Purpose: Sodium stibogluconate (SSG), a small molecule inhibitor of protein tyrosine phosphatases, combined with IFN-alpha-2b (IFN-α) inhibited solid tumor cell line growth in vitro. We conducted a phase I clinical trial with SSG plus IFN-α in advanced cancer patients to assess tolerance, maximum tolerated dose (MTD) and immune system effects.Experimental Design: SSG was administered intravenously alone for five days of week 1, cycle 1 (21 days per cycle) and together with IFN-α 2b s (3 million units sc TIW) in week 2, and after a rest during week 3, on a 2-week on/1-week off cycle. SSG dose levels were 400, 600, 900, 1125, and 1350 mg/m2.Results: Twenty-four patients were studied. Common toxicities included asymptomatic elevated serum lipase, thrombocytopenia, fatigue, fever, chills and anemia. The dose-limiting toxicities (DLT) were hypokalemia, thrombocytopenia, fatigue, pancreatitis and skin rash. The MTD was 900 mg/m2 SSG and IFN-α, 3 million units TIW. At this dose, patients had a significantly lower number of regulatory T cells (TR Cells) (p = 0.012), myeloid dendritic cells (mDC) (p = 0.028); higher percentage of natural killer (NK) cells that synthesized perforin (p = 0.046) and of plasmacytoid dendritic cells (pDC) that secreted IFN-α (p = 0.018) in response to activation through toll-like receptor (TLR) 7 and TLR 8 by CL097, the highly water-soluble derivative of the imidazoquinoline compound R848.Conclusions: SSG in combination with IFN-α 2b was well tolerated and augmented cellular immune parameters.
Our study found that 1 mg of IV hydromorphone is equivalent to 2.5 mg of oral hydromorphone and 11.46 mg of MEDD. Hydromorphone at doses ≥30 mg/day may require a lower ORR to other opioids.
Background: A question prompt sheet (QPS) is a structured list of potential questions available for patients to ask their doctor during a clinical encounter. Although it has been shown to improve physician-patient interaction during clinical consultations, there is paucity of data on its use in the palliative care setting. The aim of this study was to develop a single-page consensus list of prompt questions for use by patients attending outpatient palliative care. Method: An expert group of experienced physicians and mid-level providers were invited to participate in the study conducted in three Delphi rounds. A consensus in this study was defined a priori as an agreement (i.e., agree or strongly agree) by a minimum of 80% of the experts. Results: One hundred percent of the 22 invited experts participated in all the three Delphi rounds of the study. The top 25 questions with the highest level of endorsement were chosen and used toward the development of the QPS. Twenty-eight percent of the questions were about symptoms, treatment, and lifestyle, 24% were about commonly asked questions by caregivers, 20% were regarding end-of-life issues, 16% were regarding the nature of the palliative care service, and 12% were regarding the type of available support. Conclusion: A 25-item, single-page QPS was developed for use by patients attending outpatient palliative care. Further studies are needed to determine its clinical effectiveness in assisting physician-patient communication.
197 Background: Inpatients with cancer frequently undergo conversions from IV to PO hydromorphone (HM) or opioid rotation (OR) from IV HM to another PO opioid prior to discharge. Currently used conversion ratios (CR) between IV and PO HM range from 2-5 and opioid rotation ratios (ORR) between IV HM and oral morphine equivalent daily dose (MEDD) range from 10-20. This large variation in ratios may lead to uncontrolled pain or overdosing. Our aim was to determine the accurate CR from IV to PO HM and ORR from IV HM to PO morphine and oxycodone (measured as MEDD). Methods: We reviewed records of 4745 consecutive inpatient palliative care consults in our institute during 2010-14 for patients who underwent conversion from IV to PO HM or OR from IV HM to PO morphine or oxycodone. Patient characteristics, symptoms and opioid doses were determined in patients successfully discharged on oral opioids without readmission within 1 week. Linear regression analysis was used to estimate the CR or ORR between the 24 hour IV HM mg dose prior to conversion to PO and the oral opioid mg dose used in the 24 hours prior to discharge. Results: Among 394 eligible patients on IV HM, 147 underwent conversion to PO HM and 247 underwent OR to oral morphine (163) or oxycodone (84). Mean age was 54 years, 39% were male, and 95% had advanced cancer. Median time between conversion to PO and discharge was 2 days. In 147 patients the median CR (IQR) from IV to PO HM was 2.5 (2.1-2.7) and correlation of IV to PO dose of HM was .95 (P < .0001). The median CR was 2.5 in patients receiving < 30mg of IV HM/day and 2.1 in patients receiving ≥ 30mg of HM/day (P = .004). In 247 patients the median ORR (IQR) from IV HM to MEDD was 11.5 (10-13) and correlation of IV HM to MEDD was .93 (P < .0001). The median ORR was 11.5 in patients receiving < 30mg of IV HM/day and 9.9 in patients receiving ≥ 30mg of HM/day (P = .0004). ORR from IV HM to MEDDs obtained from morphine (11) and oxycodone (12.1) were significantly different (P = .0023). The CR and ORR were not significantly impacted by other variables. Conclusions: The median CR from IV to PO HM is 2.5 and ORR from IV HM to MEDD is 11.5. This implies that 1 mg IV HM is equivalent to 2.5 mg PO HM and 11.5 mg MEDD. HM may cause hyperalgesia at doses ≥ 30 mg/day and thereby requires a lower ORR to other opioids.
Our findings suggest that significant simplification and intensive education is necessary for successful adoption of a scoring system. More research is needed in order to identify how to adopt tools for daily clinical practice in palliative care.
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