Caphosol in Oral Mucositis Due to Targeted Therapy

Targeted therapies such as multi-targeted tyrosine kinase inhibitors (TKI) and mammalian target of rapamycin inhibitors (mTORI) in renal cell carcinoma (RCC), demonstrate a high level of efficacy with acceptable tolerability. Currently, there are five approved targeted therapies available for RCC: sunitinib (Sutent®), sorafenib (Nexavar®), pazopanib (Votrient®), temsirolimus (Torisel®), and everolimus (Afinitor®). Hepatocellular carcinoma treated with sorafenib and gastro intestinal stromal tumors patients treated with sunitinib will be included, too. Since this agents have dermatological adverse events in common, with oral mucositis (OM), hand-foot skin reaction (HFSR) and papulopustular eruption (PPE) as an disabling side effect, we require evidence based management options to prevent and treat these adverse events. The incidence of OM of any grade is for sunitinib 38%, sorafenib 28%, pazopanib 4%, temsirolimus 41%, and everolimus 44%. Recent data suggest that TKI and mTORI associated OM is distinct from conventional mucositis and more closely resembles aphthous OM. Recently, supersaturated calcium-phosphate rinse (Caphosol®), a Ca2+/PO43- mouth rinse, became available to prevent or treat OM. The objective is to assess the relieving effect of Caphosol® oral rinse on clinical outcomes which include oral intake, swallowing function and pain associated with incidence of grade ≥ 1 oral side effects and the anticancer therapy cessation in patients treated with selected targeted anticancer therapy. Patients with OM \> grade 0 on targeted therapy will be randomly allocated to receive either Caphosol® or NaCl 0.9% rinse for two weeks. After the first rinse period all patients will switch to the opposite treatment arm (NaCl 0.9% or Caphosol®) for another two weeks. Duration of oral side effects, severity, pain, dose of analgesics and tolerability will be assessed weekly with the Modified-VHNSS-version-2.0 oral-specific questionnaire. Patients will be stratified by targeted anticancer agent and per tumor type (pre-defined cohorts). Objective severity of oral side effects will be assessed using the NCI-CTCAE v4.0. Correlation of subjective Modified-VHNSS-version-2.0 scores with the objective NCI-CTCAE grade, sex, age, targeted therapy type, and cancer type will be conducted.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Male and female subjects
* ≥18 years of age
* Histological proof of RCC, HCC or GIST
* Oral adverse events \> grade 0 due to sunitinib, sorafenib, pazopanib, temsirolimus, or everolimus in mono therapy at study entry
* Written informed consent
* Eastern Co-operative Oncology Group (ECOG) performance status ≤ 2
* Able to perform oral rinsing
* Able to complete questionnaires by themselves or with assistance

Exclusion Criteria:

* Any previous systemic antineoplastic treatment within 4 weeks of initiation of current targeted anticancer therapy
* Current antineoplastic combination cytotoxic chemotherapy therapy
* Physiologic condition that precludes the use of an oral rinse
* Hypersensitivity to Caphosol ingredients
* Use of palifermin, oral cryotherapy, low level laser therapy, topical oral steroids within 3 weeks of current targeted anticancer therapy
* Oral abnormalities defined as baseline oral assessment of NCI-CTCAE v4.0 grade \> 0
* Current use of agents that are known to be strong inducers or inhibitors of CYP3A4 that can not be stopped