Plasma and saliva levels of three metals in waterpipe smokers: a case control study.

In this case-control study, the influence of waterpipe tobacco smoking on the plasma and saliva levels of cadmium, lead and zinc was examined in participants who were waterpipe tobacco smokers (WS) or never-smokers (NS). The concentration of metals was higher in WS relative to NS. The mean (SEM) cadmium concentration in plasma was 3.3 (0.18) µg/dL in WS versus 0.82 (0.09) µg/L in NS (p < .001) and in saliva was 5.1 (0.36) µg/L in WS versus 0.64 (0.2) µg/L in NS (p < .001). The mean (SEM) lead concentration in plasma was 5.2 (0.25) µg/dL in WS versus 3.4 (0.41) µg/dL in NS (p < .01) and in saliva was 4.8 (0.58) µg/L in WS versus 2.8 (0.27) µg/L in NS (p < .05). Similarly, a significant difference in zinc concentration was observed, with a mean of 2.0 (0.17) µg/mL in WS plasma versus 1.49 (0.16) µg/mL in NS (p < .05) and a mean 0.94 (0.07) µg/mL in WS saliva versus 0.45 (0.06) µg/mL in NS (p < .01). In conclusion, waterpipe tobacco smoking is associated with elevated levels of metals in body fluids. These results provide another demonstration of how waterpipe tobacco smoking exposes smokers to harmful toxicants.

Smoking-cessation practice guidelines: awareness and implementation among medical teams.

OBJECTIVES: The aim was to evaluate the awareness and implementation of the Smoking Cessation Clinical Practice (SCCP) guidelines. METHODS: A self-reported questionnaire based on the updated version of the SCCP guidelines was completed by 422 healthcare providers (HCPs) including physicians, dentists, dental hygienists and pharmacists recruited from both public and private sectors in Jordan. KEY FINDINGS: The majority of HCPs reported good smoking-cessation practices. However, their awareness about the SCCP guidelines was inadequate. Approximately 68% of HCPs lacked knowledge of the 5As; about 74% lacked knowledge of the 5Rs of the clinical guidelines for smoking cessation, which are the principal guidelines for smoking intervention and motivation to quit smoking. Fortunately, about 70% of participants from all groups examined and applied most of the steps in the guideline spontaneously without previous knowledge of the guideline. This spontaneous practice could be due to their vast practical experience, and the use of logic and/or basic knowledge about smoking cessation. Compared to physicians, pharmacists and dental hygienists showed significantly more frequent practice of most steps with patients willing to quit smoking. CONCLUSIONS: Jordanian HCPs showed good, spontaneous smoking-cessation practice. However, this practice could have been better if HCPs had adequate awareness of the SCCP guidelines.

A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.

PURPOSE: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer. PATIENTS AND METHODS: Patients received either G+C (guadecitabine 30 mg/m2 s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS). RESULTS: Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group. CONCLUSIONS: Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.

Phase 1B study of amuvatinib in combination with five standard cancer therapies in adults with advanced solid tumors.

PURPOSE: Amuvatinib is an oral multi-kinase inhibitor that suppresses RAD51, inhibits mutant c-KIT and platelet-derived growth factor receptor alpha, and has synergistic activity with DNA-damaging agents and topoisomerase inhibitors such as etoposide, doxorubicin, and topotecan. We conducted a phase 1B study to estimate the maximum tolerated dose (MTD) levels of amuvatinib with standard chemotherapy regimens and to define the safety profiles of specific amuvatinib + standard regimens. METHODS: Five therapies each co-administered with amuvatinib 100-800 mg/day every 21 days were evaluated in treatment-naïve or moderately pre-treated subjects: paclitaxel IV followed by carboplatin IV; carboplatin IV followed by etoposide; topotecan IV; docetaxel IV; and erlotinib by mouth. RESULTS: Among 97 treated subjects, no treatment arm reached the MTD. Dose-limiting toxicities included febrile neutropenia and diarrhea. No pharmacokinetic interactions of amuvatinib with any cancer regimens occurred. Of 12/97 (12 %) partial responses overall, 11 were seen in the amuvatinib and paclitaxel/carboplatin or carboplatin/etoposide arms and most commonly in the neuroendocrine (NE), non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC) tumors. Forty-four subjects (45 %) had stable disease. Adverse events reflected combination treatment and were primarily non-hematologic (fatigue, alopecia, diarrhea, nausea, anorexia) and hematologic (neutropenia, anemia, thrombocytopenia, leukopenia). Pharmacodynamic effects as measured by decreased levels of RAD51 and increased residual DNA damage (53BP1 foci) were seen in skin punch biopsies. CONCLUSION: Amuvatinib was well tolerated, modulated RAD51, and showed antitumor activity when combined with paclitaxel/carboplatin and carboplatin/etoposide in NE, NSCLC, and SCLC tumors.