After approval from the IRB (the ethics committee for biomedical research) in our university, a phase I study of adjuvant bi-weekly GEM chemotherapy was conducted in our institute using three different doses: a high dose (1,200 mg/m2), a medium dose (1,000 mg/m2), and a low dose (800 mg/m2). Each dose group consisted of at least six patients; the compliance rate in the high dose group was low, 47%, while the rates in the middle and low dose groups were 96% and 97%. Moreover, there was no significant difference in the side effects between the middle and low dose groups according to the common toxicity criteria of the ECOG. Consequently, the appropriate dose-intensity of adjuvant bi-weekly GEM chemotherapy was set at 1,000 mg/m2 in our institute. During a five-year period between 2004 and 2009, 128 patients with ductal pancreatic carcinomas were treated with surgery in our institution. A clinical study of mild dose-intensity, adjuvant bi-weekly GEM chemotherapy was performed with a total of 58 pancreatic cancer patients (Group A), who gave informed consent (IC). On the other hand, 36 patients (Group B), who did not give IC for adjuvant bi-weekly GEM chemotherapy, chose 5FU-based chemotherapy as the traditional adjuvant treatment. The remaining 34 patients were excluded from this study due to: macroscopic non-curative surgical treatment (22 cases), previous treatment of the current disease with more than one chemotherapeutic regimen and/or radiotherapy (3 cases), major complications after surgery such as aspiration pneumonia and/or leakage of pancreatojejunostomy (2 cases), hospital death after aggressive progression of the disease (1 case), not less than 85 years old (1 case), not providing IC for adjuvant chemotherapy (1 case), and physical conditions: active infection (1 case), interstitial pneumonia or pulmonary fibrosis (1 case), myocardial infarction within 3 months (1 case), and concomitant advanced cancer (1 case).
In Group A, the first administration of 1,000 mg/m2 of GEM was given during the third week after surgery, that is, 15–21 postoperative days (POD) if the patient’s condition was favorable. One cycle of this regimen was defined as twice bi-weekly administrations of GEM. After discharge from our hospital, administration of 1,000 mg/m2 of GEM was given consecutively to the outpatients at bi-weekly intervals, for at least six full cycles or until the patient’s condition was considered tolerable. If severe side effects occurred, the 1,000 mg/m2 dosage of GEM was reduced to 800 mg/m2. These severe side effects were: leukopenia <1,000 / mm-3, decreasing platelets <20,000 / mm-3, neutrophils <1,000 / mm-3 with fever (>38°C) or infection, and non-hematologic toxicity higher than Grade 3 according to the common toxicity criteria of the ECOG except for gastrointestinal toxicity, such as nausea, vomiting, diarrhea, and stomatitis. Additionally, when there were multiple side effects, the administration of GEM was extended until the patient’s recovery. If recovery needed more than two weeks, the study was discontinued. The multiple side effects were: leukopenia <2,000 / mm-3, decreasing platelets <70,000 / mm-3, and non-hematologic toxicity higher than Grade 2 according to the common toxicity criteria of the ECOG except for gastrointestinal toxicity, such as nausea, vomiting, diarrhea, and stomatitis.
In Group B, the postoperative patients were treated with adjuvant 5FU-based chemotherapy consisting of an intravenous 20 mg/m2 bolus of leucovorin followed by an intravenous 400 mg/m2 bolus of fluorouracil given on each 5 consecutive days every 28 days for 6 cycles. The adjuvant 5FU-based chemotherapy was also started during the third week after surgery, the same as Group A. When recurrence was identified in Group B, the adjuvant chemotherapy was converted from 5FU-based to standard GEM administration (1,000 mg/m2 on days 1, 8, and 15, repeated every four weeks for a total of at least six courses) as for the patients who had agreed with the therapy alteration.
The patients in both groups were followed up carefully, especially for side effects from the agents, disease recurrence, and the patients’ QOL, as measured according to the European Organisation for Research and Treatment of Cancer’s (EORTC) quality of life questionnaire (quality of life questionnaire – core 30 or QLQ-C30) and the pancreatic cancer-specific supplemental module (quality of life questionnaire – pancreatic cancer module 26 or QLQ-PAN26) [10–13]. The assessment of patients’ QOL in both groups was carried out at each outpatient appointment. Postoperative surveillance for the recurrence of pancreatic cancer was undertaken every three months.
Thus, the 58 cases in Group A were compared to the 36 cases in Group B retrospectively. Statistical analysis was performed using student’s t-test, the chi-square test, the Mann–Whitney test, the log-rank test, the Kaplan–Meier method, and the Cox hazard proportional model. Results were considered to be statistically significant when P < 0.05.