The MASCC/ISOO Mucositis Guidelines: dissemination and clinical impact

This editorial introduces the second set of articles related to the update of the clinical practice guidelines for mucositis, developed by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO)

Nasal vestibulitis due to targeted therapies in cancer patients

BACKGROUND AND PURPOSE: Cancer patients treated with targeted therapies (e.g., epidermal growth factor receptor inhibitors) are susceptible to dermatologic adverse events (AEs) including secondary skin infections. Whereas infections such as paronychia and cellulitis have been reported, nasal vestibulitis (NV) has not been described with the use of these agents. The aim of our study was to characterize NV in cancer patients treated with targeted therapies. METHODS: We utilized a retrospective chart review of cancer patients who had been referred to dermatology and were diagnosed with NV. We recorded data including demographics, referral reason, underlying malignancy, targeted anticancer regimen, NV treatment, and nasal bacterial culture results. RESULTS: One Hundred Fifteen patients were included in the analysis, of which 13 % experienced multiple NV episodes. Skin rash was the most common reason (90 %) for a dermatology referral. The most common underlying malignancies were lung (43 %), breast (19 %), and colorectal (10 %) cancer. Sixty-eight percent of patients had been treated with an EGFRI-based regimen. Nasal cultures were obtained in 60 % of episodes, of which 94 % were positive for one or more organisms. Staphylococcus aureus was the most commonly isolated organism [methicillin-sensitive S. aureus 43 %; methicillin-resistant S. aureus 3 %]. CONCLUSIONS: We report the incidence and characteristics of an unreported, yet frequent dermatologic condition in cancer patients treated with targeted therapies. These findings provide the basis for additional studies to describe the incidence, treatment, and consequences of this event. A better understanding of NV would mitigate its impact on patients’ quality of life and risk for additional dermatologic AEs

Phase i and pharmacological study of pazopanib in combination with oral topotecan in patients with advanced solid tumours

Background: This phase I study evaluated the safety, tolerability, maximum tolerated dose (MTD) and pharmacokinetics of two dosing schedules of oral topotecan in combination with pazopanib in patients with advanced solid tumours. Methods: Stage I of this study was to determine whether there was an impact of pazopanib on topotecan exposure. In stage II, the MTD and safety profile of oral topotecan given weekly on days 1, 8 and 15 in a 28-day cycle; or daily-times-five on days 1-5 in a 21-day cycle, both in combination with daily pazopanib, were explored. Results: In total, 67 patients were enroled. Pazopanib co-administration caused a substantial increase in exposure to total topotecan (1.7-fold) compared with topotecan alone, which is considered clinically relevant. Topotecan had no effect on pazopanib concentrations. Safety findings were consistent with the known profile of both agents. There were three drug-related deaths, liver failure, tumour haemorrhage and myelosuppression. Two patients experienced dose-limiting toxicities (DLTs; hand-foot syndrome, myelosuppression and diarrhoea) on the weekly topotecan schedule and four patients experienced DLTs (myelosuppression) on the daily-times-five topotecan schedule. When combined with pazopanib, 800 mg daily, the recommended doses for oral topotecan are: 8 mg weekly and 2.5 mg daily-times-five. Seven of eight patients with partial response had platinum-resistant ovarian cancer. In addition, 54% of patients had stable disease with 22% stable for 6 months. Conclusions: Total topotecan exposure is 1.7-fold higher when co-administered with pazopanib. Both schedules of administration were tolerated and would permit further evaluation, especially the weekly schedule

Cognitive interviewing of the US National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

PURPOSE: The National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a library of question items that enables patient reporting of adverse events (AEs) in clinical trials. This study contributes content validity evidence of the PRO-CTCAE by incorporating cancer patient input of the relevance and comprehensiveness of the item library. METHODS: Cognitive interviews were conducted among patients undergoing chemotherapy or radiation therapy at multiple sites to evaluate comprehension, memory retrieval, judgment, and response mapping related to AE terms (e.g., nausea); attribute terms (regarding frequency, severity, or interference); response options; and recall period. Three interview rounds were conducted with ≥20 patients completing each item per round. Items were modified and retested if ≥3 patients exhibited cognitive difficulties or if experienced by ≤25% patients. RESULTS: 127 patients participated (35% ≤high school; 28% non-white; 59% female). Most AE terms (63/80) generated no cognitive difficulties. The remaining 17 were modified without further difficulties by Round 3. Terms were comprehended regardless of education level. Attribute terms and response options required no modifications. Patient adherence to recall period (7-days) was improved when the reference period was incorporated. CONCLUSIONS: This study provides evidence confirming comprehension of the U.S. English language versions of items in the PRO-CTCAE library for measuring symptomatic AEs from the patient perspective within the context of cancer treatment. Several minor changes were made to the items to improve item clarity, comprehension, and ease of response judgment. This study helps establish the content validity of PRO-CTCAE items for patient reporting of AEs during cancer treatment