Matrix metalloproteinases and proangiogenic factors in testicular germ cell tumors.

PURPOSE: Testicular cancer is the most frequent solid tumor in young male adults and a disease with elusive pathogenesis. The purpose of this study was to determine the role of matrix metalloproteinases and angiogenic factors in the pathogenesis of testicular germ cell tumors (GCTs). METHODS: Between 2003 and 2006 we measured the serum levels of matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), vascular endothelial growth factor A (VEGF-A), basic fibroblast growth factor (bFGF), platelet derived growth factor BB (PDGF-BB) and angiopoietin 2 (Ang-2) in 50 patients with testicular GCTs, at baseline, one month after the completion of the second cycle of chemotherapy and one year after the completion of chemotherapy, and in 16 male age-matched controls at baseline. RESULTS: At baseline, mean TIMP-2 value was lower in patients than controls, mean MMP-2/TIMP-2 ratio was higher in patients than controls and MMP9/TIMP-2 ratio was also higher. Ang-2 value was higher in patients than controls and bFGF value was also higher. Comparisons of the same parameters were also made among the 3 consecutive serum samples of the patients. All parameters normalized after chemotherapy except Ang-2 which remained elevated. CONCLUSION: The present study supports the hypothesis that tumor invasion and angiogenesis play a role in testicular GCTs pathogenesis. Also an interesting hypothesis was formed, concerning the role of elevated levels of Ang-2 found in testicular GCTs patients in the pathogenesis of the increased long term cardiovascular morbidity of these patients. Larger prospective studies are needed to confirm our results.

Adult granulosa cell tumors of the ovary: a clinicopathological study of 34 patients by the Hellenic Cooperative Oncology Group (HeCOG).

BACKGROUND: Granulosa cell tumors (GCT) are rare malignant neoplasms of the ovaries with, usually, indolent biological behavior. PATIENTS AND METHODS: The epidemiological, clinical and pathological features of 34 patients with adult GCT, from the registry of the HeCOG, were analyzed retrospectively for their prognostic significance. RESULTS: The median age was 51 years with post- to premenopausal ratio=l.8 and median size of the tumor 10 cm. Forty-seven % had a low mitotic index (1-3 mitoses/10 high-power fields, HPFs) and 48% had International Federation of Obstetrics and Gynecology (FIGO) stage IA. After 34.5 months of median follow-up, the estimated 5-year and 10-year progression-free survival (PFS) was 78% and 65%, respectively, while both the 5- and 10-year overall survival (OS) was 89%. The stage and the presence of residual disease after surgery had prognostic significance for OS in the univariate analysis. Out of 19 patients whose disease was completely resected, the median disease-free survival (DFS) was 11 months. Only rupture of the tumor during surgery had prognostic significance for DFS in the univariate analysis. Seven out of 13 evaluable patients with unresectable disease responded to first-line chemotherapy (CT), 6 of them completely, while three patients responded to second-line chemotherapy. All the responders were retreated with platinum-based CT and one of them was platinum-insensitive. All the patients receiving second-line non-platinum CT developed progressive disease (PD). CONCLUSION: The only curative treatment of GCT is complete surgical resection of all visible disease, while platinum-based CT is the most effective first-line, as well as second-line treatment.

Neoadjuvant chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy for larynx preservation in patients with advanced laryngeal cancer.

PURPOSE: The efficacy and toxicity of neoadjuvant chemotherapy followed by radiotherapy and concurrent chemoradiotherapy and their impact on larynx preservation have been studied in patients with advanced (stage III, IVa, and IVb) squamous cell cancer of the larynx. PATIENTS AND METHODS: Fifty patients were treated with either 2-4 cycles of induction chemotherapy with cisplatin 100 mg/m(2), day 1 and infusional 5-fluorouracil (5-FU 1000 mg/m(2), days 1-5), followed by radiotherapy 70 Gy, 1.8-2 Gy per fraction, or concurrent chemoradiotherapy (the above-mentioned radiotherapy concurrently with carboplatin 300 mg/m(2) every 21 days or weekly paclitaxel 80 mg/m(2)). Patients were allocated in the 2 arms by 1:1 selection. At the end of both protocols, patients without complete response (CR) underwent laryngectomy and/or neck lymph node dissection. Assessed were response and toxicity rates, overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 31 (62%) patients achieved larynx preservation with acceptable organ function. No statistically significant difference in response rate and OS was found between the two treatment arms. Patients submitted to concurrent chemoradiotherapy showed significantly longer DFS (14 vs. 10 months, p= 0.0397) and higher rates of larynx preservation (p <0.05). All grade IV side effects occurred in the concurrent chemoradiotherapy group. CONCLUSION: Concurrent compared to alternating chemoradiotherapy was more toxic, but achieved significantly longer DFS and higher rate of larynx preservation.

A phase III randomized study comparing paclitaxel and cisplatin versus cyclophosphamide and cisplatin in patients with advanced ovarian cancer.

