We measured tyrosinase mRNA levels by real-time quantitative reverse transcription-PCR (qRT-PCR), in the blood of patients with uveal melanoma. Results were correlated with clinical data and, in a subgroup of patients, with the number of circulating tumor cells (CTC) assessed using isolation by size of epithelial tumor cells (ISET). Forty-one patients with uveal melanoma were longitudinally investigated over a period of 5 years. The standard curve of the qRT-PCR method used melanoma cell line SK-MEL-28, added to the blood of normal donors and it was calibrated on a synthetic RNA standard (1 SK-MEL-28 cell corresponding to 18 tyrosinase mRNA copies) to improve the procedural standardization to facilitate the comparison of data collected at different laboratories. Increased tyrosinase mRNA levels were found in at least one of the blood samples in 20 of 41 (49%) uveal melanoma patients (median 0.8 SK-MEL-28 cell equivalents/ml blood; range 0.1-14.4). A significant correlation was found between mRNA tyrosinase levels and tumor dimension (P<0.01), disease-free and overall survival (P<0.05). CTC were isolated by ISET in five of 16 patients (5.8, 2.33, 2.00, 1.25, and 0.75 CTC/ml of blood) and the corresponding tyrosinase mRNA levels were 2.13, 1.37, 0.83, 0.58, and 0.35 SK-MEL-28 cell equivalents/ml of blood. Tyrosinase was undetectable in 11 ISET-negative patients. Tyrosinase assay by qRT-PCR is a noninvasive method for the detection of tumor progression in uveal melanoma patients. The mRNA tyrosinase levels can be taken as an indirect parameter correlated to the number of CTC isolated from blood by ISET.

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The association between oxaliplatin and 5-fluorouracil (5-FU) has been extensively reported to improve prognosis of gastric cancer patients. The present study is aimed at evaluating response rate and the toxicity profile of the association with oxaliplatin, 5-FU/ lecovorin and epirubicin in gastric cancer patients with locally advanced or metastatic disease. Thirty-six patients have been enrolled and 35 evaluated. The treatment schedule was oxaliplatin (100 mg m À2 ), 5-FU (400 mg m À2 ), leucovorin (40 mg m À2 ) and epirubicin (60 mg m À2 ) intravenously. administered every 3 weeks for 6 months, for a total of 185 therapy cycles . Response rate and toxicity were assessed according to the international WHO criteria. Every patient received a mean of 5.3 therapy cycles in a day-hospital setting. Sixteen of 35 patients (46%) showed an objective response, two complete response and 14 partial response. Median time to progression was 33 weeks with an overall median survival of 49 weeks. During the study, anaemia grade 3 and neutropenia grade 3 were observed in 9 and 11% of patients respectively. A grade 3 periferic sensorial neuropathy was observed in 6% of patients. No life threatening or cardiac toxicity was recorded. The regimen used showed anticancer activity against gastric carcinoma, a tolerable toxicity profile and excellent patient compliance.

The purpose of the study was to evaluate objective response rate, survival and toxicity of the combination of gemcitabine-docetaxel administered on a biweekly schedule as first-line treatment in advanced/relapsed or metastatic urothelial carcinoma. Treatment consisted of the sequenced administration of gemcitabine 1500 mg/m(2) and docetaxel 60 mg/m(2) (2 h intravenous infusion) on days 1, 14 of a 28-day cycle for 6 months. A total of 33 patients, 22 men and 11 women, were enrolled, aged 41-75 years (median 64 years). The majority of patients had a good performance status (94%; status<2). Thirteen patients had locally advanced disease (39%) and 20 metastasic disease (41%). A total of 178 treatment cycles were administered with a median number of 5.4 cycles for a patients (range 2-8). Toxicity was primarily hematologic with the most frequent grade >2 being neutropenia (11%), with three episodes of febrile neutropenia. Anemia and thrombocytopenia were milder and had a lower incidence. The most frequent nonhematological toxicities were alopecia, followed by asthenia. Cardiac and pulmonary toxicity was minimal. No toxic deaths were recorded during study and follow-up. Overall response rate was 53.1%, including four complete responses (12.5%) and 13 partial responses (40.6%), whereas six patients (18.8%) had disease stabilization. Median time to progression was 10.2 months (95% confidence interval: 5.1-13.7), with a median survival of 14.8 months (95% confidence interval: 9.4-20.2) after an observation of 30 months (range 4-30+). The results of this study suggested that combination therapy with gemcitabine and docetaxel administered twice a week is particularly active and well tolerated as first-line treatment in advanced and/or metastatic urothelial carcinoma. Once data are confirmed in a larger study and longer follow-up, the favorable toxicity profile of this regimen may offer an interesting alternative to the cisplatin-based regimen.

Single-agent gemcitabine has been established as standard treatment for advanced pancreatic cancer since clinical studies have shown an improvement in overall survival and significant clinical benefit when compared to the best supportive care despite low overall objective response. Several phase II studies have tested other single agents and different gemcitabine-based regimens in pancreatic cancer, but both response and survival rates have remained low. Irinotecan, a topoisomerase I inhibitor currently approved for the treatment of metastatic colon cancer, has also demonstrated improved response rate in patients with pancreatic cancer. Our purpose was to determine the activity and toxicity of this regimen in patients with unresectable or metastatic pancreatic cancer. Patients with histologically confirmed pancreatic adenocarcinoma received gemcitabine 1000 mg/m2 plus irinotecan 100 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle for 6-8 months. From February 2004 to April 2006, 33 patients were entered into this study, 32 of whom were evaluable for treatment response, toxicity, median time to progression, and median survival. Characteristics included a median age of 63 years (range 41-79), 21 males (64%), and 12 females (36%). One patient discontinued treatment due to adverse effects. The total number of cycles administered was 188 and the median number of cycles for patients was 5.6 (range 2-7). Thirty-two patients were assessable for toxicity and response. Grade 3 hematological toxicity occurred in 9% of patients and was primarily neutropenia. No grade >2 gastrointestinal toxicities or death due to treatment were observed. The most frequent nonhematological adverse event was fatigue. Ten patients responded to treatment with two complete responses (6.3%) and eight partial responses (25.0%), for an overall response rate of 31.3%; 11 patients achieved stable disease (34.3%). The median time to tumor progression and the median survival were 9.2 (95% CI: 6.0-12.4) and 11.8 (95% CI: 7.7-15.9) months, respectively, with a 2-year survival of 22%. On the basis of this trial, the combination of gemcitabine plus irinotecan, administered in a weekly schedule and at this dose, is well tolerated and offers encouraging activity in the treatment of advanced and/or metastatic pancreatic cancer.