Neutropenia as a prognostic factor and safety of second-line therapy with S-1 for advanced or recurrent pancreatic cancer

Abstract

Abstract. The aim of this retrospective study was to investigate the safety of S-1 as second-line therapy and to evaluate the association between neutropenia occurring during first-line gemcitabine (GEM) therapy and survival for advanced or recurrent pancreatic cancer (APC). Between January, 2010 and December, 2014, 123 APC patients received chemotherapy at the Ogaki Municipal Hospital (Ogaki, Japan). Of those, 37 received GEM as first-line and S-1 as a second-line therapy (GEM→S-1 group). A further 60 patients received GEM as first-line therapy, but did not receive second-line therapy (GEM group). The median overall survival in the GEM→S-1 (n=37) and GEM (n=60) groups was 323 days [95% confidence interval (CI): 138-218.9 days] and 172 days (95% CI: 105-184.4 days), respectively (P=0.0004). The median overall survival in the mild (grade ≤2; n=63) and severe (grade ≥3; n=34) neutropenia groups was 178 days (95% CI: 182-275 days) and 330 days (95% CI: 297-514 days), respectively (log-rank test, P=0.0023). The severe non-haematological toxicities associated with S-1 as second-line therapy were nausea (2.7%) and hand-foot syndrome (2.7%). Second-line S-1 treatment was discontinued due to adverse events in 5.4% (2̸37) of the cases. In conclusion, neutropenia occurring during GEM therapy administered as first-line treatment to APC patients was strongly associated with a better prognosis. S-1 therapy as second-line treatment was associated with a low incidence of severe adverse events and the patients were able to successfully continue treatment.

Dose considerations for anti-cancer drugs in metastatic prostate cancer

“…With regards to cabazitaxel, a post‐hoc analysis of the TROPIC study showed an improvement in OS (16.3 months vs 14.0, HR 0.65, P = 0.035) and PFS (4.6 m vs 2.1 m, HR 0.56, P = 0.001) for patients with Grade ≥3 neutropenia compared to those with Grade <3 neutropenia . A similar association between lack of chemotherapy‐induced neutropenia and worse survival has been shown for many cancers such as Hodgkin's lymphoma, ovarian cancer, non‐small cell lung cancer, breast, gastric, pancreatic, colorectal, and testicular cancers …”

“…20 A similar association between lack of chemotherapy-induced neutropenia and worse survival has been shown for many cancers such as Hodgkin's lymphoma, ovarian cancer, non-small cell lung cancer, breast, gastric, pancreatic, colorectal, and testicular cancers. [21][22][23][24][25][26][27][28][29][30][31][32][33] The FIRSTANA and PROSELICA trials showed no difference in survival and progression-free survival between 25 and 20 mg/m 2 dosing for cabazitaxel though the toxicity profile was better with 20 mg/m 2 . 34,35 Thus, for a population of patients, a starting dose of 20 mg/m 2 can be recommended for cabazitaxel.…”

The maximum chemiluminescence intensity predicts severe neutropenia in gemcitabine-treated patients with pancreatic or biliary tract cancer

“…SN is associated with the long-term prognosis of patients with various types of cancer, including breast [ 31 , 32 ], small cell lung [ 33 , 34 ], gastric [ 35 ], colorectal [ 36 , 37 ], ovarian [ 38 ], and pancreatic [ 39 , 40 ]. The long-term prognosis may be associated with SN and CI max , though this was not evaluated in this study.…”

Development of new promising antimetabolite, DFP-11207 with self-controlled toxicity in rodents

“…Due to the nature of a cocktail formulation, each component in S-1 exhibits independent PK profile, respectively. Especially the higher C max level of 5-FU derived from tegafur in the blood resulted in hematological and/or GI toxicities in patients for a long-term use 15,20. Accordingly, it is desired to have 5-FU level in blood maintained for a long-time at a relatively low C max level for a new oral candidate of fluoropyrimidine derivatives.…”