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Articles by F Fang
Total Records ( 4 ) for F Fang
  S Goel , A. C Mita , M Mita , E. K Rowinsky , Q. S Chu , N Wong , C Desjardins , F Fang , M Jansen , D. E Shuster , S Mani and C. H. Takimoto

Purpose: Eribulin mesylate (E7389), a non-taxane microtubule dynamics inhibitor, is a structurally simplified, synthetic analogue of halichondrin B that acts via a mechanism distinct from conventional tubulin-targeted agents. This phase I study determined the maximum tolerated dose (MTD) and pharmacokinetics of eribulin administered on a 3 of 4 week schedule in patients with advanced solid malignancies.

Experimental Design: Patients received eribulin mesylate (1-hour i.v. infusion) on days 1, 8, and 15 of a 28-day cycle. Dosing began at 0.25 mg/m2 with escalation guided by dose-limiting toxicities (DLT). MTD, DLTs, safety, pharmacokinetics, and antitumor activity were characterized.

Results: Thirty-two patients received eribulin mesylate (0.25, 0.5, 0.7, 1.0, or 1.4 mg/m2). Neutropenia was the principal DLT: At 1.4 mg/m2, two patients experienced grade 4 neutropenia, one of whom also developed grade 3 fatigue; three additional patients experienced grade 3 neutropenia and were not treated during cycle 1 on day 15. Therefore, the MTD was 1.0 mg/m2. Fatigue (53% overall, 13% grade 3, no grade 4), nausea (41%, all grade 1/2), and anorexia (38% overall, 3% grade 3, no grade 4) were the most common eribulin-related adverse events. Eight patients reported grade 1/2 neuropathy (no grade 3/4). Eribulin pharmacokinetics were dose-proportional over the dose range studied. One patient (cervical cancer) achieved an unconfirmed partial response lasting 79 days. Ten patients reported stable disease.

Conclusions: Eribulin mesylate, given on days 1, 8, and 15 of a 28-day cycle, exhibits manageable tolerability at 1.0 mg/m2 with further dose escalation limited by neutropenia and fatigue.

  A. R Tan , E. H Rubin , D. C Walton , D. E Shuster , Y. N Wong , F Fang , S Ashworth and L. S. Rosen

Purpose: To evaluate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of eribulin mesylate (E7389), a halichondrin B analogue, administered every 21 days in patients with advanced solid tumors.

Experimental Design: Eribulin mesylate was given as a 1-hour infusion every 21 days at doses of 0.25, 0.5, 1, 2, 2.8, and 4 mg/m2. The MTD was identified using an accelerated titration design. The pharmacokinetics of eribulin were evaluated in the plasma and urine with the first dose.

Results: Twenty-one patients were enrolled. At 4 mg/m2, three patients experienced a DLT of febrile neutropenia on day 7. The dose level was reduced to 2.8 mg/m2 where two of three patients experienced dose-limiting febrile neutropenia. Six additional patients were enrolled at 2 mg/m2 (seven patients in total received this dose) and one of these patients experienced a neutropenic DLT. The MTD of eribulin mesylate was therefore 2 mg/m2. Nonhematologic toxicities included alopecia, fatigue, anorexia, and nausea. Pharmacokinetic analysis showed linear kinetics for eribulin over the dose range studied and a terminal half-life of 2 days. The plasma-concentration-time profile exhibited a rapid distribution phase followed by a slow elimination phase. Drug clearance was nonrenal. One patient with non–small cell lung cancer achieved an unconfirmed partial response and 12 patients had stable disease.

Conclusions: Eribulin mesylate administered as a 1-hour infusion every 21 days has a manageable toxicity profile at 2 mg/m2, with further dose escalation limited by neutropenia.

  F Fang , N. L Keating , L. A Mucci , H. O Adami , M. J Stampfer , U Valdimarsdottir and K. Fall

Receiving a cancer diagnosis is a stressful event that may increase risks of suicide and cardiovascular death, especially soon after diagnosis.


We conducted a cohort study of 342 497 patients diagnosed with prostate cancer from January 1, 1979, through December 31, 2004, in the Surveillance, Epidemiology, and End Results Program. Follow-up started from the date of prostate cancer diagnosis to the end of first 12 calendar months after diagnosis. The relative risks of suicide and cardiovascular death were calculated as standardized mortality ratios (SMRs) comparing corresponding incidences among prostate cancer patients with those of the general US male population, with adjustment for age, calendar period, and state of residence. We compared risks in the first year and months after a prostate cancer diagnosis. The analyses were further stratified by calendar period at diagnosis, tumor characteristics, and other variables.


During follow-up, 148 men died of suicide (mortality rate = 0.5 per 1000 person-years) and 6845 died of cardiovascular diseases (mortality rate = 21.8 per 1000 person-years). Patients with prostate cancer were at increased risk of suicide during the first year (SMR = 1.4, 95% confidence interval [CI] = 1.2 to 1.6), especially during the first 3 months (SMR = 1.9, 95% CI = 1.4 to 2.6), after diagnosis. The elevated risk was apparent in pre–prostate-specific antigen (PSA) (1979–1986) and peri–PSA (1987–1992) eras but not since PSA testing has been widespread (1993–2004). The risk of cardiovascular death was slightly elevated during the first year (SMR = 1.09, 95% CI = 1.06 to 1.12), with the highest risk in the first month (SMR = 2.05, 95% CI = 1.89 to 2.22), after diagnosis. The first-month risk was statistically significantly elevated during the entire study period, and the risk was higher for patients with metastatic tumors (SMR = 3.22, 95% CI = 2.68 to 3.84) than for those with local or regional tumors (SMR = 1.57, 95% CI = 1.42 to 1.74).


A diagnosis of prostate cancer may increase the immediate risks of suicide and cardiovascular death.

  K. M Roth , J Byam , F Fang and J. S. Butler

The nuclear exosome functions in a variety of pathways catalyzing formation of mature RNA 3'-ends or the destruction of aberrant RNA transcripts. The RNA 3'-end formation activity of the exosome appeared restricted to small noncoding RNAs. However, the nuclear exosome controls the level of the mRNA encoding the poly(A)-binding protein Nab2p in a manner requiring an A26 sequence in the mRNA 3' untranslated regions (UTR), and the activities of Nab2p and the exosome-associated exoribonuclease Rrp6p. Here we show that the A26 sequence inhibits normal 3'-end processing of NAB2 mRNA in vivo and in vitro, and makes formation of the mature 3'-end dependent on trimming of the transcript by the core exosome and the Trf4p component of the TRAMP complex from a downstream site. The detection of mature, polyadenylated transcripts ending at, or within, the A26 sequence indicates that exosome trimming sometimes gives way to polyadenylation of the mRNA. Alternatively, Rrp6p and the TRAMP-associated Mtr4p degrade these transcripts thereby limiting the amount of Nab2p in the cell. These findings suggest that NAB2 mRNA 3'-end formation requires the exosome and TRAMP complex, and that competition between polyadenylation and Rrp6p-dependent degradation controls the level of this mRNA.

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