Background: Pancreatic ductal adenocarcinoma (PDAC) is most prevalent in elderly patients, with a median age of 70 years at the time of diagnosis. To our knowledge, there are no trials designed to evaluate the safety and efficacy of treatment for elderly patients with PDAC. The standard of care for PDAC employs the “maximum tolerated doses” of multidrug chemotherapy regimens. These regimens require extended rest periods from chemotherapy, enabling the regrowth of tumor cells and permitting the cancer stem cells to repopulate, which results in acquired chemoresistance. In contrast, “metronomic chemotherapy” is the frequent administration of lower doses of chemotherapy, without extended rest periods, hypothesized to limit the mechanisms driving acquired chemoresistance. Methods: Here, we report on our clinical experience using various metronomic chemotherapy regimens for 115 patients. Patients were 65 years of age or older with Stage III or IV PDAC. The most frequently employed regimens included prolonged 14-21-day infusions of 5- fluorouracil given in conjunction with at least two additional drugs, including gemcitabine, nab-paclitaxel and/or cisplatin, often depending on chemosensitivity assays. Results: The median duration of treatment was 12 months (range 1-208 months). Ninety-three patients (81%) lived 12 months or longer with a median overall survival of 24.6 months (range 1- 240+ months). Eight patients achieved a complete response and forty patients had a partial response. The overall response rate was 42%. Thirteen patients are alive, eight of whom are in sustained remission. Survival rates generally showed an inverse relationship with age. Overall, the metronomic multidrug regimens were well tolerated; the most common Grade 3 or4 treatment related adverse events include neutropenia (14%), febrile neutropenia (1%), thrombocytopenia (17%), anemia (20%), anorexia (22%), fatigue (31%), vomiting (6%), diarrhea (13%), neuropathy (8%), stomatitis (12%), hypertension (17%), pulmonary fibrosis (8%), and hemolytic uremic syndrome (3%). There were two drug-related deaths, including one patient diagnosed with acute leukemia, and one patient who developed multiple liver abscesses and sepsis secondary to cholangitis. Conclusions: Taken together, these data indicate that the use of metronomic chemotherapy is associated with (1) improved overall response and remission rates (2) less systemic toxicity, (3) improved quality of life in elderly patients with pancreatic ductal adenocarcinoma, and therefore is a better approach for this population with PDAC.
Isacoff et al. (Wed,) studied this question.