A Phase 1 study Combining Pexidartinib, Radiation Therapy, and Androgen Deprivation Therapy in Men With Intermediate- and High-Risk Prostate Cancer.

PURPOSE: This study aimed to evaluate a combination of radiation therapy (RT), androgen deprivation therapy (ADT), and pexidartinib (colony-stimulating factor 1 receptor [CSF1R]) inhibitor in men with intermediate- and high-risk prostate cancer. CSF1R signaling promotes tumor infiltration and survival of tumor-associated macrophages, which in turn promote progression and resistance. Counteracting protumorigenic actions of tumor-associated macrophages via CSF1R inhibition may enhance therapeutic efficacy of RT and ADT for prostate cancer. METHODS AND MATERIALS: In this phase 1 study, the treatment regimen consisted of pexidartinib (800 mg, administered as a split-dose twice daily) and ADT (both for a total of 6 months), and RT that was initiated at the start of month 3. RT volumes included the prostate and proximal seminal vesicles. The delivered dose was 7920 cGy (180 cGy per fraction) using intensity modulated RT with daily image guidance for prostate localization. The primary objective was to identify the maximum tolerated dose based on dose-limiting toxicities. RESULTS: All 4 enrolled patients who were eligible to receive RT had T1 stage prostate cancer, 2 were intermediate risk, and 2 were high risk. The median age was 62.5 years, and the prostate-specific antigen levels were in the range 6.4 to 10.7 ng/mL. The patients' individual Gleason scores were 3 + 3, 4 + 3, 4 + 4, and 4 + 5. All 4 patients reported ≥1 adverse events before RT. Grade 1 hypopigmentation was observed in 1 patient, and grade 3 pulmonary embolus in another. One patient experienced fatigue and joint pain, and another elevated amylase and pruritus (all grade 3 toxicities). Five of the 6 adverse events noted in 3 patients were all grade 3 toxicities attributable to pexidartinib, qualifying as dose-limiting toxicities and ultimately resulting in the study closure. CONCLUSIONS: The combination was not well tolerated and does not warrant further investigation in men with intermediate- and high-risk prostate cancer.

Management of severe neuropathic cancer pain: an illustrative case and review.

Neuropathic cancer pain is common, very disabling and difficult to treat. It can be related to tumor invasion of neural structures and neuronal damage by surgery, chemotherapy and radiation therapy. Adjuvant analgesics are often used with opioids to control neuropathic pain in cancer patients. Methadone, a synthetic opioid with multiple mechanisms of action, is gaining increasing importance as an effective agent in the treatment of cancer related neuropathic pain. This case illustrates the challenges of managing severe pain in a patient with head and neck cancer while undergoing anti-tumor treatment. A review of the adjuvant analgesics and opioids, particularly methadone, in the management of neuropathic pain is also included.

Prioritization of the National Dental Hygiene Research Agenda.

The profession of dental hygiene has made considerable progress over the past 30 years toward developing a unique body of knowledge for guiding education, practice, and research. The 1993-1994 American Dental Hygienists' Association Council on Research published the first national dental hygiene research agenda in 1994. The 1994 research agenda focused dental hygienists' research efforts; however, publication of two national reports--the Surgeon General's Report on Oral Health, and Healthy People 2010--have made it necessary to revisit the research agenda. After considering input from participants in the Fourth National Dental Hygiene Research Conference and evaluating the Surgeon General's Report, the 2000-2001 Council on Research has established recommendations for the prioritization of the 1993-1994 research agenda. This report outlines for readers the rationale for the proposed recommendations.