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Chemotherapy is divided into two general types: the first uses only one drug (single-agent), whereas the second applies two or more drugs during the treatment (combination).
There is not any outstanding success in mesothelioma treatment applying chemotherapy. Brief cancer degradation and the improvement of the symptoms were seen in 15-20 % of the clinical trials which used single agent chemotherapeutics. The average survival rate is about 9 months. The aim of chemotherapy is close to the one of radiation therapy, i.e. try to destroy the cancerous cells that could have rest within the body after surgery.
More promising results were shown by the doublets of platinum combined with novel cytotoxic agents e.g. pemetrexed, gemcitabine, or raltitrexed.
Pemetrexed acts by controlling TS (thymidylate synthase), DHFR (dihydrofolate reductase) and GARFT (glycinamide ribonucleotide formyl transferase), which are the enzymes that take part in the process of pyrimidine and purine synthesis. There is no agent that is aimed at all 3 enzymes so far, due to the fact that the target of the rest drugs (e.g. raltitrexed and 5-fluorouracil) is TS as well.
According to the statistics considerably longer median survival time was supervised in most cases, when patients received the combination therapy vs patients, who received only cisplatin.
Median time to progressive sickness was also considerably longer for patients in the cisplatin/ pemetrexed arm as against those in the cisplatin-only arm (5.7 months vs 3.9 months; HR = 0.68, P = .001). Tumor vulnerability (PR only), as gauged by CT scan, was supervised in 41.3% of patients in the cisplatin/pemetrexed arm vs 16.7% of patients in the cisplatin-only arm.
Gemcitabine is a cytosine arabinoside that is associated with pyrimidine antimetabolite. It has been shown to have extensive activity in different solid tumors, including mesothelioma. As its activity, as a particular substance matter is limited, so rates of response mostly have been higher, using it coupled with cisplatin.
Byrne and coworkers detected a 47.6% rate of response among 21 patients, who taking cisplatin 100 mg/m2 intravenously at the 1st day and gemcitabine 1000 m/m2 intravenously at the 1st, 8th and 15th days of a 28-day period for 6 cycles. Nearly ninety percent of patients experienced essential or complete feature relief. Nevertheless, in spite of these advantageous results, median duration of life was only 9.4 months. Toxicity was mostly confined to the hematologic and gastroenterologic systems: vomiting and grade 3 qualms appeared in 33% of patients, leukopenia appeared in 38% and grade 4 thrombocytopenia appeared in 19%.
Combination and single-agent chemotherapeutics have been estimated in single and combined modality researches. The doxorubicin is the most studied agent, which has produced imperfect responses in around 15% to 20% of patients' researches. Several combination chemotherapeutics regimens have been represented to have higher rates of response in small phase II trials; nevertheless, the toxic activity represented are still increased, and there is no substantiation that combination regimens conduce in longer control of symptoms or longer survival.
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