Of 70 patients with pancreatic cancer who expressed interest in the study, 15 patients were excluded (); nine did not meet the trial inclusion criteria; and one additional patient signed a consent form that was misplaced because of a change in staffing. Five additional patients had a delay in enrollment of greater than 8 weeks from the date of diagnosis and, thus, were ineligible. Several of these subjects were originally treated as part of the trial due to extenuating circumstances at the time of evaluation resulting in excessive elapsed time between diagnosis and therapy. Subjects often traveled great distances to be considered for this trial, and on several occasions, obtaining data at long distance or the requirement for subject travel (eg, travel to New York around the time of September 11, 2001) resulted in excessive delay. Data from these subjects are not included in the data reported in this article, in order that the analysis apply to subjects that strictly meet the inclusion criteria.
tudy design of controlled, nonrandomized trial. ECOG, Eastern Cooperative Oncology Group; BUN, blood urea nitrogen; SGOT, aspartate aminotransferase; SGPT, alanine aminotransferase.
On October 17, 2005, the stopping rule criterion was met, and the study was closed to accrual. Fifty-five patients, 23 on the control arm and 32 on the experimental arm, enrolled on the study and were available for analysis.
presents the demographic and clinical characteristics of the participating patients by treatment group. The patients in both the control and experimental arms were carefully enrolled according to identical entry criteria. There were no statistically significant differences at the time of enrollment in age, sex, weight, ECOG performance status, stage of disease, pathology, quality of life, or CA19-9. Bilirubin and albumen were significantly higher in the chemotherapy group, but all values were clinically within normal limits and met eligibility criteria.
Demographic and Clinical Characteristics of Patients in the Chemotherapy and Enzyme-Treatment Groups
The primary end point was overall survival. As the Kaplan-Meier curves demonstrate (), there was a 9.7-month median survival advantage for patients on chemotherapy treatment (median survival, 14 months) compared with those on enzyme treatment (median survival, 4.3 months; P < .001). The accompanying SEER (Surveillance, Epidemiology, and End Results) survival curve in has the same distribution of local and regional disease as the study population.
Kaplan-Meier curves for the enzyme and chemotherapy (chemo) groups and for patients with stages II to IV pancreatic cancer in SEER (Surveillance, Epidemiology, and End Results).
Twelve months after enrollment, 56% of chemotherapy-group patients were alive; 16% of the enzyme-group patients were alive. The longest survivors were one chemotherapy-group patient who died at 39.5 months and one chemotherapy-group patient who was censored at 37.5 months (ie, the closing date of the data analysis) and, at the time of manuscript submission, was still alive at 40 months.
Both propensity score–adjusted and multivariate Cox proportional hazards models were used to estimate the relative risk for mortality. The log-rank test for analyzing the group effect on survival times adjusted by propensity scores was less than .001. Both methods gave similar results ().
Adverse events appeared similar in both groups and were difficult to distinguish from the morbidity of progressive pancreatic cancer. One patient in the chemotherapy group died as a result of a pulmonary embolus.
Patients in the two groups responded similarly to the questionnaires on quality of life before initiation of therapy, but the overall FACT-PA scores during 12 months decreased more in the enzyme group than in the gemcitabine group (). Twenty-four percent of total measurements were missing. Quality of life scores of both groups were significantly different (P < .01). During the first 6 months of the study, pain scores increased in the enzyme group, but they decreased in the chemotherapy group (P < .05); however, few patients reported on use of analgesics. ().
Mean Functional Assessment of Cancer questionnaire for pancreatic cancer (FACT-PA; ie, quality of life) scores of the chemotherapy (chemo) group and the enzyme-therapy group in the first year of the study.