians trained on the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, performed the scoring of radiation-induced adverse events. Quality of life was assessed at baseline, week 4 of radiation therapy, week 4 of postradiation therapy, and week 8 of postradiation therapy using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Model (EORTC QLQ-C30), version 3.0, and the Quality of Life Questionnaire Head and Neck Module (QLQ-HN35).
In this large study, prophylactic Caphosol mouthwashes with standard OM treatment did not show a benefit versus standard OM treatment alone in reducing the incidence of OM or shortening the duration of OM in patients receiving (chemo)radiotherapy for head and neck cancer.
No evidence suggests that this intervention would benefit the type of patients studied. The cost of Caphosol would not be warranted, and its use could actually negatively affect patients because of the poor taste and potential for nausea.