Complete response after imatinib mesylate administration in a patient with chemoresistant stage IV seminoma.

The case of a young man with stage IV chemoresistant pure seminoma overexpressing KIT, who achieved complete remission (CR) after the administration of imatinib mesylate (400 mg once daily), along with a third-line chemotherapy regimen, consisting of paclitaxel (150 mg/m2), oxaliplatin (100 mg/m2) and gemcitabine (800 mg/m2) every 2 weeks with granulocyte colony-stimulating factor (G-CSF) support is reported. The patient had received first- and second-line regimens consisting of ifosfamide, bleomycin, etoposide cisplatin (5 cycles, every 3 weeks) and methotrexate, vinblastine, actinomycin D, cyclophosphamide, cisplatin (3 cycles, every 3 weeks) respectively, without having normalized beta-human chorionic gonadotrophin (beta-HCG) levels. Following treatment with imatinib plus third-line chemotherapy (paclitaxel, oxaliplatin, gemcitabine), the levels of beta-HCG were reduced to within the normal limits during the first month of treatment. Therefore, the patient underwent surgical resection of the residual disease from the retroperitoneum and liver, which proved to be only necrotic tissue. The patient is under close follow-up, with no evidence of disease, 36 months after the completion of chemotherapy and 32 months post surgery.

Kit expression in male germ cell tumors.

OBJECTIVE: KIT functions as the receptor for stem cell factor (SCF) and this interaction is essential for regulation of proliferation and survival, particularly for germ cells since it regulates oogenesis, folliculogenesis and spermatogenesis. Up-regulation of KIT signalling has been associated with oncogenic transformation in cells expressing the molecule. Our objective was to investigate the expression of KIT in germ cell tumor patients and correlate it with the patients' clinical characteristics. PATIENTS AND METHODS: One hundred and seventy-three archival blocks of formalin fixed, paraffin-embedded tumor samples from histologically confirmed germ cell tumor (GCT) patients were included in the study. Immunohistochemical staining for KIT was performed and the percentage of positive cells was calculated by an independent pathologist. KIT expression was considered as positive if > 10% of tumor cells displayed membranous or cytoplasmic staining. RESULTS: Sixty-one patients with seminomatous (49 pure, 11 anaplastic, 1 spermocytic) and 112 with non-seminomatous GCTs (36 malignant teratoma undifferentiated (MTU), 15 malignant teratoma trophoblastic (MTT), 20 malignant teratoma intermediate (MTI), 35 malignant teratoma combined (MTC) and six others) were identified. Among pure seminoma patients, 38 (77.5%) revealed a positive staining for KIT, while only two out of eleven (18.2%) anaplastic seminoma patients were identified as positive. This difference was statistically significant (p < 0.001). Among 35 patients with an MTC, 48.6% had a positive KIT staining while only two of the remaining patients with a non-seminomatous GCT had a positive staining. Although KIT was strongly correlated with seminomatous histology (p < 0.001), it failed to correlate with stage (p = 0.19) or treatment response (p = 0.11) in these patients. Overall, four (one seminoma, three MTC) out of 22 chemoresistant patients showed a positive staining for KIT. CONCLUSION: KIT is expressed in the majority of seminomas and in seminomatous components of the combined tumors, but only in a minority of anaplastic seminomas and rarely in non-seminomatous GCTs. The recent development of tyrosine kinase inhibitors may offer a possibility of cure in chemoresistant patients overexpressing KIT.

Epithelial ovarian carcinoma in younger vs older women: is age an independent prognostic factor? The Hellenic Oncology Cooperative Group experience.

