isotretinoin and Uterine-Cervical-Dysplasia

Topics: Adult; Aged; Antiretroviral Therapy, Highly Active; Female; Follow-Up Studies; HIV Infections; Humans; Hysterectomy; Isotretinoin; Middle Aged; Neoplasm Recurrence, Local; New Orleans; Socioeconomic Factors; Treatment Outcome; Uterine Cervical Dysplasia

To estimate the efficacy of isotretinoin for prevention of progression of low-grade squamous intraepithelial lesions (SIL) of the cervix to high-grade lesions or invasive cervical cancer; to estimate the regression rate of low-grade SIL with isotretinoin and the toxicity of isotretinoin in this setting; and to correlate serum CD4 levels with progression of low-grade SIL.. A randomized, phase III, observation-controlled, multicenter trial was performed in which 117 human immunodeficiency virus (HIV)-positive women with low-grade SIL of the cervix received either oral isotretinoin at 0.5 mg/kg per day for 6 months or observation. Papanicolaou smears and colposcopy/biopsy were done at regular intervals during follow-up. The primary endpoint was progression to high-grade SIL or cervical cancer.. Twenty-one of 102 women (20.6%) completing follow-up experienced progression to high-grade SIL, 13 in the observation group and eight in the isotretinoin group. This difference was not significant (P =.29). No cases of invasive cancer were seen. Baseline CD4 levels were lower than anticipated (median 329 cells/mm(3)), but not associated with time to progression (P =.36). Most subjects (63 of 102, 61.7%) used highly active antiretroviral therapy. Subjects under age 30 were more likely to progress than those older than 30 (P =.046).. Isotretinoin was not associated with longer time to progression of low-grade SIL. This appears to be a chronic condition in HIV-positive women, with a low risk of progression and significant rate of resolution. As in the general population, observation without excisional therapy may be appropriate for HIV-positive women with low-grade SIL.

Topics: Adult; CD4 Lymphocyte Count; Disease Progression; Female; HIV Infections; Humans; Isotretinoin; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Topics: Administration, Oral; Adult; Antineoplastic Agents; Chemoprevention; Colposcopy; Conization; Dose-Response Relationship, Drug; Female; Humans; Isotretinoin; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Treatment Failure; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

The purpose of this study was to determine whether the progression of low-grade squamous intraepithelial lesions of the cervix in women with the human immunodeficiency virus can be predicted reliably by standard cytologic testing.. As part of a previously reported trial, 288 biopsy specimens were collected from 117 women with the human immunodeficiency virus. These specimens underwent central and local interpretation, which were compared and correlated with cytologic results. Ninety-two subjects had matched cytologic/histologic pairs at study termination, which were compared to determine whether cytologic testing was predictive of progression.. Of the central histologic interpretations, 26 of 288 interpretations (9%) differed from local results, 97 of 246 cytologic/histologic pairs (39%) were discordant, and 21 subjects had progression to high-grade squamous intraepithelial lesions by histologic evidence. Cytologic testing showed high-grade squamous intraepithelial lesions in 4 of 21 specimens (sensitivity, 19%). The remaining cytologic specimens were either low-grade squamous intraepithelial lesions or were normal.. This substudy of pathologic results from a randomized clinical trial suggests that, although the risk of progression of low-grade squamous intraepithelial lesions is low, follow-up cytologic testing is unreliable. Colposcopic evaluation with directed biopsies should be continued.

Topics: Antineoplastic Agents; Biopsy; Carcinoma, Squamous Cell; Cervix Uteri; Clinical Trials, Phase III as Topic; Colposcopy; Disease Progression; Female; Follow-Up Studies; HIV Infections; Humans; Isotretinoin; Predictive Value of Tests; Prognosis; Randomized Controlled Trials as Topic; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears

Vulvar intraepithelial neoplasias are difficult to eradicate completely without extensive surgical intervention. Cidofovir, a deoxycytidine monophosphate analog, may have a therapeutic role in this disease. A 43-year-old woman with a 20-year history of genital warts presented with extensive vulvar intraepithelial neoplasia III, and refused surgical resection. Topical cidofovir 1% in Beeler base completely eradicated the lesion. Successive treatment applications, however, were necessary. Cidofovir is a promising topical antiviral compound for HPV induced vulvar intraepithelial neoplasia.

Topics: Administration, Oral; Administration, Topical; Adult; Antineoplastic Agents; Carcinoma in Situ; Cidofovir; Cytosine; Drug Resistance, Multiple; Female; Humans; Injections, Subcutaneous; Interferons; Isotretinoin; Neoplasm Recurrence, Local; Organophosphonates; Organophosphorus Compounds; Uterine Cervical Dysplasia; Vulvar Neoplasms

Retinoids (RA) and interferon (IFN) have been reported to be active against a variety of tumors and human papillomavirus (HPV)-related lesions. Because chronic and recurrent HPV-linked vulvar intraepithelial neoplasia 3 (VIN 3) have a high risk of invasion, we evaluated combined therapy of IFN-alpha with 13-cis-retinoic acid (13 cRA) in the treatment of two VIN 3 cases of this type.. Two patients with chronic and recurrent VIN 3 were treated with combined therapy of IFN-alpha (4.5 x 10(6) five times a week) and 13 cRA (1 mg/kg/d) for six months. Clinical regression was observed at the end of treatment in both cases, but histologic features of VIN 3 were still present.. These data demonstrate the ineffectiveness of the combined regimen of IFN-alpha and 13 cRA with this schedule for a period of six months in recurrent and chronic VIN 3.

Topics: Adult; Drug Therapy, Combination; Female; Humans; Interferon-alpha; Isotretinoin; Keratolytic Agents; Middle Aged; Papillomaviridae; Papillomavirus Infections; Treatment Failure; Treatment Outcome; Uterine Cervical Dysplasia; Vulva; Vulvar Neoplasms

Investigation of retinoids for anticancer activity in humans, either in the chemopreventive or treatment mode, has been little studied. We summarize here our ongoing investigations in four different areas: (1) secondary prevention of cervical dysplasia with topical application of all-trans-retinoic acid; (2) adjuvant treatment of resected high-risk stage I and II malignant melanoma with bacille Calmette Guérin (BCG) plus or minus oral vitamin A; (3) topical vitamin A acid therapy for cutaneous metastatic melanoma; an (4) oral isotretinoin as an anticancer agent.

Topics: Diterpenes; Female; Humans; Isomerism; Isotretinoin; Melanoma; Neoplasms; Palmitates; Retinyl Esters; Skin Neoplasms; Tretinoin; Uterine Cervical Dysplasia; Vitamin A