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

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.

Weekly combination of non-pegylated liposomal doxorubicin and taxane in first-line breast cancer: wALT trial (phase I-II).

BACKGROUND: Through different pharmacodynamic-kinetic interactions, weekly administration of proved efficacy agents can overcome resistance with lower toxicity and greater benefit. Based on this assumption, we designed a phase I-II trial with weekly non-pegylated liposomal anthracycline and taxane in first-line breast cancer patients. PATIENTS AND METHODS: We enrolled 56 previously untreated metastatic breast cancer patients; they were randomly assigned to receive paclitaxel (Taxol) (50 mg/mq) or docetaxel (Taxotere) (30 mg/mq) combined with non-pegylated liposomal anthracycline (25 mg/mq) on days 1, 8 and 15 every 4 weeks. The primary end points were the clinical benefit and treatment-related toxic effects assessment. Secondary end points were time-to-disease progression (TTP) and overall survival (OS). RESULTS: The overall clinical benefit was 87.04%. World Health Organization G3-4 toxic effects included neutropenia (45%), anemia (44%), complete alopecia (83%), severe onycholysis and neuropathy. The 24% of patients developed left ventricular ejection fraction reduction but none >10% with recover after treatment completion. The median absolute decrease from baseline was 1%. Median TTP was 11 months and median OS was 23 months. CONCLUSIONS: Combined weekly administration of taxane and non-pegylated liposomal anthracycline is well tolerated and clinical benefit data encourage phase III study design.

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.

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.

BACKGROUND: Elderly 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. METHODS: Chemotherapy-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. RESULTS: A 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). CONCLUSION: OXALF represents an active and well-tolerated treatment modality for elderly patients with locally advanced and metastatic gastric cancer.

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.

The role of hypoxic stop-flow perfusion and high dose chemotherapy in the treatment of regionally advanced colorectal cancer.

The primary or secondary forms of colorectal cancers involving local structures or spreading in the abdomen or pelvic area without extra-regional metastases are identified as regionally advanced colorectal cancers (RACRC). They are unresectable and thus radiotherapy and chemotherapy are the fundamental treatment methods. However, these regimens have failed to check the diffusion of tumor satisfactorily in most forms of RACRC. The abdominal and pelvic regions can be isolated from corporal circulation by temporary occlusion of the aorta and cava and perfused with high doses of chemotherapeutic drugs. The hypoxic abdominal or pelvic stop-flow method for delivering high-dose antiblastic agents to these body districts to avoid toxicity by chemofiltration has been suggested. This study examines the possibility of using this method to treat various forms of RACRC.

Immunoblot analysis of Salmonella typhi lipopolysaccharide (LPS) using typhoid sera.

Lipopolysaccharide (LPS) of Salmonella typhi has been analyzed by immunoblotting with pooled sera from typhoid patients. Pooled typhoid sera have recognized all the antigenic determinants of S. typhi LPS, giving a strong reaction with the repeating units on the O-side chains as well as with the core region. Cross-reacting antigens have been observed with the LPS of S. typhimurium and S. enteritidis, while no heterologous reactions were seen with the LPS of E. coli strains.

[Research on staphylococcal enterotoxin B by dot immunobinding assay (DIB). Preliminary observations]. / Ricerca della enterotossina B stafilococcica mediante dot immunobinding assay (DIB). Osservazioni preliminari.

A recently developed immunoenzymatic technique, the Dot Immunobinding assay (DIB), has been applied to the rapid detection of staphylococcal enterotoxin B in filtered culture supernatants. The test has been shown to be highly sensitive and specific, easy to perform and rapid (only 4 hours). The use of nitrocellulose paper as the solid phase allows the exact standardization of the amount of antigen employed and it avoids the overnight incubation usually necessary with the conventional enzyme-linked immunosorbent assay (ELISA).

[The enzyme-linked immunosorbent assay (ELISA) test in the immunodiagnosis of urinary schistosomiasis. Comparison with the indirect haemagglutination (IH) and counterimmunoelectrophoresis (CIEP) (author's transl)]. / Il test ELISA nella diagnosi immunologica della schistosomiasi urinaria. Confronto con le tecniche di emoagglutinazione indiretta e di counterimmunoelettroforesi.

Sera from patients with urinary schistosomiasis were used to compare the sensitivity and specificity of the ELISA, IH and CIEP tests for the detection of antibodies to schistosomes. Sera from persons with parasitic infections other than schistosomiasis, and sera from healthy persons were used as negative controls. The ELISA test was more sensitive than the IH and CIEP, and slightly more specific than the CIEP. This simple test may be suitable for use in large seroepidemiological surveys.