Adjuvant Chemotherapy Of S-1 Versus Gemcitabine For Resected Pancreatic Cancer

A new study has been published in The Lancet on 2nd June, 2016, that claims that the S-1 drug is more effective than the gold standard in improving the survival and quality of life in patients with resected pancreatic cancer — gemcitabine therapy.

The drug was studied among the Japanese population. Confident with the findings, the researchers have proposed that the results be verified in non-Asian populations also.

The aim of the study was to check whether the S-1 drug, as a form of adjuvant chemotherapy, reduced risks of recurring pancreatic cancer and ensured survival and quality of life among the subjects during follow-up years.


The study was conducted by Japan Adjuvant Study Group of Pancreatic Cancer (JASPAC) in 33 different hospitals (13 university hospitals, 10 cancer center hospitals and 10 general hospitals) in Japan from April 11th, 2007-June 29th, 2010. Participants were aware of the procedure, type and doses of the prescribed medication.

The entire study was funded by the Japanese national social insurance system. The selection criteria of the study required patients to have a histologically proven invasive ductal carcinoma of the pancreas. Patients were also required to not have a previous three-year history of chemotherapy and radiotherapy along with having appropriate liver and kidney functioning. An adequate amount of bone marrow measurement taken seven days before the registration was also required.

Additionally, participants aged 20 years or older with a maximum capacity of taking oral medicines were picked. All participants were demanded to provide a written informed consent as well. Two groups were made — with patients being randomly assigned to either the gemcitabine group or the S-1 group.

Out of the total 385 patients enrolled in the study, 193 were assigned to the gemcitabine group and 192 were allocated to the S-1 group. After inclusion and exclusion, a total of 190 patients were left in the gemcitabine group while 187 were left in the S-1 group. These patients constituted the pre-protocol population.

Outcomes And Results

This open-label study demonstrated the fact that adjuvant chemotherapy with the S-1 drug was associated with a higher 5-year survival rate in the S-1 group than the others. The actual HR in this whole trial was 0.57 which not only showed the non-inferiority but the superiority of S-1 over gemcitabine. Hence, it was concluded that postoperative treatment with S-1 significantly increases the overall or relapse-free survival of Japanese patients with resected pancreatic cancer.

Possibilities Supporting The Outcomes

One possible reason for the low mortality rate with postoperative S-1 adjuvant chemotherapy could be the higher response of the S-1 compared to the gemcitabine in the GEST study. The second possibility was expected to be the continuous dosage of the S-1 drug for 28 days.

Additionally, a high tolerance of the S-1 drug after pancreatic resection has also been observed which ultimately supported the findings. However, these reasons are still insufficient to explain the efficacy of S-1 associated with a low mortality rate in patients with resected pancreatic cancer.

Furthermore, Sakuramoto et al. also reported the use of S-1 drug in patients who had undergone D2 dissection for stage 2 and stage 3 gastric cancers. Therefore, it is said that S-1 along with some other drugs can be proven efficacious in adjuvant chemotherapies. However, further investigations are required to support the findings.

Limitations Of The Study

One of the limitations of this study was that the patients enrolled were all East Asian residents of Japan. It is recounted that pharmacokinetics and pharmacodynamics of the S-1 drug might exhibit differently in European and North American patients from those of patients from East Asia.

Supporting this fact, the grade 3 and 4 gastrointestinal toxicities were more prevalent among Europeans and North Americans than the East Asians. Accordingly, the Europeans and North Americans were dosed 30mg/m² twice a day for 28 days, which was actually lower than the dose the Japanese subjects received.

Another limitation was that the S-1 drug was only tested for its superiority in the pre-protocol population if non-inferiority was already confirmed in the pre-protocol population.

Gemcitabine Therapy For Pancreatic Cancer

Adjuvant chemotherapy is a preventive measure against the recurrence of any tumor being removed from the body. This is done to kill the probability of the cancer reappearing.

According to a study conducted in 2013, gemcitabine, tested as adjuvant chemotherapy for resected pancreatic cancer, maximized the overall or disease-free survival rate.

Additionally, Oettle et al. reported the long term effects of the CONKO-001 trial and demonstrated that the survival rate with gemcitabine treatment was higher than the observational group.

Since then, gemcitabine has successfully proven to be stable in postoperative adjuvant chemotherapy treatments. Although the new findings are astonishing, scientists claim more investigation is needed to support the findings.

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