Bulls contend that FOLFIRINOX is too toxic for most patients to tolerate. I'm not so sure that's true, and physician opinions vary. Importantly, despite the increased toxicity, FOLFIRINOX-treated patients in the NEJM study had a significantly longer "time to deterioration," as measured by quality of life scores, than did those in the gemcitabine arm. Meanwhile, Threshold's investigators have noted that low dose TH-302 recipients demonstrate improved dose intensity -- a measure of tolerability -- than those treated with higher doses. Those factors indicate that TH-302 isn't devoid of meaningful adverse effects, and suggest that FOLFIRINOX may be less toxic than feared. The NEJM study results also appear to be reproducible. A study published earlier this month (Peddi et al. J Pancreas 2012 Sep 10; 13(5):497-501) by investigators from the Mayo Clinic, Washington University, and University of Wisconsin demonstrates even better outcomes for PFS (7.5 months) and overall survival (13.5 months) with FOLFIRINOX. Admittedly, this is a single-arm trial in relatively very healthy individuals, but the investigators conclusion is noteworthy: "FOLFIRINOX...is more effective than any other regimen in patients with pancreatic cancer and its toxicities did not preclude its use in the patients studied in this review." Threshold's pivotal phase III trial, which is still being planned, will compare TH-302 against FOLFIRINOX and increase the risk of failure, or against gemcitabine and risk irrelevance. I'm assuming the latter. In that case, TH-302 may prove modestly effective compared to gemcitabine, but it won't reach the market for at least three years. Further, I'm not sure how Threshold and partner Merck KGaA intend to differentiate TH-302 and justify branded pricing, especially given that inexpensive generic alternatives like FOLFIRINOX seem to have superior efficacy. Lastly, several competitors will report pivotal trial data for novel agents in pancreatic cancer over the next six months, most notably Celgene's ( CELG) Abraxane and Clovis Oncology's ( CLVS) CO-101. Should any of those drugs show a meaningful benefit, the bull case on Threshold will be even harder to make. For more on Threshold, read columnist Adam Feuerstein's view of the TH-302 pancreatic cancer data. Sadeghi has no position in any stocks mentioned in this column. Follow Nathan Sadeghi-Nejad on Twitter.