The development of biologic end points in patients treated with differentiation agents: an experience of retinoids in prostate cancer.
The evaluation of new therapies in prostate cancer requires unique end points for agents with diverse mechanisms of action. Because retinoic acid may have a confounding effect on prostate-specific antigen, we incorporated a pathological end point into the outcome assessment of two sequential clinical trials using all-trans-retinoic acid (ATRA) and the combination of 13-cis-retinoic acid and IFN-2a (cRA inverted question markIFN). Pre- and posttherapy tumor biopsy specimens were studied for histological changes, apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling assay), and proliferation index (Ki67). Prostate-specific membrane antigen (PSMA) expression was also evaluated using two different monoclonal antibodies to its intracellular domain (Cytogen 7E11 and Hybritech PM2). Fourteen patients with androgen-independent disease were treated with ATRA (50 mg/m2 p.o. every 8 h daily) and 16 androgen-independent and 4 androgen-dependent patients were treated with cRA inverted question markIFN (10 mg/kg/day cRA plus 3, 6, or 9 million units daily IFN). Both therapies were well tolerated, with fatigue and cheilitis being the most common adverse events. Clinical activity, assessed by radiographs and serum prostate-specific antigen, was minimal, and the majority of patients progressed within 3 months. One patient with androgen-dependent disease had prolonged stabilization for >1 year. The majority of cases (95%) showed no gross histological changes and no difference in apoptotic or proliferative indices. Increased PSMA immunoreactivity was seen in seven of nine (78%) cases using PM2 antibody and in two of nine (22%) cases using the 7E11 antibody. Although antitumor effects were modest, the results suggest a role for retinoids in modulating the expression of PSMA on prostate cancer cells. (+info)
A randomized trial of 13-Cis retinoic acid in children with advanced neuroblastoma after high-dose therapy.
One hundred and seventy-five children with Stage 3 or 4 neuroblastoma who had obtained a good response to conventional therapy were randomly allocated to 13-Cis retinoic acid at a dose of 0.75 mg/kg/day or placebo for up to 4 years. Toxicity was mild but no advantage in event-free survival was shown for the children receiving retinoic acid. (+info)
A randomized clinical trial of 4-hydroxyphenylretinamide for high-grade squamous intraepithelial lesions of the cervix.
PURPOSE: Previous trials of topical trans-retinoic acid treatment of cervical intraepithelial neoplasia (CIN) grades 2 and 3 led to a statistically significant regression of CIN 2, but not CIN 3. We tested N-(4-hydroxyphenyl)retinamide (4-HPR), a promising oral retinoid that has been shown to induce apoptosis through nonretinoic receptor acid-mediated pathways, for its toxicity and efficacy against CIN 2/3. EXPERIMENTAL DESIGN: In a blinded randomized trial, 4-HPR at 200 mg/day for 6 months (with a 3-day/month drug holiday) was compared with placebo in patients with biopsy-proven CIN-2/3 [high-grade squamous intraepithelial lesions (HGSILs)]. Patients were treated with placebo or 4-HPR for 6 months, biopsied, and then followed for an additional 6 months. At the 12-month end point, they underwent either loop excision if a histological lesion was present or a biopsy from the original area of the lesion if no lesion was present. RESULTS: An interim analysis of blinded data showed a significantly worse prognosis at 12 months for one group. When the code was broken because of the poorer outcomes, we discovered that the 4-HPR treatment arm was performing more poorly than was the placebo at 6 and 12 months (25 versus 44% response rates at 6 months; 14 versus 50% at 12 months). Toxicity was not significant in either arm. CONCLUSIONS: 4-HPR at 200 mg/day with a 3-day/month drug holiday is not active compared with placebo in the treatment of HGSIL. Because 4-HPR is active in the laboratory, the lack of effect in our trial may indicate that higher doses are needed in patients to achieve comparable results. (+info)
Paying more than lip service to lip lesions.
