clinical topic updates

Modifying Treatment Regimens to Attenuate Toxicity in Metastatic Pancreatic Cancer

by Philip A. Philip, MD, PhD, FRCP

Overview

Newly approved chemotherapy regimens in the treatment of metastatic pancreatic cancer, such as FOLFIRINOX* and gemcitabine-nab-paclitaxel, have increased efficacy but also toxicity. Despite various modified FOLFIRINOX treatment regimens, how much modification and dose reduction is acceptable to maintain efficacy remains unclear from clinical studies. A member of our expert panel explains if treatment toxicity can be attenuated with dose reduction in clinical practice.

Expert Commentary

Philip A. Philip, MD, PhD, FRCP

Professor of Oncology and Internal Medicine
Vice President for Medical Affairs
Barbara Ann Karmanos Cancer Institute
Wayne State University School of Medicine
Detroit, MI

Is there a way that we can start with a lower dose of the regimen or lower the dose in patients who experience side effects? With FOLFIRINOX, in the United States, I would say a lot of people would start the treatment without the bolus 5-fluorouracil (5-FU). Trying to not use bolus 5-FU is considered to be one way of trying to give the treatment with a lesser chance of having some of the hematologic side effects, and also the gastrointestinal (GI) toxicities. However, different clinicians will also adopt different ways of trying to modify FOLFIRINOX treatment. For example, some people will start the FOLFIRINOX treatment with 20% dose reductions across the board. With gemcitabine + nab-paclitaxel, when we are trying to handle toxicity, one way is to try to give it every 2 weeks. You can either give it the usual way, which is 3 weeks on and 1 week off, but you can also give it every other week. In my practice and my experience, with patients who are older and may have borderline performance status, I sometimes start with every other week of treatment. In some of those patients, I might even start with every other week and a 20% dose reduction of both drugs. In patients who have informal toxicity on gemcitabine + nab-paclitaxel, I may also switch it up, providing a better chance for the patient to recover from the side effects between treatment. These are some things that clinicians can do. You can either start with a modified treatment regimen or modify the regimen as the patient develops side effects.

“You can either start with a modified treatment regimen or modify the regimen as the patient develops side effects.”

Philip A. Philip, MD, PhD, FRCP

*FOLFIRINOX: FOL=leucovorin calcium (folinic acid); F=5-fluorouracil; IRIN=irinotecan hydrochloride; OX=oxaliplatin.

References

Lee JC, Kim JW, Ahn S, Kim HW, Lee J, Kim YH, et al. Optimal dose reduction of FOLFIRINOX for preserving tumour response in advanced pancreatic cancer: Using cumulative relative dose intensity. Eur J Cancer. 2017;76:125-133.

Liu GF, Li GJ, Zhao H. Efficacy and toxicity of different chemotherapy regimens in the treatment of advanced or metastatic pancreatic cancer: a network meta-analysis. J Cell Biochem. June 13, 2017. doi: 10.1002/jcb.26210. [Epub ahead of print].

Wang XF, Huang WF, Nie J, Zhou Y, Tan DW, Jiang JH. Toxicity of chemotherapy regimens in advanced and metastatic pancreatic cancer therapy: a network meta-analysis. J Cell Biochem. July 6, 2017. doi: 10.1002/jcb.26266. [Epub ahead of print].

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