Targeting tyrosine-kinases in ovarian cancer.

INTRODUCTION: Epithelial ovarian cancer (EOC) is the leading cause of gynaecologic cancer death. Although in some cases initial treatment is effective, most of the women diagnosed with EOC will probably need medical treatment for their disease. There is a critical need to develop effective new strategies for the management of patients with advanced or recurrent EOC, and targeted therapy with tyrosine kinase inhibitors (TKIs) has continued to be an area of active research and development in this setting. AREAS COVERED: This review summarises the available evidence on the use of TKIs in the clinical management of women with EOC. This article consists of material obtained via Medline, PubMed and EMBASE literature searches up to March 2013. EXPERT OPINION: Several Phase I/II and III trials evaluated TKIs in EOC; however, it is difficult to draw conclusions on the efficacy of TKI regimens in these patients. TKIs seem to be better tolerated than conventional chemotherapy with a different toxicity profile. A better understanding of the signalling pathways, the toxicity profiles, the potential pharmacokinetic interactions as well as the identification of predictive biomarkers are needed to better identify a targeted patient population before these agents become part of routine treatment

Targeting tyrosine-kinases in ovarian cancer.

INTRODUCTION: Epithelial ovarian cancer (EOC) is the leading cause of gynaecologic cancer death. Although in some cases initial treatment is effective, most of the women diagnosed with EOC will probably need medical treatment for their disease. There is a critical need to develop effective new strategies for the management of patients with advanced or recurrent EOC, and targeted therapy with tyrosine kinase inhibitors (TKIs) has continued to be an area of active research and development in this setting. AREAS COVERED: This review summarises the available evidence on the use of TKIs in the clinical management of women with EOC. This article consists of material obtained via Medline, PubMed and EMBASE literature searches up to March 2013. EXPERT OPINION: Several Phase I/II and III trials evaluated TKIs in EOC; however, it is difficult to draw conclusions on the efficacy of TKI regimens in these patients. TKIs seem to be better tolerated than conventional chemotherapy with a different toxicity profile. A better understanding of the signalling pathways, the toxicity profiles, the potential pharmacokinetic interactions as well as the identification of predictive biomarkers are needed to better identify a targeted patient population before these agents become part of routine treatment

Modification of ultrasonographically measured endometrial thickness afterdiscontinuation of adjuvant therapy with tamoxifen in postmenopausal breastcancer patients.

INTRODUCTION: The aim of this study was to evaluate endometrial changes after five years of tamoxifen treatment by measuring endometrial thickness with transvaginal ultrasonography. MATERIALS AND METHODS: Fifty-five asymptomatic postmenopausal women who had assumed tamoxifen, 20 mg daily, for five years were controlled six months after discontinuation of the therapy. Of these 42 were followed-up at 12 months. Statistical analysis was performed using the analysis of variance for repeated measures and the Anova test; p < 0.05 was considered statistically significant. RESULTS: We found a significant reduction in endometrial thickness at six months (p = 0.0046) and at 12 months (p = 0.0003) but not between six and 12 months (p = 0.06). CONCLUSION: A statistically significant reduction in endometrial thickness after discontinuation of tamoxifen therapy was found. This can probably be attributed to the cessation of the estrogenic side-effects of tamoxifen therapy

Chemotherapy with cisplatin and paclitaxel in locally advanced cervical cancer:has this regimen still a role as neoadjuvant setting?

AIM: Neoadjuvant chemotherapy represents a promising alternative to concomitant chemo-radiation therapy in locally advanced cervical cancer patients. The aim of this study was the evaluation of pathologic response rates, toxicity and predictors of response in locally advanced cervical cancer patients treated with neoadjuvant cisplatin and paclitaxel followed by radical surgery. METHODS: Fourteen patients with stage IB2 to IIB cervical cancer received three cycles of cisplatin 75 mg/m2 and paclitaxel 175 mg/m2 intravenously every three weeks followed by radical hysterectomy and bilateral pelvic lymphadenectomy. Toxicity, pathologic response and predictors of response were evaluated. RESULTS: Chemotherapy related toxicities we-re as follows: alopecia 100%, asthenia 35.7%; nausea and vomiting 14.3%; paclitaxel hypersensitivity 7.1%, neutropenia 7.1%. Optimal, partial and no pathologic response was achieved in 21.4%, 64.3% and 14.2% of the patients, respectively. Based on lack of pathologic risk factors, 43% of the patients did not receive any adjuvant radiotherapy. Better response rates were obtained in patients with stage IIB, tumor diameter <5 cm, Hb >12 g/dL and SCC antigen <1.5 mg/dL. None of these variables reached statistical significance. CONCLUSION: Neoadjuvant chemotherapy with cisplatin and paclitaxel in locally advanced cervical cancer appeared to be well-tolerated. Even though the TIP regimen has been shown to be more effective than the TP regimen in randomized controlled prospective trial, the TP regimen remains a reasonable alternative in those patients in whom the TIP regimen is considered or shown to be too toxic

Endometrial carcinoma during tamoxifen therapy. A case report [Adenocarcinoma dell'endometrio insorto durante terapia con tamoxifene: Descrizione di un caso clinico.]

