Gemcitabine and lenalidomide combination in a patient with metastatic pancreatic cancer: a case study
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- Liu, W.M., Nizar, S. & Dalgleish, A.G. Med Oncol (2010) 27: 430. doi:10.1007/s12032-009-9228-6
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The proportion of people surviving pancreatic cancer is extremely low, with just 10% of patients diagnosed with any stage of the disease living beyond 1 year and a 5-year relative survival rate of <5%. The lack of effective therapy is one the main reason for such a bleak outlook. Herein, we report on a patient with pancreatic adenocarcinoma and metastatic disease treated with a combination regimen of gemcitabine and lenalidomide, without major complications. We also present in vitro data that highlight a hyper-additive effect of the two drugs when used in combination. To date, 33 months after diagnosis, the patient remains well and continues in full-time employment.
KeywordsPancreatic cancerDrug combination therapyGemcitabineLenalidomide
Current statistics place pancreatic cancer as the fourth most common cause of cancer related death in the world today, after lung, colon and breast . This cancer is remarkable in that it has a death rate that almost equals the incidence rate . The proportion of people surviving pancreatic cancer is extremely low, with just 10% of patients diagnosed with any stage of the disease living beyond 1 year, and a 5-year relative survival rate of <5% [1–3]. In addition to difficulties in diagnosis, one reason for the high mortality associated with pancreatic cancer is a lack of effective therapy, as the disease possesses multiple molecular aberrations that result in the disease being intrinsically resistant to chemotherapy . The optimum treatment for pancreatic disease has not been fully established, which currently involves modulation of disease using gemcitabine. However, although it is the leading treatment, it only offers modest survival benefits, and the survival rate at 12 months is just 18% [5, 6]. Here, we report on a patient with pancreatic adenocarcinoma and metastatic disease treated with a combination regimen of gemcitabine and lenalidomide, without major complications, and compared the response with a crude in vitro model of drug combination.
Currently, the standard treatment for patients with pancreatic cancer is gemcitabine. It produces significant improvements to treatment strategies compared to the previous gold standard of treatment in 5-flurouracil. However, although gemcitabine is the leading treatment, it only offers modest survival benefits, and the survival rate at 12 months is just 18% .
Combinational therapeutic approaches have shown great benefit, and indeed, have been shown to singly enhance the efficacy of novel agents, which alone have minimal effect . In particular, combination approaches with gemcitabine and chemotherapy such as irinotecan, capecitabine and gefitinib have proved successful, , and studies have reported small improvements and prolongation of life; however, they have been associated with marked increase in toxicities.
At the commencement of administration in this patient, there were no reports of combinations with gemcitabine and lenalidomide. Reasons for potential synergy were considered to be indirect effects such as enhancement of immunological responses, as well as direct ones (e.g. suppression of angiogenesis). More importantly, an accumulation of myeloid suppressive T-cells has been attributed to decreased immune function in patients through inhibition of antigen-presenting functionality [9, 10]. It has thus been suggested that elimination of these myeloid suppressor cells, which is possible through the administration of gemcitabine , may improve the effects of cancer immunotherapies such as those related to thalidomide [7, 12].
The use of gemcitabine with lenalidomide reported here that lead to dramatic falls in a marker for pancreatic cancer and disease stabilisation is further highlighted when the patient had to be taken off treatment when unwell. In particular, during the last quarter of 2008, the patient developed a pulmonary infection that brought about a suspension of medication. Her CA 19-9 rose during this break, which on resumption of treatment, started to fall again. Interestingly, the disease management became similar to that of a chronic nature in that rather than using chemotherapy as a way of induction remission, it is now used to maintain a stable-disease state and in doing so, extend life.
In conclusion, we describe a patient with metastatic pancreatic cancer who would not have been expected to survive more than 6 months, but has now survived over 33-months. Her disease management was a combination of gemcitabine and lenalidomide, neither of which can be stopped without biochemical and clinical deterioration.