M. Di Seri

Weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) as first-line chemotherapy for elderly patients with advanced gastric cancer: results of a phase II trial

BackgroundElderly patients have been often excluded from or underrepresented in the study populations of combination chemotherapy trials. The primary end point of this study was to determine the response rate and the toxicity of the weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) regimen in elderly patients with advanced gastric cancer. The secondary objective was to measure the time to disease progression and the survival time.MethodsChemotherapy-naive patients with advanced gastric cancer aged 70 or older were considered eligible for study entry. Patients received weekly oxaliplatin 40 mg/m2, fluorouracil 500 mg/m2 and folinic acid 250 mg/m2. All drugs were given intravenously on a day-1 schedule.ResultsA total of 42 elderly patients were enrolled. Median age was 73 years and all patients had metastatic disease. The response rate according to RECIST criteria was 45.2% (95% CIs: 30%–56%) with two complete responses, 17 partial responses, 13 stable diseases and 10 progressions, for an overall tumor rate control of 76.2% (32 patients). Toxicity was generally mild and only three patients discontinued treatment because of treatment related adverse events. The most common treatment-related grade 3/4 adverse events were fatigue (7.1%), diarrhoea (4.8%), mucositis (2.4%), neurotoxicity (2.4%) and neutropenia (4.8%). The median response duration was 5.3 months (95% CIs: 2.13 – 7.34), the median time to disease progression was 5.0 months (95% CIs: 3.75 – 6.25) and the median survival time was 9.0 months (95% CIs: 6.18 – 11.82).ConclusionOXALF represents an active and well-tolerated treatment modality for elderly patients with locally advanced and metastatic gastric cancer.

Detection of Hepatic Metastases from Colorectal Cancer: Prospective Evaluation of Gray Scale US Versus SonoVue® Low Mechanical Index Real Time-Enhanced US as Compared with Multidetector-CT or Gd-BOPTA-MRI

PURPOSE To compare ultrasound (US), low-mechanical index contrast enhanced US (CEUS) and multidetector-CT (MDCT) for the detection of hepatic metastases from colorectal cancer. METHODS AND MATERIALS From January to June 2006, 110 patients (65 males, 45 females; mean age 62 years; range 39-78) with suspected hepatic lesions from colorectal cancer were prospectively evaluated with US, CEUS and MDCT by two independent readers. Intraoperative ultrasonography (IOUS, n = 45) or a follow-up up for at least 6 months by using MDCT or Gd-BOPTA-enhanced MRI was considered the gold standard. McNemar test was employed. RESULTS Reference standards revealed 430 metastases in 110 patients. On a patient-by-patients analysis, CEUS improved US sensitivity from 67.4-71.6% to 93.4-95.8% (p < 0.05). On a lesion-by-lesion analysis, CEUS improved the sensitivity of US from 60.9-64.9% to 85.3-92.8% (p < 0.001). The specificity increased from 50-60% to 76.7-83.3%. No significant differences in sensitivity or specificity between CEUS and MDCT were found. Contrast-enhanced US was significantly more sensitive than baseline US in the detection of metastases smaller than 1 cm (p < 0.001) with an increase in sensitivity from 29.1-35% to 63.3-76.6% no significant statistical difference was identified when compared with MDCT (sensitivity of 73.3-75.8%). CONCLUSIONS CEUS is significantly more accurate than US and highly comparable with MDCT in the detection of liver metastases from colorectal cancer. Therefore, in the evaluation of patients with suspected hepatic metastases from colorectal tumour, US examination must be performed after contrast administration.

Long-term maintenance bacille Calmette-Guérin therapy in high-grade superficial bladder cancer.