We retrospectively investigated the outcome of epithelial ovarian cancer (EOC) in women less than 45 years and over 70 years treated with cisplatin-based chemotherapy. We also investigated the impact of various factors on patients' survival. The tumor registry of the Hellenic Cooperative Oncology Group was used to identify women less than 45 years and over 70 years with EOC diagnosed between 1979 and 2004. Survival was calculated by the Kaplan-Meier method, and Cox proportional hazard models were used to determine the independent effect of each variable on survival. Of 1748 EOC patients, 200 were 45 or younger and 282 were over 70 years old. In the univariate analysis, younger age (P < 0.001), better performance status (PS) (P < 0.001), early stage (P < 0.001), 0-2 cm residual disease (P < 0.001), and well or moderate differentiation grade (P= 0.004) were significant prognostic factors for improved survival. In the multivariate analysis, older age (hazard ratio [HR]: 1.88, 95% CI: 1.27-2.77, P= 0.002), advanced stage (HR: 2.87, 95% CI: 1.49-5.52, P= 0.002), PS >1 (HR: 1.91, 95% CI: 1.18-3.08, P= 0.008), and residual disease (HR: 1.46, 95% CI: 1.01-2.13, P= 0.046) were independently associated with inferior survival. With a median follow-up of 45 months (range 0.1-197 months), median survival (118.5 months) of younger patients differed significantly compared to that of older patients (33 months) (P < 0.001). In conclusion, younger women with EOC have significantly improved survival compared to older patients. Age, PS, stage of the disease at diagnosis, and residual disease are important independent predictors for survival.

Cisplatin-based chemotherapy for merkel cell carcinoma of the skin.

PURPOSE: Merkel cell carcinoma (MCC), a rare tumor of the skin with aggressive behavior, is usually fatal when advanced disease is present. The role of chemotherapy (CT) in the treatment of patients with MCC is unclear. METHODS: Over 15 years, 9 patients with locally advanced or metastatic disease were treated with carboplatin (CBDCA) (300 mg/m(2) of AUC 5 on Day 1) and etoposide (VP-16) (100 mg/m(2) on Days 1-3) every 3 weeks. As second-line CT, cisplatin (CDDP) (60-100 mg/m(2)), ifosfamide (IFO) (3-5 g/m(2)) and epirubicin (EPI) (30-50 mg/m(2)) were utilized. RESULTS: Of the 3 patients who received adjuvant therapy, one achieved complete response after 108+ months with second-line chemotherapy and radiotherapy, despite a brief relapse; 2 patients remain disease-free after 84+ and 108+ months. Of the 6 patients with locally advanced or metastatic disease who were treated with first-line chemotherapy, one (16.6 percent) achieved a complete response and 3 (50 percent) achieved partial response, for an overall response rate of 66.6 percent. Two patients (one with complete and one with partial response) received subsequent radiotherapy, following which complete response was achieved. Of the 2 complete responders, one patient remains disease-free after 56+ months. The median overall survival from the time of initial diagnosis for the whole group was 56 months (range 15-114 months); the median overall survival from the initiation of chemotherapy was 18 months (range 6-108+). Local recurrences and soft tissue metastases responded better than visceral metastases. Patients with partial response and no response had rapid disease progression and fatality, despite second-line chemotherapy and/or radiotherapy. CONCLUSION: MCC appears to be chemosensitive but can progress rapidly with fatal outcomes. Although the rarity of these tumors precludes randomized trials, a common treatment plan should be utilized by those treating MCC. This may allow some conclusions regarding the optimum treatment of patients with MCC to be drawn in the future.

Systemic chemotherapy in locally advanced and/or metastatic bladder cancer.

Transitional cell carcinoma of the bladder is a common malignancy. Advanced urothelial cancer is a chemosenstive neoplasm. Whereas the MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen was long-considered the standard of care for patients with advanced disease, the evaluation of newer agents with retained activity and improved tolerability has been the focus of much investigation over the past decade. Combinations such as cisplatin-gemcitabine (GC) and intensified, G-CSF supported MVAC have shown more favourable toxicity profile and equal or even improved efficacy. Specific groups of patients (elderly, patients with renal dysfunction or poor performance status or co-morbidities) who cannot tolerate cisplatin-based therapy, should receive carboplatin, gemcitabine or taxane-based treatment. Continuing improvements in our understanding of the molecular phenotype of individual patient tumors may lead to the appropriate therapies that target molecular aberrations unique to this malignancy. This review will summarize recent developments in the management of locally advanced (T4b, N 2-3) and/or metastatic (M1) bladder cancer.

Dermatomyositis associated with breast cancer.

An increased risk of underlying malignancy has been found in patients with dermatomyositis (DM). The risk is increased even in patients with DM aged 45 or younger and remains high for many years after diagnosis. Breast carcinoma does not represent the most common solid tumor associated with this autoimmune disorder. In the present report, two new cases of DM associated with breast cancer are described, together with an extensive literature review.