In malignant mesothilioma, chemotherapy is administered to prolong survival, improve quality of the patient’s life, and provide symptomatic relief. As of now, there is no individual drug or combination treatment plan that can be presented as the standard treatment for mesothelioma. A number of single drugs and combination treatment regimes have been tested in clinical trials and the response rates of these vary between 0-45%.
An assessment of studies by Berghmans et al showed that cisplatin, as a single agent, was the most effective in the treatment of mesothelioma along with carboplatin showing similar activity. Cisplatin when used in combination with doxorubicin rendered a superior response rate in comparison to other regimes, although there is no clear evidence that shows its benefits in terms of survival. Individual drugs such as vinorelbine and combination treatment regimes such as MVP (mitomycin C, vinblastine and cisplatin) are other drugs that also provide improved symptomatic relief with acceptable levels of toxicity.
Recently, use of agents such as the antifolate pemetrexed (Alimta; Eli Lilly) has generated much interest. Pemetrexed works by hindering folate dependent synthesis of purines and pyrimidines (the basic building blocks of DNA and RNA). A Cochrane review in terms of the effectiveness of combination treatment regime involving cisplatin/pemetrexed indicates a survival benefit. Increased toxicities have been recorded with this combination treatment, but it can be controlled by co-administering vitamin B12 and folate supplements. Most of the evidence that supports the use of pemetrexed has been sourced from a single study involving 331 patients, all of whom were co-administered vitamin B12 supplements. Patients treated with combination pemetrexed/cisplatin recorded a median survival of 13.3 months whereas those treated with cisplatin alone (p = 0.05) had a median survival rate of 10.0 months. The combination treatment also resulted in improved quality of life and better symptomatic relief in comparison to cisplatin alone. However, replacing cisplatin with carboplatin in the combination treatment can have similar efficacies with reduced side effects. Raltitrexed, an alternative antifolate agent, has also shown to improve survival when used in combination with cisplatin. Median survival rates increased from 8.8 months (CI 7.8–10.8 – when only cisplatin was used) to 11.4 months (CI 10.1 to 15 – when a combination of cisplatin-raltitrexed (p=0.05)) was used. While the study has only borderline significance due to its sample size, the results imply that a combination of cisplatin and an antifolate should be a part of the combination treatment in mesothelioma. Recent advances show a preference for neoadjuvant chemotherapy, after which EPP and radiation therapy can be administered to treat malignant mesothelioma. A study recently published by Weder et al demonstrates their experience with a prospective neoadjuvant chemotherapy trial involving cisplatin and gemcitabine and followed by EPP. The median survival rate for this particular study was 23 months. Similarly, Flores et al studied patients who were administered induction gemcitabine and cisplatin and underwent EPP subsequently. Median survival for all patients was 19 months in this.
study, but those patients who completed chemotherapy and underwent EPP as well registered a median survival of 33.5 months.
Based on these results, it is necessary that all patients who may be
fit (ECOG performance status 0–2), be provided the opportunity to discuss
the benefits of chemotherapy with an oncologist. This should be done with
the knowledge that there is no published data or information that may
compare survival or symptom control in patients who were administered
chemotherapy or the most appropriate supportive care only. The first (MSO-1)
of these trials has been completed and preliminary results were published
in 2007 in abstract form. The results show that including chemotherapy
in active symptom control (involving best supportive care) did not result
in a significant survival benefit. However, this trial was initiated prior
to the emergence of pemetrexed.