Clapper, Patti, Schweizer and Mason

According to the results of a Japanese study published in Oncology Reports, two popular chemotherapy drugs used to treat mesothelioma could be interacting in unexpected ways when used in conjunction. 

Cisplatin, a general chemotherapy drug, has been used for decades to treat a wide variety of cancers and is considered the “go-to” chemotherapy drug where mesothelioma is concerned.  Doctors use this drug most often because it is regarded as comparatively safe, relatively inexpensive, and has shown promising results in both clinical trials and non-experimental settings.  Cisplatin is regularly combined with other chemotherapy drugs including carboplatin.  It is also regularly used in conjunction with pemetrexed, also known as Alimta under the brand name.

Pemetrexed, developed by Ely Lilly, is the first chemotherapy drug approved by the FDA to specifically treat mesothelioma in 2009.  Since then, pemetrexed has quickly gained acceptance as a frontline drug for chemotherapy for mesothelioma patients. 

For even better success, a combination or multimodal mesothelioma treatment approach is the most common, hence the combining of two different chemotherapy drugs such as Pemetrexed and Cisplatin.  However, nobody has really examined how these two drugs interact when used together.

A team of researchers led by Miyako Kitazono-Saitoh from the Department of Respirology at the Graduate School of Medicine of Chiba University in Japan set out to do just that.  They suspected that the two drugs could very well have unexpected results within an individual mesothelioma patient. 

Mainly they were looking to see if there is any cross-resistance to one of the two drugs which would then decrease the efficacy of treatment. 

The team used clonogenic assays followed by isobologram analysis utilizing four separate human malignant pleural mesothelioma cell lines.  The samples were exposed to regularly increasing doses of the two drugs to establish two distinct drug-resistant sublines – one group of samples was resistant to cisplatin, the other to pemetrexed.

These individual test groups were then treated with combinations of cisplatin and pemetrexed, as would happen in a real world therapeutic setting.  Upon examining the data from the four individual test groups within the cisplatin-resistant samples, researchers discovered that “cisplatin and pemetrexed had synergistic effects in 3 cell lines and an additive effect in the fourth cell line.”  Until that point, it appeared as if the two drugs did indeed work well with each other.  This meant that pemetrexed did indeed help to fight samples that were resistant to cisplatin. 

However, the opposite could not be proven with such clarity.  The pemetrexed-resistant cells treated with cisplatin showed a wide variety of responses to the drug.  Still, researchers did conclude that the reactions they recorded within both test groups were within respectable margins and suggested “the clinical relevance of [pemetrexed and cisplatin] combination in chemotherapy.” 

The study really just clarified what mesothelioma doctors had already suspected – that a combined form of chemotherapy with cisplatin-based treatment in addition to pemetrexed was one of the most effective ways to treat the disease.