Morphine bioavailability from a topical gel formulation in volunteers

Although available therapies provide relief to many patients with cancer-related pain, swallowing difficulties or intestinal obstruction may preclude oral analgesic delivery in some. Topical morphine might provide an alternate delivery form but morphine bioavailability from a topical gel formulation has not been reported in humans. We conducted a randomized, placebo-controlled, double-blind, crossover study of five volunteers after they provided institutionally-approved, written, informed consent. They were admitted to the Northwestern University General Clinical Research Center twice, being randomly assigned to receive either 1mL of morphine compounded at 10mg/mL in pluronic lecithin organogel (PLO) base applied to the wrist and 1mL of normal saline administered subcutaneously, or 1mL of topical drug-free PLO base and 1mL of subcutaneous morphine, 3mg/mL, the first time and the opposite combination the second. Seventeen blood samples were collected from 5minutes to 10hours after dose administration for morphine concentration determination. Plasma samples were prepared by solid-phase extraction and morphine concentrations measured by a mass spectrometric technique with a linear range of 0.5-500ng/mL. Bioavailability of the topical formulation relative to the subcutaneous dose was to be estimated from doses and the plasma morphine concentration versus time relationships. Because morphine was seldom detected in plasma samples after topical administration and was unquantifiable when it was, the low bioavailability of topical morphine was unquantifiable. These results suggest that topical administration of morphine compounded in a PLO base for transdermal drug delivery is unlikely to provide relief of cancer-related pain.     

How Well Do Medical Oncologists Manage Chronic Cancer Pain? A National Survey

Background.

Cancer pain is usually managed by oncologists, occasionally with input from specialists in hospice and palliative medicine (PLM) or pain medicine (PMD). We evaluated the knowledge of cancer pain management in these three specialty groups.

Methods.

Eight vignettes depicting challenging scenarios of patients with poorly controlled pain were developed; each had five or six treatment choices. Respondents indicated choices likely to be safe and efficacious as “true” and choices likely to be unsafe or inefficacious as “false.” Two questionnaires were created, each with four vignettes. Three anonymous mailings targeted geographically representative U.S. samples of 570 oncologists, 266 PMD specialists, and 280 PLM specialists, each randomly assigned one version of the questionnaire. Vignette scores were normalized to a 0–100 numeric rating scale (NRS); a score of 50 indicates that the number of correct choices equals the number of incorrect choices (consistent with guessing).

Results.

Overall response rate was 49% (oncologists, 39%; PMD specialists, 48%; and PLM specialists, 70%). Average vignette score ranges were 53.2–66.5, 45.6–65.6, and 50.8–72.0 for oncologists, PMD specialists, and PLM specialists, respectively. Oncologists scored lower than PLM specialists on both questionnaires and lower than PMD specialists on one. On a 0–10 NRS, oncologists rated their ability to manage pain highly (median 7, with an interquartile range [IQR] of 5–8). Lower ratings were assigned to pain-related training in medical school (median 3, with an IQR of 2–5) and residency/fellowship (median 5, with an IQR of 4–7). Oncologists older than 46–47 years rated their training lower than younger oncologists.

Conclusion.

These data suggest that oncologists and other medical specialists who manage cancer pain have knowledge deficiencies in cancer pain management. These gaps help clarify the need for pain management education.     

Symptom management in the older adult

Palliative care begins at the time of diagnosis of a life-threatening illness and continues beyond the time of death. Defined in the broadest sense, the goal of palliative care is to provide aggressive symptom management and address the psychological and spiritual needs of the patient and the family. This article reviews the management of some symptoms commonly observed in older patients, highlighting treatment considerations specific to the older population. Ultimately the approach to symptoms must be individualized, and treatment decisions must reflect the patient's goals of care. Although symptom management in older patients may be challenging, it is possible to provide care that significantly enhances quality of life throughout the course of illness.     

Clinical aspects of human immunodeficiency virus-related lymphoma.

As patients with human immunodeficiency virus infection live longer because of better antiretroviral therapy and infection prophylaxis, the incidence of non-Hodgkin's lymphoma has increased. The risk increases inversely with CD4 count--the most widely used surrogate marker for progressive immune suppression. Zidovudine itself does not appear to be a risk factor. Patients frequently present with extranodal advanced disease. The central nervous system is the primary site in 10% to 20% of cases. Important prognostic factors are performance status, a prior history of acquired immunodeficiency syndrome, and bone marrow involvement. Therapy is complicated by underlying immunosuppression, opportunistic infection, and poor bone marrow reserve. Progress has been made using colony-stimulating factors and less intensive chemotherapy regimens in systemic non-Hodgkin's lymphoma. Treatment of primary central nervous system lymphoma with radiation therapy has not improved survival.     

Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus‐associated Kaposi sarcoma

BACKGROUND:

Paclitaxel and pegylated liposomal doxorubicin (PLD) are active cytotoxic agents for the treatment of human immunodeficiency virus (HIV)‐associated Kaposi sarcoma (KS). A randomized trial comparing the efficacy and toxicity of paclitaxel and PLD was performed, and the effects of therapy on symptom palliation and quality of life were determined.

