Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma.

BACKGROUND: Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone. No language restrictions were imposed. OBJECTIVES: To compare the effects of therapy with chemotherapy and immunotherapy (chemoimmunotherapy) versus chemotherapy alone in people with metastatic malignant melanoma. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (14 February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to 30 January 2006 ), EMBASE (2003 to 20 July 2005) and LILACS (1982 to 20 February 2006). References, conference proceedings, and databases of ongoing trials were also used to locate trials. SELECTION CRITERIA: All randomised controlled trials that compared the use of chemotherapy versus chemoimmunotherapy on people of any age, diagnosed with metastatic melanoma. DATA COLLECTION AND ANALYSIS: Two authors independently assessed each study to determine whether it met the pre-defined selection criteria, with differences being resolved through discussion with the review team. Two authors independently extracted the data from the articles using data extraction forms. Quality assessment included an evaluation of various components associated with biased estimates of treatment effect. Whenever possible, a meta-analysis was performed on the extracted data, in order to calculate a weighed treatment effect across trials. MAIN RESULTS: Eighteen studies met our criteria and were included in the meta-analysis, with a total of 2625 participants. We found evidence of an increase of objective response rates in people treated with chemoimmunotherapy, in comparison with people treated with chemotherapy. Nevertheless, the impact of these increased response rates was not translated into a survival benefit. We found no difference in survival to support the addition of immunotherapy to chemotherapy in the systemic treatment of metastatic melanoma, with a hazard ratio of 0.89 (95% CI 0.72 to 1.11, p=0.31). Additionally, we found increased hematological and non-hematological toxicities in people treated with chemoimmunotherapy. AUTHORS' CONCLUSIONS: We failed to find any clear evidence that the addition of immunotherapy to chemotherapy increases survival of people with metastatic melanoma. Further use of combined immunotherapy and chemotherapy should only be done in the context of clinical trials.

Colony stimulating factors for chemotherapy induced febrile neutropenia.

BACKGROUND: Febrile neutropenia is a frequent event for cancer patients undergoing chemotherapy and it is potentially a life threatening situation. The current treatment is supportive care plus antibiotics. Colony stimulating factors (CSF) are cytokines that stimulate and accelerate the production of one or more cellular lines in bone marrow. Some clinical trials addressed the question of whether the addition of CSF to antibiotics (ATB) could improve the outcomes of patients with febrile neutropenia. The results of these trials are conflicting and no definitive conclusion could be reached. OBJECTIVES: To evaluate the safety and effectiveness of adding colony stimulating factors to ATB when treating febrile neutropenia caused by cancer chemotherapy. SEARCH STRATEGY: The search covered the major electronic databases: CANCERLIT, EMBASE, LILACS, MEDLINE, SCI and The Cochrane Controlled Trials Register. Experts were consulted and references from the relevant articles scanned. SELECTION CRITERIA: We looked for all randomized controlled trials (RCTs) that compare CSF plus antibiotics versus antibiotics alone for the treatment of established febrile neutropenia in adults and children. DATA COLLECTION AND ANALYSIS: Two of the reviewers independently selected, critically appraised and extracted data from the studies. A meta-analysis of the select studies was performed, using Review Manager. MAIN RESULTS: More than 8000 references were screened. Thirteen studies were included. The overall mortality was not influenced by the use of CSF [Odds Ratio (OR) = 0.68; 95% Confidence Interval (CI) = 0.43 to 1.08; p=0.1]. A marginally significant result was obtained for the use of CSF in reducing infection related mortality [OR= 0.51; 95% CI = 0.26 to 1.00; p=0.05], but this result was highly influenced by one study. When this study is excluded from our analysis, this possible benefit disappears [OR= 0.85; 95% CI = 0.33 to 2.20; p= 0.7]. The group of patients treated with CSF had a shorter length of hospitalization [Hazard Ratio (HR) = 0.63; 95% CI = 0.49 to 0.82; p=0.0006] and a shorter time to neutrophil recovery [HR= 0.32; 95% CI = 0.23 to 0.46; p < 0.00001]. REVIEWER'S CONCLUSIONS: The use of CSF in patients with febrile neutropenia due to cancer chemotherapy does not affect overall mortality, but reduces the amount of time spent in hospital and the neutrophil recovery period. It was not clear whether CSF has an effect on infection-related mortality.

