Cutaneous squamous cell carcinoma in two pediatric lung transplant patients on prolonged voriconazole treatment

Oral voriconazole is commonly used for treatment and prophylaxis of invasive fungal disease post‐LTx. Development of cutaneous SCC has been described in adult LTx recipients, although it is extremely rare in children. We describe two Caucasian children who developed cutaneous SCC beyond three yr post‐LTx. Both developed severe photosensitivity, actinic keratosis and required curative surgical excision of the cutaneous SCC lesions. Neither patient developed metastatic lesions nor had allograft dysfunction as a result of the SCC or the change in medical treatments. The effect of voriconazole on the development of malignant skin lesions is discussed and a recommendation on dermatologic surveillance, preventive measures against phototoxicity and early treatment of SCC are provided.     

Phase I trial of oral estramustine and 3-hr infusional paclitaxel for the treatment of hormone refractory prostate cancer

PRECIS: Estramustine 600 mg/m2 can be administered safely with 225 mg/m2 of paclitaxel if administered as a 3-hr infusion for the treatment of hormone refractory prostate cancer. Significant anti-tumor activity has been reconfirmed despite the change in schedule of administration of the paclitaxel. PURPOSE: This phase I study was conducted to identify the maximum tolerated dosage of paclitaxel administered as a 3-hr infusion combined with a stable dosage of estramustine capsules daily in men with hormone refractory prostate cancer. A secondary endpoint was to assess anti-tumor efficacy in this targeted patient population. PATIENTS AND METHODS: Twenty-six male patients, all with hormone refractory prostate cancer were enrolled in this trial. Estramustine was administered at a dosage of 600 mg/m2 daily, and paclitaxel was dose-escalated in cohorts from 125 to 250 mg/m2 administered as an infusion over 3 hr every 21 days. Patients were treated until maximum response was achieved, or toxicity or progressive disease precluded further treatment. Toxicity to determine maximum tolerated dose was assessed only during the first 3-week cycle. RESULTS: The maximum tolerated dose of paclitaxel on this schedule was 225 mg/m2 based on unacceptable dose-limiting fatigue observed at the next higher dosage level. Other grade 3 or 4 events included myelosuppression, left ventricular dysfunction, elevated liver function tests, deep venous thrombosis, vomiting, and development of depression. Using a response criteria of prostate specific antigen decline of > 50% persisting for a minimum of 6 weeks, eight of 26 patients responded (30.8%). Two of seven patients with documented soft-tissue disease experienced > 50% reductions in size of lesions or number of sites. The median response duration was 6 months, and the median survival time was 16 months. CONCLUSION: The recommended phase II dose of paclitaxel is 225 mg/m2 when administered over 3 hr in combination with estramustine. This regimen has an acceptable toxicity profile, is a convenient schedule, and results in significant antitumor activity even in a heavily pre-treated population of patients.     

Cutaneous T-cell lymphoma: a paradigm for biological therapies

Mycosis Fungoides and Sézary Syndrome are the most common types of cutaneous T-cell lymphomas. There is no current standard of care for Mycosis Fungoides/Sézary Syndrome, with a general tendency to rely on topical interventions for early disease delaying systemic, more toxic therapy until the development of extensive symptoms. Knowledge of the biological characteristics of this disease has allowed for the development of rational interventions and a significant advance in its treatment. Retinoids are active in Mycosis Fungoides/Sézary Syndrome with the newer rexinoids being available in topical and systemic forms. Interferon alpha remains one of the most active therapeutic agents for Mycosis Fungoides/Sézary Syndrome, especially in combination with other agents such as PUVA. The monoclonal antibody alemtuzumab leads to responses in at least half of patients with advanced disease with its side effect profile consisting mainly of immunosupression and infusion reactions. The recombinant IL2-diphteria toxin denileukin diftitox (Ontak) is active in this disease and appears to have a beneficial effect in symptoms relief and quality of life. Extracorporeal photochemotherapy as an immunostimulating intervention seems to be very effective in a subset of patients, but its availability is limited to less than a hundred centers worldwide. Experimental and less studied interventions include autologous and allogeneic peripheral stem cell transplantation, Interleukin-12, the histone-deacetylator depsipeptide and the synthetic deoxynucleotide CpG7909. Cutaneous T-cell lymphoma has served as a paradigm for the development of biological agents. Further knowledge of the signaling pathways in Mycosis Fungoides/Sézary Syndrome will allow for the development of more effective treatment strategies.     

High-dose therapy and bone marrow transplantation in cutaneous T-cell lymphoma

Although most patients who have cutaneous T-cell lymphoma have an indolent clinical course, patients who have cutaneous tumors, lymph node or visceral involvement, or peripheral blood involvement generally have rapidly progressive disease with shorter survival. In those patients with poor prognostic features, conventional combination chemotherapy is usually ineffective. High-dose chemotherapy with autologous hematopoietic stem cell transplant (HSCT) results in high remission rates, but the recurrence is inevitable and rapid. Allogeneic HSCT, in contrast, provides durable long-term remissions and is currently the only potentially curative therapy.     

Making the case for a qualitative study of medical errors in primary care

In the interest of publicizing examples of funded qualitative health research, the authors share a proposal to the Agency for Healthcare Research and Quality in Washington, D.C., in which they sought to elicit patient stories of preventable problems in their primary health care that were associated with psychological or physical harms. These stories would allow for the construction of a tentative typology of errors and harms as experienced by patients and the contrasting of this with errors and harms reported by primary care physicians in the United States and other countries. The authors make explicit the anticipated concerns of reviewers more accustomed to quantitative research proposals and the arguments and strategies employed to address them.