isotretinoin and Vulvar-Neoplasms

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

Patients with metastasising carcinoma of the uterine cervix or recurrent disease, in whom local treatment as surgery or radiotherapy has failed, are still an unsolved problem. Platinum-based multi-agent chemotherapies achieve overall response rates up to 60%, but side effects are serious and so far no survival benefit has been proven. Recent publications report on a synergistic effect of combination therapy using 13-cis-retinoic acid and interferon alpha-2 a in the treatment of squamous cell carcinoma of the cervix. In a pilot study we include 6 patients with locally recurrent or metastasising squamous cell carcinomas, five of the uterine cervix, one of the vulva. The systemic therapy consisted of-orally administered 13-cis-retinoic acid (80 mg q. d.) and subcutaneously injected interferon alpha-2 a (6 x 10(6) I.E. q. d.). All patients were primarily treated by surgical and/or radiation therapy. In each case chemotherapy had been either already performed or rejected by the patient. Median duration of treatment was 52 days, median survival time 107 days. Out of 6 patients 3 experienced progression of disease uninfluenced by therapy. One patient with multiple subcutaneous lymph node metastases showed mixed response for a short period of 3 weeks before progression and eventual death. One patient had no change or disease for 13 months with subsequent progression and eventual death after 22 months. One patient could not be evaluated for an allergic reaction after only 15 days of treatment. Other side effects were "flu-like symptoms", skin irritations, conjunctivitis sicca and chileitis, all WHO 1-2. Overall toxicity must be rated low compared to standard chemotherapy, but is not negligible. In our study the positive reports in literature concerning the treatment of primary advanced cervical cancer and recurrent advanced carcinoma of the skin could not be reproduced. This might be due to the small number of cases, which is a common problem in immunotherapeutic studies. Moreover, very unfavourable patient selection criteria in our study compared to primarily untreated patients may also have contributed to different response rates. However, in our opinion the tested regimen cannot be considered sufficiently effective in patients suffering from pretreated, recurrent squamous cell carcinoma of the cervix or vulva.

Topics: Administration, Oral; Adult; Aged; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Humans; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha; Isotretinoin; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Pilot Projects; Recombinant Proteins; Survival Rate; Uterine Cervical Neoplasms; Vulvar Neoplasms

Repeated topical application of 13-cis-retinoic acid resulted in complete disappearance of leukoplakia of the vulva in 8 out of 16 patients, among them 2 out of 3 with recurrence after vulvectomy. A considerable regression of leukoplakia was seen in 7 other patients, usually after 1 to 2 months of daily retinoid treatment. After 2-4 months of maintenance therapy and during 3-7 months of the follow up period no recurrences were seen. Side effects of treatment could be managed. Serum retinol level was found to be lower in patients then in healthy subjects. The results suggest that patients with chronic epithelial vulvar dystrophies could benefit from local retinoid treatment, especially in cases with advanced dystrophies until now qualified for vulvectomy.

Topics: Administration, Topical; Adult; Antineoplastic Agents; Female; Humans; Isotretinoin; Leukoplakia; Middle Aged; Tretinoin; Vulvar Neoplasms