Phil Mack

Purpose Erlotinib marginally improves survival when administered continuously with gemcitabine to patients with advanced pancreatic cancer; however, preclinical data suggest that there is antagonism between chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors when these are delivered concurrently. We tested a pharmacodynamic separation approach for erlotinib plus gemcitabine and interrogated EGFR signaling intermediates as potential surrogates for the efficacy of this strategy. Methods Patients with measurable, previously untreated locally advanced unresectable or metastatic pancreatic cancer were treated with gemcitabine 1000 mg/m2 as an intravenous infusion over 30-min on days 1, 8, 15 and erlotinib 150 mg/day on days 2-5, 9-12, 16-26 of each 28-day cycle. The primary endpoint was progression-free survival ; secondary endpoints included RECIST objective response rate and safety. The study was terminated after thirty patients due to funding considerations. Results The median PFS was 2.07 months and the ORR was 11 %. No unexpected safety signals were seen: the most common grade 3 or higher adverse events were neutropenia, lymphopenia, and fatigue. Patients with mutant plasma Kirsten rat sarcoma virus had significantly lower median PFS and overall survival than those without detected plasma KRAS mutations. Conclusions Although pharmacodynamically separated erlotinib and gemcitabine were feasible and tolerable in patients with advanced pancreatic cancer, no signal for increased efficacy was seen in this molecularly unselected cohort. Detection of a KRAS mutation in circulating cell-free DNA was a strong predictor of survival. © 2014 Japan Society of Clinical Oncology.

Does a white philosopher have anything of value to offer to the philosophy of race and racism? If this philosophical subfield must embrace subjective experience, why should we value the perspective of white philosophers whose racial identity is often occluded by racial normativity and who lack substantive experiences of being on the receiving end of racism? Further, if we should be committed to experience, in what sense can the philosophy of race and racism be “objective”? What should that word mean?Tackling this question first, “objective” should at least mean general, that the ideas of the literature can be coherently integrated. An objective take on racism brings together a plurality of perspectives. What’s wrong with just a plurality of satellite ideas? It implies a fragmented approach to ameliorating racism, where different specialists have different recommendations. How can racism, generally, be lessened? If major views of racism are unifiable, then we have a general method to ameliorate racism. This project might appear tone-deaf: a white philosopher unifying things by reducing ideas to some central notion. But this unity isn’t about reducing things but rather integrating them in a way that respects difference. Yet, there’s a reason we should be interested in the white perspective. Whites can speak about racism from a participatory perspective. If whites are knowledgeable, and believe themselves to have no implicit bias, they may suppose they’re “beyond” racism or no longer at risk for perpetuating it. I explore this idea in a psychologically realistic way via my notion of overlooking, where ameliorating racism from the white perspective is an ongoing project. I end by considering how racism is applicable to other philosophical ideas beyond its typical or circumscribed purview. Here, I re-frame responsibility, arguing that we needn’t be forced to choose between responsibility models divided into individual versus social camps. We ought to instead think of responsibility in terms of power, which provides a realistic lens by which persons and groups are held to account. In being more generally convincing, it might actually get folks to take responsibility where they might not otherwise—theory in service of praxis.