The efficacy of such agents in pancreas cancer is to be evaluated (78). Cytotoxics Gemcitabine has been the chemotherapy backbone for the treatment of
newly diagnosed advanced pancreas cancer (79),(80). Various other cytotoxic drugs had been tested in combination with gemcitabine, including fluoropyrimidines, platinum derivatives, and taxanes (80)-(84). Meta-analysis of various cytotoxic trials over the last one-and-a-half decades suggest improved survival with doublet or triplet gemcitabine-based therapy among patients with good performance status, who can, supposedly, better withstand the toxicities (85). Final results from the interim analysis of the PRODIDGE 4/ACCORD Inhibitors,research,lifescience,medical 11 trial were presented at 2010 European Society for Medical Oncology annual meeting, which randomized 342 patients with previously untreated
metastatic pancreas cancer to Ipatasertib clinical trial receiving FOLFIRINOX (oxaliplatin 85 mg/m(2) Day 1 + irinotecan 180 mg/m(2) Day 1 + leucovorin 400 mg/m(2) Day 1 followed by 5-flurouracil 400 mg/m(2) bolus Day 1 and 2,400 mg/m(2) 46 hours continuous infusion biweekly) Inhibitors,research,lifescience,medical or gemcitabine alone. The study was stopped on recommendation by the independent monitoring committee during preplanned interim analysis when FOLFIRINIOX was determined Inhibitors,research,lifescience,medical to be superior to gemcitabine alone, making the fluoropyrimidine-based regimen first non-gemcitabine based regimen to show significant improvement in overall survival. The objective response rate for FOLFIRINOX, compared to gemcitabine alone, was 31.6% vs 9.4% (P=0.0001), median PFS 6.4 vs 3.3 months (P<0.0001) and median survival 11.1 vs 6.8 months (HR=0.57, 95% CI Inhibitors,research,lifescience,medical =0.45-0.73;
P<0.001) respectively. However, there were significantly more grade 3 and above toxicities in the FOLFIRINOX arm, including diarrhea, nausea, vomiting, neuropathy, neutropenia, Inhibitors,research,lifescience,medical neutropenic fever. Given the higher frequency of clinically significant toxicities, FOLFIRINOX cannot be accepted as the standard first-line treatment for all newly diagnosed advanced pancreas cancer patients. The choice of FOLFIRINOX in advanced patients needs to be personalized according to factors such as performance status, treatment aim, physiological reserve and patient preference, and the role in adjuvant setting is being evaluated. Nab-paclitaxel (Abraxane®; Abraxis) is a nano-particle preparation in which paclitaxel is bound to albumin as compared many to sb-paclitaxel (Taxol®, Bristol Meyers Squibb), which is dissolved in poloxyethylated castor oil (Cremaphor EL®) and ethanol. The absence of castor oil renders nab-paclitaxel clinically advantageous since this avoids the infusion and hypersensitivity reaction characteristics of sb-paclitaxel. In the initial phase I clinical trial of nab-paclitaxel, there was no hypersensitivity reaction typical of sb-paclitaxel and was well tolerated up to 300mg/m2 administered as a 30-minute infusion (86).