AMNIOTE PHYLOGENY AND THE IMPORTANCE OF FOSSILS

Several prominent cladists have questioned the importance of fossils in phylogenctic inference, and it is becoming increasingly popular to simply fit extinct forms, if they are considered at all, to a cladogram of Recent taxa. Gardiner's (1982) and LØvtrup's (1985) study of amniote phylogeny exemplifies this differential treatment, and we focused on that group of organisms to test the proposition that fossils cannot overturn a theory of relationships based only on the Recent biota. Our parsimony analysis of amniote phylogeny, special knowledge contributed by fossils being scrupulously avoided, led to the following best fitting classification, which is similar to the novel hypothesis Gardiner published: (lepidosaurs (turtles (mammals (birds, crocodiles)))). However, adding fossils resulted in a markedly different most parsimonious cladogram of the extant taxa: (mammals (turtles (lepidosaurs (birds, crocodiles)))). That classification is like the traditional hypothesis, and it provides a better fit to the stratigraphic record. To isolate the extinct taxa responsible for the latter classification, the data were successively partitioned with each phylogenetic analysis, and we concluded that: (1) the ingroup, not the outgroup, fossils were important; (2) synapsid, not reptile, fossils were pivotal; (3) certain synapsid fossils, not the earliest or latest, were responsible. The critical nature of the synapsid fossils seemed to lie in the particular combination of primitive and derived character slates they exhibited. Classifying those fossils, along with mammals, as the sister group to the lineage consisting of birds and crocodiles resulted in a relatively poor fit to data; one involving a 2—4 fold increase in evolutionary reversals! Thus, the importance of the critical fossils, collectively or individually, seems to reside in their relative primitive-ness, and the simplest explanation for their more conservative nature is that they have had less time to evolve. While fossils may be important in phylogenetic inference only under certain conditions, there is no compelling reason to prejudge their contribution. We urge systematists to evaluate fairly all of the available evidence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73857/1/j.1096-0031.1988.tb00514.x.pd

The impact of low grade toxicity in older people with cancer undergoing chemotherapy

BACKGROUND: Significant toxicity in chemotherapy trials is usually defined as grade ⩾3. In clinical practice, however, multiple lower grade toxicities are often considered meaningful. The purpose of this observational cohort study was to identify which level of toxicity triggers treatment modification and early discontinuation of chemotherapy in older people. METHODS: Patients aged 65+ were recruited in a central London hospital. A total of 108 patients were recruited at the start of new chemotherapy treatment between October 2010 and July 2012. RESULTS: Mean age was 72.1±5 years, median 72 and range 65–86 years. Of the patients, 50.9% (55) were male with gastrointestinal (49), gynaecological (18), lung (15) and other cancers (26). Chemotherapy was palliative in 59.3% (64/108), curative/ neoadjuvant/adjuvant in the others. Mean number of cycles completed was 4.2±3. Treatment modifications due to toxicity occurred in 60 (55.6%) patients, 35% (21/60) of whom had no greater than grade 2 toxicity. Early treatment discontinuation because of toxicity occurred in 23 patients (21.3%), 39.1% (9/23) of whom had no greater than grade 2 toxicity. CONCLUSIONS: Many older patients did not complete treatment as planned. Treatment was modified/discontinued even for one or two low-grade toxicities. Further work is required to clarify whether low-grade toxicity has a greater clinical impact in older people, or whether clinicians have a lower threshold for modifying/discontinuing treatment in older people

Multicenter randomized phase III trial comparing protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin in inoperable pancreatic cancer

Purpose: To compare protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin (MMC) in patients with advanced pancreatic cancer in a multicenter, prospectively randomized study.Patients and Methods: Two hundred eight patients were randomized to PVI 5-FU (300 mg/m2/d for a maximum of 24 weeks) or PVI 5-FU plus MMC (7 mg/m2 every 6 weeks for four courses). The major end points were tumor response, survival, toxicity, and quality of life (QOL).Results: The two treatment groups were balanced for baseline demographic factors, and 62% had metastatic disease. The overall response rate was 8.4% (95% confidence interval [CI]) 3.2% to 13.7% for patients treated with PVI 5-FU alone compared with 17.6%; 95% CI 10.3% to 25.1% for PVI 5-FU plus MMC (P = .04). Median failure-free survival was 2.8 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC (P = .14). Median survival was 5.1 months for PVI 5-FU and 6.5 months for PVI 5-FU plus MMC (P = .34). Toxicities in both arms were mild. There was an increased incidence of neutropenia in the 5-FU plus MMC arm (P < .01), although no differences in infection were seen. No patients developed hemolytic uremic syndrome. Global QOL improved significantly after 24 weeks of treatment compared with baseline for patients receiving 5-FU plus MMC, although there was no statistically significant difference in QOL between arms.Conclusion: PVI 5-FU plus MMC resulted in a superior response rate in comparison with PVI 5-FU alone in advanced pancreatic cancer, but this did not translate into a survival advantage. These results emphasize the importance of chemotherapy in this setting and the continuing value of the fluoropyrimidines in pancreatic cancer