METHODS:

Patients with advanced HIV‐associated KS were randomly assigned to receive paclitaxel at a dose of 100 mg/m² intravenously (iv) every 2 weeks or PLD at a dose of 20 mg/m² iv every 3 weeks. The KS Functional Assessment of HIV (FAHI) quality of life instrument was used before and after every other treatment cycle.

RESULTS:

The study included 73 analyzable patients enrolled between 1998 and 2002, including 36 in the paclitaxel arm and 37 in the PLD arm; 73% of patients received highly active antiretroviral therapy (HAART) and 32% had an undetectable viral load (<400 copies/mL). Treatment was associated with significant improvements in pain (P = .024) and swelling (P < .001). Of the 36 patients who reported that pain interfered with their normal work or activities at baseline, 25 (69%) improved. Of the 41 patients who reported swelling at baseline, 38 (93%) improved. Comparing the paclitaxel and PLD arms revealed comparable response rates (56% vs 46%; P = .49), median progression‐free survival (17.5 months vs 12.2 months; P = .66), and 2‐year survival rates (79% vs 78%; P = .75), but somewhat more grade 3 to 5 toxicity for paclitaxel (84% vs 66%; P = .077).

CONCLUSIONS:

Treatment with either paclitaxel or PLD appears to produce significant improvements in pain and swelling in patients with advanced, symptomatic, HIV‐associated KS treated in the HAART era. Cancer 2010. © 2010 American Cancer Society.     

A phase II study of single agent bortezomib in patients with metastatic breast cancer: a single institution experience

PS-341, now known as bortezomib (Velcade[Millenium Pharmaceuticals, Inc., Cambridge, MA; and Johnson & Johnson Pharmaceutical Research & Development, LLC, Spring house, PA]), is a proteasome inhibitor approved for the treatment of refractory multiple myeloma. Preclinical and early clinical studies showed PS-341 to be effective in solid tumors, one of which was breast cancer. We conducted a single institution, phase II study using PS-341 in the treatment of patients with metastatic breast cancer. The primary objective of this study was to determine the objective tumor response in patients with metastatic breast cancer (MBC) receiving PS-341. The secondary objectives were to estimate progression-free survival of patients receiving single-agent PS-341 and to evaluate toxicity related to PS-341. In all 12 patients who met criteria for enrollment, there were no observed objective responses. Further, all 12 patients progressed while receiving therapy with PS-341. This study was terminated after the first stage due to the lack of any objective response.     

A study of oncology fellows' training in end-of-life care

Caring for the dying is a core competency for oncologists, yet the quality of oncology fellowship training in end-of-life (EOL) care has not been assessed. A convenience sample of physicians attending the 2004 annual meeting of the American Society of Clinical Oncology responded to a 112-item questionnaire that assessed fellows' knowledge and education about EOL care. Of the 120 respondents, 107 (89%) rated caring for dying patients as"quite" or "very important. "Forty-two percent of the fellows rated the overall quality of teaching EOL care in their fellowship as "very good" or "excellent," whereas 23% gave such ratings to EOL teaching in fellowship (P < or = 0.001). Fellows viewed attending oncologists as having more expertise in dealing with acute complications of cancer (eg, managing spinal cord compression, 78%) than in delivering EOL care (eg, managing pain, 54%; P < 0.001). Fellows also were more likely to have received observation and feedback on bone marrow biopsies than on EOL discussions. Knowledge about key EOL care topics was poor; only 31% correctly performed an opioid conversion. Oncology fellows described deficiencies in training on EOL issues;they may benefit from improved education on EOL topics.     

Pilot neoadjuvant trial in HER2 positive breast cancer with combination of nab-paclitaxel and lapatinib

Lapatinib, a dual kinase inhibitor against epidermal growth factor receptor (EGFR) and human epidermal receptor two (HER2) has shown efficacy in treating HER2 positive breast cancer. Nanoparticle albumin bound (nab) paclitaxel was developed to reduce toxicities from paclitaxel and improve its efficacy. Thirty patients with stage I?CIII HER2 positive breast cancer were treated in the neoadjuvant setting with lapatinib 1,000?mg/day and nab-paclitaxel 260?mg/m² every 3?weeks for four cycles. The primary end point of the trial was clinical response rate (cRR) with secondary end points including pathologic complete response rate (pCR), tolerability of the combination, and marker response. The cRR was 82.8% (24 patients) with six (20.7%) patients having complete clinical response, 18 (62.1%) having partial clinical response, and five (17.2%) stable disease. A pCR was observed in five of the 28 patients (17.9%). The most frequent grade 2 toxicities were neuropathy in nine patients (30%), fatigue in seven patients (23.3%), rash in 11 patients (36.7%), and bone pain in 10 patients (33.3%). There was no significant drop in the left ventricular ejection fraction (LVEF). Of the tissue markers examined, we were not able to find a predictor of response. The combination of lapatinib and nab-paclitaxel was well tolerated and provided good efficacy in women with HER2 positive breast cancer. This combination offers an alternative non-anthracycline-containing regimen for women with HER2 positive breast cancer.