Neoadjuvant gemcitabine and cisplatin followed by radical surgery in (bulky) squamous cell carcinoma of cervix stage IB2.

OBJECTIVES: This study aimed to evaluate the efficacy and toxicity of gemcitabine in combination with cisplatin as neoadjuvant therapy in patients with cervical carcinoma stage IB2. PATIENTS AND METHODS: Chemotherapy-naive patients with histologic diagnosis of squamous cell cervical carcinoma staged as IB2 were treated with 2 cycles of cisplatin (70 mg/m(2) on day 1) and gemcitabine (1000 mg/m(2) on days 1 and 8), given every 21 days. After chemotherapy, patients underwent radical hysterectomy and pelvic lymphadenectomy. Patients judged to have a non-resectable disease were treated with standard pelvic radiation. RESULTS: Between September 2000 to March 2004, 28 patients were enrolled in the study, of which 27 were evaluable for efficacy and toxicity. The mean age was 39 years (30-55). The overall clinical response rate was 88.9% (24/27), with complete response (CR) in 9/27 patients (33.3%) and partial response in 15/27 patients (55.5%). Three patients (11.1%) did not respond and nobody progressed. A pathological CR was noted in 2 of 24 patients who underwent radical surgery. The 3 non-responding patients were subsequently treated with radiation and achieved CR. Grades 3 or 4 neutropenia, anemia, or thrombocytopenia was observed in 18.5%, 7.4%, and 3.7% patients respectively. Non-hematological toxicity was mild except grade 3 nausea/vomiting in 18.5% patients. At median follow-up time of 36.7 months (range 7-51 months), the 3-year survival was 88.9%. CONCLUSION: Neoadjuvant treatment with gemcitabine/cisplatin combination for patients with cervical cancer (stage IB2) appears encouraging, with manageable and acceptable toxicity profile.

Successful treatment of recurrent vulvar intraepithelial neoplasia resistant to interferon and isotretinoin with cidofovir.

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.

Estrogen replacement therapy and ovarian cancer.

Estrogen replacement therapy (ERT) has been shown to be of benefit for menopausal women, especially in prevention of coronary heart disease and osteoporotic fractures. Cancer fear is an important obstacle to use of ERT. From our literature review, there is a weak or no association between ERT and ovarian cancer risk. Individual risk of cancer should be considered before ERT use. The second issue in this review is ERT in patients with ovarian cancer. The majority of patients with ovarian cancer are postmenopausal or become menopausal after surgery. ERT is considered by many physicians to be contraindicated in patients with cancer. However, there is evidence that ERT in selected cancer patients may be of benefit for survival and quality of life. After weighing the evidence from studies on ERT in patients with ovarian, breast or endometrial cancer, we propose the use of ERT in selected ovarian cancer patients who are suffering from or are at a high risk of debilitating menopausal symptoms, osteoporosis, and coronary heart disease. The benefit of ERT to selected patient's health and quality of life appears to outweigh the risk of cancer recurrence.

Docetaxel for patients with paclitaxel-resistant Müllerian carcinoma.

PURPOSE: To determine the efficacy and toxicity of docetaxel in patients with müllerian carcinoma resistant to paclitaxel. PATIENTS AND METHODS: Thirty-two patients with epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who failed paclitaxel-based chemotherapy received either 100 or 75 mg/m(2) of docetaxel every 3 weeks. Resistance to paclitaxel was defined as either progression of disease during treatment, failure to achieve regression of disease after at least four courses, or rapid recurrence (within 6 months) after completion of therapy. RESULTS: Eighteen patients were treated on a formal protocol and fourteen with the commercially available docetaxel. Thirty were assessable for response. Toxicities were thoroughly evaluated in the 18 patients on protocol. Twenty-seven patients (85%) had epithelial ovarian cancer. The overall response rate was 23% (one complete and six partial responses), with a median survival time of 44 weeks (9.5 months). Nine patients had stable disease and 14 progressive disease. Among 19 patients who progressed during prior paclitaxel treatment, two (11%) responded to docetaxel, compared with five (45%) of 11 patients in other paclitaxel-resistance categories. The responders had a median taxane-free interval (ie, the time between the last paclitaxel and first docetaxel treatment) of 73 weeks, compared with 19 weeks for the nonresponder group. Toxic effects were as expected. CONCLUSION: Docetaxel is an active chemotherapeutic agent in patients with müllerian carcinoma previously treated with paclitaxel-based chemotherapy, especially in the patients who had a long taxane-free interval after a previous short response to paclitaxel.

Folate binding protein peptide 191-199 presented on dendritic cells can stimulate CTL from ovarian and breast cancer patients.

Tumor associated lymphocytes (TAL) isolated from malignant ascites cultured in media containing interleukin-2 show antitumor responses. These antitumor responses are mediated by cytotoxic T lymphocytes (CTL) which recognize antigen in the context of MHC molecules using T cell receptors. CD8+ CTL recognize peptide epitopes processed from cellular proteins in the context of MHC class I molecules. These peptides have a restricted length of 8-11 amino acids. The folate binding protein (FBP) is overexpressed in over 90% of ovarian and 20-50% of breast cancers. We recently found that FBP is the source of antigenic peptides recognized by a number of these CTL-TAL. This indicated that FBP peptides are antigenic in vivo for ovarian and breast CTL-TAL. To define FBP immunogenicity, a peptide defining the epitope E39 (FBP, 191-199) was presented by PMBC derived dendritic cells (DC) from healthy donors isolated by the CD14 method to ovarian and breast CTL-TAL. Stimulation of ovarian and breast CTL-TAL by E39 pulsed DC (DC-E39), in the presence of IL-2, rapidly enhanced or induced E39 specific CTL activity. This E39-responder population consisted of cells expressing TCR V beta 9, V beta 13, and V beta 17 families, based on the increase in the percentages of these families in DC-E39 versus DC-NP stimulated TAL. Characterization of immunogenic tumor antigens and of cytokine requirements for induction of functional antitumor effectors may be important for future cancer vaccine developments.

Long-acting triptorelin for the treatment of endometriosis.

OBJECTIVE: To evaluate the efficacy and adverse effects of monthly triptorelin injection for the treatment of endometriosis. METHODS: A multicenter clinical trial including 45 women with endometriosis, treated with triptorelin 3.75 mg i.m. every 4 weeks in six consecutive doses. The main outcome measures were symptom relief, reduction according to revised American Fertility Society (rAFS) scores, reduction in size of ovarian endometrioma, effects on hormone and lipid profiles, changes in bone mineral density (BMD), adverse effects, and return of menstruation. Data were analyzed using repeated measures analysis of variance and paired t-tests. RESULTS: Pain-related symptoms decreased in all cases after 8 weeks of treatment. Laparoscopic assessment revealed a reduction in rAFS scores in 21 out of 25 cases (mean pretreatment scores 43.44 +/- 5.75 vs. post-treatment scores 22.30 +/- 3.40, P < 0.001). The size of ovarian endometrioma decreased in eight of nine women but none disappeared. Serum luteinizing hormone, follicle-stimulating hormone and estradiol levels were effectively suppressed during treatment. A slight increase in cholesterol and triglyceride levels was observed but all values were within normal limits. After 24 weeks of treatment there was a slight decrease in BMD of total body, lumbar vertebrae and femoral neck but not radius. The main adverse effects included hot flushes, night sweating, vaginal dryness, headache, dizziness and nausea Menstruation returned 83.76 +/- 2.91 days after the last injection of triptorelin. CONCLUSION: Long-acting triptorelin is efficacious in the treatment of endometriosis and has tolerable side effects.