AIM: To assess progression-free survival (PFS) and overall survival (OS) in patients with advanced epithelial ovarian cancer receiving the combination of cisplatin (75 mg/m(2) i.v.) and cyclophosphamide (700 mg/m(2) i.v.) (CP), or the combination of paclitaxel (175 mg/m2) followed by cisplatin (75 mg/m2) (TP). PATIENTS AND METHODS: One hundred and twenty patients were randomized to receive six cycles of one of the treatments every 3 weeks. If measurable, complete response (CR) or partial response (PR) was determined. RESULTS: There was a significant difference (p<0.05) in the frequency of response (CR +PR) rates between treatment groups, in favor of paclitaxel containing regimen. The median PFS was 9 months for patients in the CP group and 12 months for patients in the TP group (log-rank p=0.215). The median OS were 24 months and 20 months in TP and CP arms, respectively (log-rank p=0.350). Neutropenia and alopecia were more severe with paclitaxel-containing regimen. CONCLUSION: Although OS and PFS were similar in two arms, TP regimen yielded superior response rates relative to CP, with an acceptable toxicity profile. Therefore, the TP regimen remains the preferred initial treatment option.

A prospective randomized study of irinotecan (CPT-11), leucovorin (LV) and 5-fluorouracil (5FU) versus leucovorin and 5-fluorouracil in patients with advanced colorectal carcinoma.

The purpose of this study was to compare the activity and toxicity of an irinotecan (CPT-11), leucovorin (LV) and 5-fluorouracil (5FU) combination with a standard regimen of 5FU and LV, in patients with advanced colorectal carcinoma. One hundred and sixty patients were randomized; 80 patients (group A) received LV 20 mg/m(2) bolus i.v. and 5FU 425 mg/m(2) bolus i.v. on days 1-5, every 28 days; 80 patients (group B) received CPT-11 80 mg/m(2) (30-90 min i.v. infusion), followed by LV 20 mg/m(2) bolus i.v. and 5FU 425 mg/m(2) bolus i.v. on days 1, 8, 15, 22, 29, and 36, every 8 weeks. The overall response rate was 30% and 47.5% in groups A and B respectively. Progression-free survival was significantly higher in the triple-drug combination arm (median 7.5 vs. 4.5 months; p= 0. 0335). However, overall survival did not differ significantly between the two arms (15 months vs. 14 months for the groups B and A respectively; p=0.3531). The main grade 3 adverse events were diarrhea (19%, in group A vs. 35% in group B; p=0.032) and mucositis (2% vs. 14%; p=0.017). The regimen containing irinotecan showed activity in advanced colorectal cancer. The overall safety data confirm this combination as a well-tolerated treatment.

5-Fluorouracil and cisplatin in the treatment of advanced oral cancer.

The benefit of the effect of chemotherapy in patients with advanced head and neck squamous cell tumors have been demonstrated by recent meta-analyses of randomized studies. However, the role of chemotherapy-especially in advanced oral cancer-is not fully clear, because of the very small amount of phase II literature available. From January 1994 to December 2000, a total of 44 pts aged 33-75 years (mean age 60 years) with advanced and histologically proved squamous cell carcinoma's of the oral cavity received at least one chemotherapy course. Seven patients had stage III and 37 stage IV disease. The chemotherapy was the initial therapy in a group of 21 patients. In a second group of 23 patients the chemotherapy was delivered after relapse of their disease. The pre-chemotherapy treatment of the second group was radiotherapy in 11, surgery in 4, combination of radiotherapy and surgery in 8 patients. The chemotherapy regimen consisted of cisplatin 100 mg/m(2) in 3-h infusion, day 1 and 5-FU 1000 mg/m(2) in 24-h infusion, days 1-5. Treatment was repeated every 21 days. A total of 154 treatment courses (3.5 per patient, ranged 1-10) were administered. Myelotoxicity, nausea and vomiting were the major treatment complications. The overall response rate to the induction chemotherapy was 52.3%, with 19% complete (CR), and 33.3% partial response's (PR) and to the chemotherapy for recurrent/metastatic disease 30.4% with 8.7% CR, and 21.7% PR. No difference was found in the median survival of the two subgroups (12 months). The median survival of the responders was 15 months (95% CI 11.3-18.7 months), and of the non-responders 9 months (95% CI 5.6-12.4 months) (P = 0.0067). Chemotherapy with cisplatin and 5-FU combination is effective in pts with advanced squamous cell oral cancer and appears to improve the survival of patients who have a good response.

Surgical adjuvant therapy of rectal carcinoma: a controlled evaluation of leucovorin, 5-fluorouracil and radiation therapy with or without interferon-alpha2b.

