One of the observations that physicians often made when the standard of care treatment typically consisted of the chemotherapy drug agent of gemcitabine alone, was that many patients with pancreatic cancer (ductal adenocarcinoma of the pancreas) seemed to feel better after the initiation of treatment. In the past five years with the since widely deployed four-drug fluorouracil based regimen called FOLFIRINOX and with the introduction of the combination regimen of gemcitabine plus Abraxane for advanced pancreatic cancer, can this reassuring expressed attitude still be held as more or less true?
This is the question that Solheim, and his fellow Norwegian authors from the Trondheim University Hospital tried to address in a study published in the March 2016 issue of Critical Reviews in Oncology / Hematology. Winnowed down from 872 abstracts, they reviewed 36 published study-and-trial-results to examine whether the overall patient sense of well-being was improved or worsened by chemotherapy treatments in the face of advanced pancreatic cancer, and somewhat apart from the specific side-effects of drug regimens. They looked for reported changes in health-related quality of life (QOL) including especially pain, and cachexia (pathologic weight loss or wasting) from the start of treatment of the pancreatic cancer, and between treatment arms within the research studies. Sparse and inconsistent reporting by the original studies, as well as patient attrition, thwarted definitive conclusions. Nevertheless, the researchers uncovered some interesting results.
Fourteen of the studies of treatment effects on patients with advanced pancreatic cancer reported out changes in QOL of patients over time. Five of these fourteen studies (35%) showed improvements in QOL in at least one treatment arm. Three studies (21%) reported worsened QOL in at least one treatment arm. In seven studies (50%) QOL measures were noted as stable over time. The authors conclude that chemotherapy can stabilize and even improve QOL factors for patients with pancreatic cancer. The important caution here is that assessments were based on patients who remained in the studies – not the entire population. The majority of patients discontinued treatments presumably often due to toxicity or progression of their pancreatic cancer and were not assessed, making definitive conclusions problematic.
The authors also intentionally reviewed the effects of chemotherapy and that of pain related to pancreatic cancer. Most treatment arms utilizing chemotherapy reported patient improvement of pain, often measured by pain scales and/or by changes in analgesic dosage. Only two treatment arms (of eight total) reported worsened pain over time compared to that at the point of enrollment. The conclusion of improved pain control with chemotherapy in advanced pancreatic cancer was stronger than that of general QOL, especially for treatment regimens that improved overall survival.
Cachexia (physical wasting) was inadequately and typically not addressed by the studies. The authors were unable to draw any conclusions about the effect of chemotherapy in pancreatic cancer treatment in terms of cachexia due to differing definitions of weight gain, exclusion of patients losing weight, missing details, and other factors.
The researchers offered interesting observations about the FOLFIRINOX regimen alone, and in contrast to gemcitabine and gemcitabine combination therapy in the treatment of advanced pancreatic cancer, although there were no observations related to the use of the gemcitabine plus Abraxane regimen. They addressed a study on the effects of FOLFIRINOX whereby a number of QOL symptoms appeared to be improved by the chemotherapy including anorexia, insomnia, constipation, emotional functionality, and general health status. They noted in another study that the time until deterioration of pain status was significantly longer with FOLFIRINOX than in the study arm treated with gemcitabine alone.
In terms of gemcitabine and gemcitabine combination therapy for the treatment of pancreatic cancer, the authors cited a study whereby mood, sense of physical well-being, functional performance, and coping efforts were improved over time compared to that at the initiation of chemotherapy. They noted that in those of the seven (of total 24) studies that did pain assessment, gemcitabine appeared to be related to a 50% reduction in pain or a reduction in analgesics in about a quarter of patients compared to about 5% of those receiving fluorouracil.
This somewhat rare look at patient quality of life issues in advanced pancreatic cancer was hindered by incomplete and inconsistent reporting from the studies in question. But, it appears that stabilization of health-related quality of life and improved pain control tended to be shown in the patient populations who remained under chemotherapy treatment. And the authors also found that quality of life improvements during therapy tended to be more strongly correlated with the more effective treatment regimens.
This is an engaging view with a somewhat reassuring albeit tentative conclusion. Chemotherapy with all of if its side effects can provide a possible upside in quality of life measures in advanced pancreatic cancer. It may be difficult, but we wonder if future studies might additionally consider creative means of trying to capture quality assessments of patients who are forced to leave treatment. And it will be interesting to see where the gemcitabine plus Abraxane regimen fits into this provisional understanding.
David Dessert