Tamoxifen is a non-steroid estrogenic antagonist, used in post-surgical therapy of breast cancer. It interferes with endocrinous promotion of breast cancer. Tamoxifen could determine endometrial, even carcinomatous, alterations. The case of a postmenopausal patient surgically treated for breast cancer and successively treated with tamoxifen (20 mg/die), is reported. She underwent ultrasonographic and hysterosonographic endometrial evaluation and finally a hysterectomy with bilateral annessiectomy. This case seems to confirm tamoxifen possible carcinogenical effects on the endometrium

Lymphedema microsurgical preventive healing approach for primary prevention of lower limb lymphedema after inguinofemoral lymphadenectomy for vulvar cancer.

OBJECTIVE: Lower limb lymphedema (LLL) is the most disabling adverse effect of surgical treatment of vulvar cancer. This study describes the use of microsurgical lymphatic venous anastomosis (LVA) to prevent LLL in patients with vulvar cancer undergoing inguinofemoral lymph node dissection (ILND). METHODS: The study included 8 patients with invasive carcinoma of the vulva who underwent unilateral or bilateral ILND. Before incision of the skin in the inguinal region, blue dye was injected in the thigh muscles to identify the lymphatic vessels draining the leg. Lymphatic venous anastomosis was performed by inserting the blue lymphatics coming from the lower limb into one of the collateral branches of the femoral vein (telescopic end-to-end anastomosis). An historical control group of 7 patients, which underwent ILND without LVA, was used as comparison. After 1 month from the surgery, all patients underwent a lymphoscintigraphy. RESULTS: In the study group, 4 patients underwent bilateral ILND, and 4 patients underwent unilateral ILND. Blue-dyed lymphatics and nodes were identified in all patients. It was possible to perform LVA in all the patients. The mean (SD) time required to perform a monolateral LVA was 23.1 (3.6) minutes (range, 17-32 minutes). The mean (SD) follow-up was 16.7 (6.2) months; there was only 1 case of grade 1 lymphedema of the right leg. Lymphoscintigraphic results showed a total mean transport index were 9.08 and 14.54 in the study and the control groups, respectively (P = 0.092). CONCLUSIONS: This study shows for the first time the feasibility of LVA in patients with vulvar cancer undergoing ILND. Future studies including larger series of patients should clarify whether this microsurgical technique reduces the incidence of LLL after ILND

Intraoperative frozen section risk assessment accurately tailors the surgical staging in patients affected by early-stage endometrial cancer: the application of 2 different risk algorithms.

ObjectiveThe aim of this study was to investigate the frozen section (FS) accuracy in tailoring the surgical staging of patients affected by endometrial cancer, using 2 different risk classifications.Methods/MaterialsA retrospective analysis of 331 women affected by type I endometrial cancer and submitted to FS assessment at the time of surgery. Pathologic features were examined on the frozen and permanent sections according to both the GOG33 and the Mayo Clinic algorithms. We compared the 2 models through the determination of Landis and Koch kappa statistics, concordance rate, sensitivity, specificity, positive predictive value, and negative predictive value for each risk algorithm, to assess whether there are differences in FS accuracy depending on the model used.ResultsThe observed agreement between the frozen and permanent sections was respectively good (k = 0.790) for the GOG33 and optimal (k = 0.810) for the Mayo classification. Applying the GOG33 algorithm, 20 patients (6.7%) were moved to an upper risk status, and 20 (6.7%) were moved to a lower risk status on the permanent section; the concordance rate was 86.5%. With the Mayo Clinic algorithm, discordant cases between frozen and permanent sections were 19 (7.6%), and the risk of lymphatic spread was underestimated only in 1 case (0.4%); the concordance rate was 92.4%. The sensitivity, specificity, positive predictive value, and negative predictive value for the GOG33 were 92%, 94%, 92%, and 93%, whereas with the Mayo algorithm, these were 98%, 91%, 77%, and 99%, respectively.ConclusionsAccording to higher correlation rate and observed agreement (92.4% vs 86.5% and k = 0.810 vs 0.790, respectively), the Mayo Clinic algorithm minimizes the number of patients undertreated at the time of surgery than the GOG33 classification and can be adopted as an FS algorithm to tailor the surgical treatment of early-stage endometrial cancer even in different centers.</jats:sec