BACKGROUND: The aim of this study was to determine whether the efficacy of the combination of 5-fluorouracil (5-FU), leucovorin (LV) and radiation therapy (RT) could be improved by the addition of interferon-alpha2b (IFN-alpha) in patients who have had a 'curative' resection, for rectal adenocarcinoma (Dukes' B2/C; T3 N0, T4 N0, N1-3). PATIENTS AND METHODS: A total of 207 eligible patients with a performance status of 0 or 1 were randomized postoperatively between days 21 and 70 to one of the two treatment groups: group A, LV 20 mg/m2 i.v. bolus and 5-FU 425 mg/m2 i.v. days 1-5 and 29-33, LV 20 mg/m2 and 5-FU 400 mg/m2 days 57-60 and 85-88, LV 20 mg/m2 and 5-FU 380 mg/m2 days 1-5 and 29-33 with the second day 1 occurring 28 days after the completion of RT (45 Gy); group B, LV, 5-FU and RT as in group A, and IFN-alpha 5 x 10(6) IU s.c. three times during each week chemotherapy is given. RESULTS: 104 patients were randomized into group A and 103 into group B. There was no statistically significant difference in either disease-free survival or overall survival between the two groups. Toxicity was also the same, except for the flu-like syndrome associated with the IFN-alpha administration. CONCLUSIONS: There was no difference in efficacy between the two combinations. Toxicity was greater with the LV + 5-FU + IFN-alpha regimen because of the flu-like syndrome.

Malignant cardiac tamponade in women with breast cancer treated by pericardiocentesis and intrapericardial administration of triethylenethiophosphoramide (thiotepa).

We treated 19 women with malignant cardiac tamponade due to advanced breast cancer with subxiphoid pericardiocentesis and local thiotepa instillation. The method has no serious side effects, prevents pericardial fluid reaccumulation, and, combined with systemic adjuvant therapy, prolongs survival.

Testicular tumor metastatic to the nose. A case report.

In this paper we present an uncommon tumor found in the nasal cavity, the result of a metastasis from primary tumor of testis (embryonal carcinoma) in a young patient of 24 years of age. For this uncommon tumor we discuss the case with the Greek and foreign bibliography.

Synchronous anorectal malignant melanoma and rectal adenocarcinoma: report of a case.

BACKGROUND: Synchronous neoplasms of the rectum are an uncommon condition. The situation becomes more rare when tumors are of different origin. To the authors' knowledge, synchronous anorectal melanoma and adenocarcinoma of the rectum have not been reported in the literature before. METHODS AND RESULTS: A 67-year-old female patient with synchronous anorectal malignant melanoma and adenocarcinoma of the rectum is described. She had preoperative colonoscopic diagnosis. The different neoplasms' origin was histologically proven. Surgical management consisted of abdominoperineal resection of the rectum. Postoperatively, the patient received adjuvant chemotherapy of six cycles duration. At present, the patient has completed 32 months of follow-up. There is no evidence of recurrent disease or distant metastases. CONCLUSION: Review of the literature confirms the rarity of anorectal malignant melanoma. On the other hand, the rectum represents the most common site for development of colonic adenocarcinoma. We were unable to trace synchronous presentation of these two tumors. Prognosis should be defined by the most malignant neoplasm; therefore, management should be focused on treating the melanoma.

Sialyltransferase and nucleoside diphosphatase as markers for tumor monitoring.

In this study we report serum sialyltransferase and nucleoside diphosphatase activities of patients with malignant tumors of various primary sites and extent, prior to and during chemotherapy. Enzyme levels were compared to clinical and laboratory parameters. The sialyltransferase and uridine diphosphatase (UDPase) activities in samples of 43 patients with advanced ovarian cancer was four to ten fold above the normal mean value (sialyltransferase 85.1 +/- 58 pmol/hr/ml and UDPase 26.6 +/- 7.2 nmol/hr/ml). After effective chemotherapy with adriamycin and cisplatin, the enzyme activity decreased markedly. In cases of complete remission, enzyme activity decreased to the normal range. In three cases after initial response for several months a rise of both enzymes was observed before any other biochemical finding of the forthcoming relapse. Similar patterns were observed in testicular cancer (6 cases). Clinical correlation is also obvious in other tumors except malignant lymphomas. Our findings show that the activities of these enzymes correlated with the clinical course, and therefore they can be the basis for clinical application for tumor monitoring, especially during chemotherapy.

[Chemotherapy of the non-small cell bronchogenic carcinoma]. / Chemotherapie des nicht-kleinzelligen Bronchialkarzinoms.

From 1976 to 1981 61 patients (50 men and 11 women) with non-small cell bronchogenic carcinoma (i.e. squamous cell or adeno-carcinoma) received a chemotherapy treatment based on two cytostatic drug combinations for each histological group. The drugs which were used were cyclophosphamide, adriamycin, vincristine, methotrexate, bleomycin, 5-fluorouracil and procarbazine. All patients had advanced disease and 6 of them had had previous surgical excision of the primary tumor. A large proportion of the patients had received irradiation to the primary site prior to chemotherapy. 1 patient developed a complete remission, 5 developed a partial remission and 34 showed stabilization of their disease. In 21 patients the disease progressed in spite of the treatment. Responders had a significantly longer survival than non-responding patients.