OBJECTIVE: To review the epidemiology, etiology, diagnosis, management, and prognosis of the most common, potentially lethal, lip lesions: leukoplakia, actinic cheilitis, and squamous cell carcinoma (SCC). QUALITY OF EVIDENCE MEDLINE: was searched from 1966 to 2002 for English-language articles on prevalence of lip lesions. No articles for a family physician audience were found. MEDLINE was searched again using the terms "leukoplakia," "actinic cheilitis," and "squamous cell carcinoma." Randomized, controlled trials were selected; non-blinded trials, population-based studies, and systematic reviews were also used. MAIN MESSAGE: Leukoplakia, actinic cheilitis, and SCC of the lips are relatively common presentations that can cause substantial morbidity and, more rarely, mortality. Any abnormality of the lips can be an embarrassment. Because of the seriousness and frequency of lip disease, it is important to look for, diagnose, and treat lip lesions to prevent morbidity and mortality and also to maintain social acceptance and self-esteem. CONCLUSION: Knowledge of leukoplakia, actinic cheilitis, and SCC of the lips will aid family physicians in diagnosing and managing these lesions and in preventing associated morbidity and mortality. (+info)
Miescher's cheilitis granulomatosa. A presentation of five cases.
Miescher's cheilitis granulomatosa (CG) consists of the appearance of recurrent labial edema on one or both lips, which can become persistent. It has traditionally been considered as a monosymptomatic form of the Melkersson-Rosenthal syndrome, described as the association of recurrent labial and/or recurrent facial edema, relapsing facial paralysis and fissured tongue. The aim of this study is to present a series of five clinically and histopathologically diagnosed cases of CG that came to our clinic at the Teaching Unit of Oral Medicine, Faculty of Medicine and Odontology, University of Murcia. A complete study of these patients evaluated the age, sex, family history, and location and course of the signs and symptoms. Various complementary examinations were carried out, studying the hematic characteristics (hemogram, erythrocyte sedimentation rate, leukocyte count), including immunological and histopathological studies. The treatment consisted of intralesional corticoids, combined in some cases with anti-leprous drugs or systemic corticoids. A good response to treatment was obtained in all cases. (+info)
Serious cutaneous adverse reactions to traditional Chinese medicines.
INTRODUCTION: Serious cutaneous adverse reactions to traditional medicines are not well described or reported in the literature, despite growing use of these medicines. METHODS: This is a case series of four patients who were found to have various serious cutaneous adverse reactions to the traditional Chinese medicines that they had taken. RESULTS: In this series, there was a patient with toxic epidermal necrolysis from traditional Chinese medicine, another with acute generalised exanthematous pustulosis from piroxicam and salicylate-contaminated traditional Chinese medicine, and two patients with drug hypersensitivity syndrome--one from traditional Chinese medicine and the other from phenylbutazone-adulterated traditional Chinese medicine. CONCLUSION: The series illustrates that serious cutaneous adverse reactions do occur with traditional medicines and emphasises the importance of being aware of such reactions. (+info)
Actinic cheilitis adjacent to squamous carcinoma of the lips as an indicator of prognosis.
Many studies have shown an association between actinic cheilitis and squamous carcinoma of the lips. AIM: The aim of the study was to observe the relation between actinic cheilitis and the prognosis of squamous carcinoma of the lips. MATERIALS AND METHODS This is a retrospective cross-sectional cohort study of squamous carcinoma of the lips. Histological sections of squamous carcinoma tumors done at the the Department of Pathology of the Sao Paulo Federal University between 1993 and 2000 were reviewed for evidence of actinic cheilitis in the lip vermillion adjacent to the tumor. Patient reports were reviewed to find information about exposure to sun, metastases and relapses. The occurrence or absence of relapses and metastases was correlated with the presence or absence of actinic cheilitis in the lip vermillion. Data was analyzed by Fisher's Exact test. RESULTS: Of the 31 selected patients, most were caucasian, males and with lower lip involvement. Statistical analysis demonstrated independence between the occurrence of metastases and relapse and gender, skin color and site (lower or upper lips). There was dependence between actinic cheilitis and solar elastosis, and between the absence of actinic cheilitis and the occurrence of metastases. There was no dependence between the absence of actinic cheilitis and the occurrence of relapses. CONCLUSION: It may be concluded that tumors originating from actinic cheilitis have a better prognosis. (+info)
Chronic relapsing allergic contact cheilitis from a toothpaste. A case report.
The paper describes the case of a 25 year-old caucasian man whose cheilitis was initially erroneously diagnosed and treated as herpetic cheilitis, and was then correctly identified as a toothpaste allergic contact cheilitis. The remission of the pathology was achieved through the elimination of the allergen, while the clinical symptoms were controlled by means of topic application of corticosteroids, with a complete and stable restitutio ad integrum of the perioral tissues. (+info)