OBJECTIVES To assess the long-term results of intravesical bacille Calmette-Guérin (BCG) induction plus long-term maintenance treatment for high-grade superficial bladder cancer. METHODS Between 1994 and 2000, 41 patients who presented to our clinic with superficial urothelial carcinoma of the bladder (T1G3, T1G3 plus carcinoma in situ, or recurrent TaG2-3) were treated by transurethral resection of all visible tumor and an induction cycle of BCG plus a long-term maintenance BCG course consisting of 11 monthly instillations followed by 4 quarterly instillations and then by 6 six-monthly instillations. The median follow-up was 40 months. RESULTS Thirty patients remained tumor free throughout the follow-up period. Ten patients had a recurrence of superficial tumor, 9 patients during the monthly instillation course and 1 patient during the quarterly instillation course. One patient presented with progression. CONCLUSIONS Adjuvant immunotherapy with BCG after complete transurethral resection of bladder tumor represents a highly effective primary treatment for high-grade superficial bladder cancer. Our maintenance course of BCG seemed to improve the worldwide accepted effectiveness of the BCG induction course without any important side effects.

Safety and efficacy of oral vinorelbine and capecitabine combination for metastatic breast cancer

Abstract The aim of this prospective open-label study was to evaluate the efficacy and safety of oral vinorelbine in combination with capecitabine in patients with metastatic breast cancer (MBC). 51 patients with MBC received oral vinorelbine and capecitabine. the safety profile was analyzed through NCI-CTCAE v3.0 and response was evaluated using RECIST criteria. The overall response rate was 37.2%: there were four complete responders (8%) and fifteen partial responders (29.4%); practically all the responders were patients previously treated with anthracyclines and taxanes. Sixteen patients (31.3%) experienced stable disease. the clinical benefit rate was 68.5%. The median time to progression was 8 months (range 2-43; 95% CI: 6-10.8). Vinorelbine in combination with capecitabine is an effective and safe schedule for patients with MBC especially after pretreatment with anthracycline/taxane-based regimens. The clinical benefit suggests that this may be a promising schedule in the MBC initial treatment.

Biomolecular, biochemical, and radiologic evaluation and safety of chemotherapy with bevacizumab in treatment of patients affected by mCRC.

e14140 Background: Bevacizumab (BEV) combined with chemotherapy prolongs PFS and OS in treatment of mCRC regardless of KRAS status. This study investigated statistical significance of BEV clinical benefit (CB) in treatment of mCRC according to KRAS status and metastatic sites.We evaluated timing of response through correlation between tumor markers values (MKS) and clinical responses. Most severe toxicities were observed. METHODS 108 patients were treated with first-line Folfiri or FolFoX and BEV. KRAS status was detected. Before therapy patients were investigated with CT scan and with blood sample to define MKS; MKS after 2 months of chemotherapy and CT scan after 3 months were performed. Statistical analysis has benefited from chi-square test. RESULTS Overall response rate (RR) of 42% and CB of 82% were obtained, with correlation between MKS and clinical response of 90%. 49% of population presented only hepatic metastases while 51% showed multiple metastatic sites. RR in exclusive hepatic metastatic group was 48% vs 35% multiple metastatic sites (p=0.15), CB was 90% vs 71% respectively (p=0.01). KRAS mutations were investigated in 100 patients. 65 patients were wild-type (wt 65%) while 35 patients were mutated (mut 35%). RR in wt group was 51% vs 29% in mut (p=0.03), while CB was 86% vs 80% respectively (p=0.42). Correlation between MKS and clinical response was 91% in wt group vs 93% in mut. 72 patients (66%) experienced any grade toxicities. Most common G3-G4 toxicities were neutropenia (16%), diarrhea (4%) and vomiting (2%). G1-G2 BEV toxicities were bleeding (13%), hypertension (10%), deep vein thrombosis (5%), proteinuria (2%) and pulmonary embolism (1%); no G3-G4 toxicities were showed. CONCLUSIONS RR in KRAS groups was different with an advantage, statistical significant, in KRAS wt, but this difference does not observe in CB. BEV provides significant RR and CB after short time of treatment and MKS are optimal parameters of early clinical response. BEV provides statistical significant CB in patients with only hepatic metastases vs patients with multiple metastatic sites. Treatment with BEV was well tolerated.

What caused gastrointestinal bleeding in a woman with a history of pleural mesothelioma? Metastatic diffuse epithelioid mesothelioma.

A 72-year-old white woman was admitted to the university hospital with malaria. Her medical history highlighted a pleural mesothelioma diagnosed 2 years earlier and treated by left thoracotomy with chest wall and diaphragm resection followed by four courses of …