Second-line treatment strategies for RAS wild-type colorectal cancer: A systematic review and Network Meta-analysis (NMA).

BACKGROUND: The optimal strategy for second-line (IIL) treatment in KRAS wt metastatic colorectal cancer (mCRC) is not determined yet. METHODS: A random-effect NMA of phase II/III RCTs was conducted to evaluate IIL treatment for all-RAS wt mCRC, comparing anti-EGFR or anti-VEGF, and chemotherapy (CT). RESULTS: Overall, 11 RCTs (3613 patients) were included. In KRAS wt patients, PFS was improved with anti-VEGF (HR 0.43) and anti-EGFR (HR 0.63) vs CT. However, anti-VEGF based therapy had the highest likelihood of being ranked as the best treatment in terms of PFS (SUCRA 99.3%) and OS (SUCRA 99.4%). Bevacizumab-based treatment is most likely to be the best treatment in terms of PFS (SUCRA 89.1%) and OS (SUCRA 86.7%). CONCLUSIONS: Second line treatment with anti-VEGF and anti-EGFR improved PFS in mCRC patients, however, anti-VEGF based therapy, particularly CT plus bevacizumab, is the best treatment according to SUCRA in terms of PFS and OS.

Docetaxel and oxaliplatin in the second-line treatment of platinum-sensitive recurrent ovarian cancer: a phase II study.

BACKGROUND: A prospective phase II study was conducted to evaluate the efficacy and toxicity of the combination docetaxel (Taxotere) (DTX) and oxaliplatin (OXA) in ovarian cancer patients recurring after a platinum-free interval (PFI) >12 months. PATIENTS AND METHODS: DTX, 75 mg/m(2), was administered by 60 min i.v. infusion, followed by OXA, 100 mg/m(2), given by a 2 h i.v., on day 1 every 21 days. RESULTS: From October 2003 to June 2006, 43 ovarian cancer patients were enrolled. Median PFI was 26 months. All patients were available for response evaluation: 17 complete responses and 12 partial responses were registered, for an overall response rate of 67.4%. The median response duration was 10 months. Stable disease was documented in 11 patients (median duration = 5.5 months). The median time to progression and overall survival were 14 and 28 months. A total of 259 courses were administered. Grade 3-4 leukopenia was documented in 32.5% of the patients, while no case of severe anemia and thrombocytopenia was observed. Grade 3-4 neurotoxicity and grade 2 alopecia were observed in 9.3% and 34.9% of cases, respectively. CONCLUSION: DTX/OXA combination is an active regimen with a favorable toxicity profile, for treatment of recurrent platinum-sensitive ovarian cancer patients.

Retrospective analysis of adverse drug reactions induced by gemcitabine treatment in patients with non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the world. Traditional chemotherapy for advanced NSCLC is often considered excessively toxic. Recent clinical trials documented that gemcitabine may represent a good therapeutical option in patients with NSCLC. Aim of our research was to retrospectively evaluate the adverse effects induced by gemcitabine in patients with NSCLC from 1 January 1997 to 31 December 2002, in clinical records of Oncology Divisions of "S. Giovanni di Dio" Hospital of Crotone, "Ospedali Riuniti" Hospital of Reggio Calabria, Hospital of Paola, and in Pneumological Oncology Division of "Mariano Santo" Hospital of Cosenza, Italy. Clinical records of patients treated with gemcitabine (1000mgm(-2) on days 1 and 8) were reviewed and following data were obtained: sex and age of the patients, histologic diagnosis and disease stage, World Health Organisation (WHO) performance status and toxic effects induced by gemcitabine. We reported that 71.6% of NSCLC patients (age range 48-77 years; 135 males, 27 females; performance status 0=53, 1=109) were eligible for our study. Side effect of gemcitabine involved gastrointestinal system (nausea, vomiting and diarrhoea) and only in the last cycles (VIII-XI) emopoiethic system (leukopenia, neutropenia, thrombocytopenia and anemia). Grade IV vomiting occurred in three patients, thrombocytopenia in two. Grade III leukopenia was observed in three patients. Other toxicities were mild. None of the patients died during chemotherapy. In conclusion, these data showed that gemcitabine present a very good tolerability in patients with NSCLC. Therefore, it could be considered as a new therapeutic agents to use as first line therapy for this disease.

[Plasma amino acids in patients with liver cirrhosis treated with lactulose]. / Gli aminoacidi plasmatici in pazienti con cirrosi epatica trattati con lactulosio.

The altered plasma amino acid pattern (i.e. increased levels of aromatic amino acids and decreased levels of branched chain amino acids) is a characteristic feature of cirrhotic patients. Recently it has been proved that an increased net degradation of BCAA is positively correlated to the plasma NH3 level, strongly suggesting that these amino acids are molecularly involved in glutamine synthesis to detoxify ammonia in skeletal muscle. Lactulose, a synthetic, nonabsorbable disaccharide, is believed to actively promote excretion of ammonia from the body by causing it to be trapped in the acidified fecal stream and making it unavailable for absorption. Therefore therapy with lactulose could determine an increase of BCAA. The present study was undertaken to examine plasma amino acid pattern of ten patients with liver cirrhosis before and after lactulose therapy. No statistically significant changes of amino acids were observed.

Plasma free aminoacids pattern in progressive systemic sclerosis.

20 free aminoacids levels have been measured with a chromatographic method (Beckman 118 BL Aminoacid analyzer) in 9 patients affected by progressive systemic sclerosis and in 15 healthy subjects (control group). Both patients and control group were females, mean daily protein intake was between 1,2-1,5 gr/Kg in the two groups. No other pathological condition was found in each patient, none of them was receiving drug therapy at least from 2 months. No significant age different existed between the patients and the control group. Analysis of variance of the results showed significant decreases of proline, histidine, valine and methionine levels and significant increase of aspartic acid concentration in the plasma of PSS patients.

[Blood amino acids in chronic HBsAg positive liver disease]. / Gli aminoacidi plasmatici nelle epatopatie croniche HBsAg positive.

Typical changes in blood aminoacid concentrations have been described in patients with severe liver disease. In this study we measured the serum amino acid levels, by Beckman Aminoacid Analyzer, in 11 healthy subjects and 24 HBsAg-positive patients with biopsy-proven liver disease (4 CPH, 10 CAH, 10 cirrhosis). A significant decrease in total aminoacids was observed in CAH and cirrhosis groups (-24% and -22% respectively). The three branched chain aminoacids (BCAA = val + leu + isoleu) were reduced by 24% (P less than 0.002) and 37% (P less than 0.001) in the CAH and cirrhosis groups respectively. Tyrosine was the only of the aromatic aminoacids (AAA) to increase in cirrhotics (+ 34%, P less than 0.02). The molar ratio BCAA/AAA was 3.6 in controls, 3.8 in CPH, 3.1 in CAH (P less than 0.025) and 1.9 in cirrhosis (P less than 0.001). A linear correlation was found between molar ratio BCAA/AAA and serum albumin in all patients (P less than 0.001). These results document the presence of specific quantitative changes in serum aminoacids of HBsAg positive patients, which appear related to severity of liver disease and comparable to the alterations described in non viral chronic liver disease.