Gemcitabine: Best Alone or in Combination?

Gemcitabine (GEM) is the standard treatment for patients with locally advanced/metastatic pancreatic cancer (LA/MPC). Many studies have focused on finding combinations that might extend the efficacy of GEM. However, most studies have not found an improvement in overall survival (OS) for patients using GEM combination therapy, say researchers from Beijing Friendship Hospital in China. That is until recently, when researchers found that compared with GEM monotherapy, nanoparticle albumin-bound paclitaxel plus GEM significantly improved OS (8.5 months vs 6.7 months; P < .001) and progression-free survival (5.5 months vs 3.7 months; P < .001).

Other research has found that combining GEM with platinum, fluoropyrimidine, irinotecan, biotherapy, and others, for example, marginally but significantly affects OS, again compared with GEM monotherapy (P = .001). The combinations were associated with increased toxicity.

According to the researchers, the use of targeted therapies in cancer treatment is a “significant focus” of cancer research and has brought great clinical benefits in treating a variety of solid tumors. Studies that combined drugs to target epidermal growth factor receptor (EGFR), which is overexpressed in pancreatic tumors and associated with poor prognosis, had mixed results for patients with LA/MPC. This prompted researchers in this study to conduct a systematic survey of 10 randomized controlled trials: 3 phase 2 trials and 7 phase 3 trials. Of 3,899 patients, 1,989 received GEM + targeted agents and 1,910 received GEM as monotherapy or combined with placebo (PLC).  In a subgroup of GEM + antiangiogenic agents, 733 patients received GEM + axitinib or bevacizumab and cilengitide, and 693 received GEM ± PLC.

No significant difference was seen in the OS rate between the GEM + targeted agents and GEM ± PLC groups (P = .85), and only a marginal difference was found in the 1-year survival rate (P = .05). In the subgroup analysis, the researchers found a significant increase in objective response rate with GEM + antiangiogenic agents vs GEM ± PLC (95% CI, 0.42-0.98; P = .04). However, they found no significant difference in OS, 1-year survival, or progression-free survival between those 2 groups.

The researchers advise further research concentrated on clarifying the “concrete targets” involved in the occurrence and progression of pancreatic cancer. They add that personalized therapy based on a patient’s stratification, tumor stage, and genetic background should also be considered.

Source
Li Q, Yuan Z, Yan H, Wen Z, Zhang R, Cao B. Clin Ther. 2014;36(7):1054-1063.
doi: 10.1016/j.clinthera.2014.05.066.

Gemcitabine (GEM) is the standard treatment for patients with locally advanced/metastatic pancreatic cancer (LA/MPC). Many studies have focused on finding combinations that might extend the efficacy of GEM. However, most studies have not found an improvement in overall survival (OS) for patients using GEM combination therapy, say researchers from Beijing Friendship Hospital in China. That is until recently, when researchers found that compared with GEM monotherapy, nanoparticle albumin-bound paclitaxel plus GEM significantly improved OS (8.5 months vs 6.7 months; P < .001) and progression-free survival (5.5 months vs 3.7 months; P < .001).

Other research has found that combining GEM with platinum, fluoropyrimidine, irinotecan, biotherapy, and others, for example, marginally but significantly affects OS, again compared with GEM monotherapy (P = .001). The combinations were associated with increased toxicity.

According to the researchers, the use of targeted therapies in cancer treatment is a “significant focus” of cancer research and has brought great clinical benefits in treating a variety of solid tumors. Studies that combined drugs to target epidermal growth factor receptor (EGFR), which is overexpressed in pancreatic tumors and associated with poor prognosis, had mixed results for patients with LA/MPC. This prompted researchers in this study to conduct a systematic survey of 10 randomized controlled trials: 3 phase 2 trials and 7 phase 3 trials. Of 3,899 patients, 1,989 received GEM + targeted agents and 1,910 received GEM as monotherapy or combined with placebo (PLC).  In a subgroup of GEM + antiangiogenic agents, 733 patients received GEM + axitinib or bevacizumab and cilengitide, and 693 received GEM ± PLC.

No significant difference was seen in the OS rate between the GEM + targeted agents and GEM ± PLC groups (P = .85), and only a marginal difference was found in the 1-year survival rate (P = .05). In the subgroup analysis, the researchers found a significant increase in objective response rate with GEM + antiangiogenic agents vs GEM ± PLC (95% CI, 0.42-0.98; P = .04). However, they found no significant difference in OS, 1-year survival, or progression-free survival between those 2 groups.

The researchers advise further research concentrated on clarifying the “concrete targets” involved in the occurrence and progression of pancreatic cancer. They add that personalized therapy based on a patient’s stratification, tumor stage, and genetic background should also be considered.

Source
Li Q, Yuan Z, Yan H, Wen Z, Zhang R, Cao B. Clin Ther. 2014;36(7):1054-1063.
doi: 10.1016/j.clinthera.2014.05.066.

Gemcitabine (GEM) is the standard treatment for patients with locally advanced/metastatic pancreatic cancer (LA/MPC). Many studies have focused on finding combinations that might extend the efficacy of GEM. However, most studies have not found an improvement in overall survival (OS) for patients using GEM combination therapy, say researchers from Beijing Friendship Hospital in China. That is until recently, when researchers found that compared with GEM monotherapy, nanoparticle albumin-bound paclitaxel plus GEM significantly improved OS (8.5 months vs 6.7 months; P < .001) and progression-free survival (5.5 months vs 3.7 months; P < .001).

Other research has found that combining GEM with platinum, fluoropyrimidine, irinotecan, biotherapy, and others, for example, marginally but significantly affects OS, again compared with GEM monotherapy (P = .001). The combinations were associated with increased toxicity.

According to the researchers, the use of targeted therapies in cancer treatment is a “significant focus” of cancer research and has brought great clinical benefits in treating a variety of solid tumors. Studies that combined drugs to target epidermal growth factor receptor (EGFR), which is overexpressed in pancreatic tumors and associated with poor prognosis, had mixed results for patients with LA/MPC. This prompted researchers in this study to conduct a systematic survey of 10 randomized controlled trials: 3 phase 2 trials and 7 phase 3 trials. Of 3,899 patients, 1,989 received GEM + targeted agents and 1,910 received GEM as monotherapy or combined with placebo (PLC).  In a subgroup of GEM + antiangiogenic agents, 733 patients received GEM + axitinib or bevacizumab and cilengitide, and 693 received GEM ± PLC.

No significant difference was seen in the OS rate between the GEM + targeted agents and GEM ± PLC groups (P = .85), and only a marginal difference was found in the 1-year survival rate (P = .05). In the subgroup analysis, the researchers found a significant increase in objective response rate with GEM + antiangiogenic agents vs GEM ± PLC (95% CI, 0.42-0.98; P = .04). However, they found no significant difference in OS, 1-year survival, or progression-free survival between those 2 groups.

The researchers advise further research concentrated on clarifying the “concrete targets” involved in the occurrence and progression of pancreatic cancer. They add that personalized therapy based on a patient’s stratification, tumor stage, and genetic background should also be considered.

Source
Li Q, Yuan Z, Yan H, Wen Z, Zhang R, Cao B. Clin Ther. 2014;36(7):1054-1063.
doi: 10.1016/j.clinthera.2014.05.066.