Bamboozled again! Inadvertent isolation of fungal rDNA sequences from bamboos (Poaceae: Bambusoideae).

Polymerase chain reaction (PCR) amplification of the nuclear internal transcribed spacer (ITS) and 5.8S regions of rDNA from woody bamboos (Bambuseae) led to the recovery of fungal instead of bamboo sequences under a variety of PCR conditions and irrespective of whether the plant DNA was extracted from fresh leaves or silica gel-dried material. Phylogenetic analyses based on the 5.8S sequences indicated that the fungi were most likely basidiomycetes and that none was an ascomycete. A diverse assemblage of nonascomycetous fungi was isolated from different bamboos, and various fungi coexisted in the same host plant. There was no evidence that closely related fungi consistently associate with closely related host bamboos. Phylogenetic analysis based on 5.8S sequences showed that some fungi were in lineages near Volvariella, Lentinula, Peniophora, and Rhizoctonia, but the insufficiency of basidiomycete and zygomycete ITS sequences in sequence data bases precluded more precise fungal identifications. Bamboo ITS regions were amplified only when fresh leaves were surface sterilized before DNA extraction, suggesting that the fungal associates are epiphyllous rather than endophytic. This study highlights the possibility of inadvertent PCR amplification of contaminating DNAs in molecular phylogenetic studies, particularly when using "universal" amplification primers.

Comparisons of the molecular evolutionary process at rbcL and ndhF in the grass family (Poaceae).

We examine rate heterogeneity among evolutionary lineages of the grass family at two plasmid loci, ndhF and rbcL, and we introduce a method to determine whether patterns of rate heterogeneity are correlated between loci. We show both that rates of synonymous evolution are heterogeneous among grass lineages and that are heterogeneity is correlated between loci at synonymous sites. At nonsynonymous sites, the pattern of rate heterogeneity is not correlated between loci, primarily due to an aberrant pattern of rate heterogeneity at nonsynonymous sites of rbcL. We compare patterns of synonymous rate heterogeneity to predictors based on the generation time effect and the speciation rate hypotheses. Although there is some evidence for generation time effects, neither generation time effects nor speciation rates appear to be sufficient to explain patterns of rate heterogeneity in the grass plastid sequences.

Molecular evolution and phylogenetic utility of the chloroplast rpl16 intron in Chusquea and the Bambusoideae (Poaceae).

Phylogenetic relationships within Chusquea, a diverse genus of neotropical woody bamboos, and among selected members of the Bambusoideae were explored using rpl16 intron sequence data from the chloroplast genome. Mechanisms of mutation, including slipped-strand mispairing, secondary structure, minute inversions, and base substitutions, were examined within the rpl16 intron, and their effects on sequence alignment and phylogenetic analysis were investigated. Thirty-five bamboo sequences were generated and two separate matrices were analyzed using maximum parsimony. In the first, 23 sequences from Chusquea, 1 of Neurolepis, and 3 outgroups were included. Neurolepis was supported as sister to Chusquea, Chusquea was strongly supported as a monophyletic lineage, and three species of Chusquea subg. Rettbergia were resolved as the most basal clade within the genus. In the second analysis, 15 sequences, 14 from across the subfamily and 1 outgroup, were included. A Bambusoideae clade was recovered with the Olyreae/Parianeae (herbaceous bamboos) and the Bambuseae (woody bamboos) each supported as monophyletic. Two clades corresponding to temperate and tropical woody bamboos were derived within the Bambuseae and the tropical taxa were further split into New World and Old World clades. The rpl16 intron in bamboos was found to be susceptible to frequent length mutations of multiple origins, nonindependent character evolution, and regions of high mutability, all of which created difficulties in alignment and phylogenetic analysis; nonetheless the rpl16 intron is phylogenetically informative at the inter- and intrageneric levels in bamboos.