Mesothelioma Information - Mesothelioma Treatment
The response rate decreases with increasing number of patients, and the value of that agent is now modest, despite early encouraging results.146,310 A higher dose of doxorubicin (90 mg/m2 divided over 3 consecutive days) with the addition of external radiotherapy combined with half-dose doxorubicin during cycle 2, yielded a 21% response rate (1 complete response [CR] and 2 partial responses [PRs]) in 14 patients with pleural mesothelioma and no response in 2 patients with peritoneal mesothelioma.63
The high response rate reported for detorubicin, an analogue of doxorubicin, needs confirmation.70 High doses of cisplatin (80 mg/m2 weekly for six courses, or 40 mg/m2/d for 5 days) appear to produce more partial responses than regular doses of that agent but no complete response. The activity of mitomycin, initially discovered in a nude mouse model,61 has been confirmed clinically.19
Paclitaxel (Taxol) has so far shown only modest activity, but these results are preliminary. Dihydro-5-azacytidine was evaluated in mesothelioma because of its selective toxicity for serosal membranes leading to pleuritis and pericarditis. Its activity as a single agent and combined with cisplatin has been low, however (see Tables 89.7 and 89.8). Vinca alkaloids (vinblastine, vincristine, vindesine) and mitoxantrone have virtually no activity, but a recent trial of vinorelbine showed a 21% response rate.251a The antifols (methotrexate, edatrexate, trimetrexate) seem to show activity. Results with high-dose methotrexate need confirmation.
An apparently active new agent is the novel experimental multi-targeted antifolate (MTA LY231514), which produced 4 responses among 7 patients with mesothelioma and is currently being evaluated in combination with cisplatin.266a Results with the taxane drugs as single agents have been disappointing. Onconase is a ribonuclease isolated from the eggs of the leopard frog and has been reported to produce 4 partial responses in 25 patients with mesothelioma.71b A randomized trial is currently underway prospectively comparing that agent with doxorubicin.
Some successes have occasionally been observed with the use of 5-fluorouracil (5-FU), oral melphalan,178 methyl glyoxalbisguanylhydrazone, 58 and prolonged oral etoposide,243 although a large trial of oral or intravenous etoposide yielded a low response rate of 6%.230a Few complete responses are seen with single agents, and median survival when reported, is usually between 6 to 9 months from treatment.
Search for more active agents is needed by using all the available clinical and experimental resources. An in vitro chemosensitivity assay revealed that actinomycin D was the most effective of eight cytotoxic drugs tested, but clinical correlation is lacking at this time.37
Combination Chemotherapy
Combination chemotherapy is difficult to evaluate, since data on the single agent components are still scarce. Results compiled in Table 89.8 reveal that in most series including more than 10 patients, overall response rates remain below
Biologic and Other Therapies
Human recombinant IFN-‡ was first shown to potentiate the effect of chemotherapy (cisplatin or mitomycin) in a nude mouse model of mesothelioma.242 Preliminary results in patients suggest that IFNs may have some activity against mesothelioma. Recombinant human IFN-‡ given intrapleurally was reported to produce 2 partial responses in 13 patients with pleural mesothelioma.67 The combination of cisplatin and IFN-‡ given systemically produced a 32% response rate in 37 patients with pleural mesothelioma.269 Another trial of weekly systemic administration of cisplatin and IFN-‡ produced 1 CR and 4 PRs in 13 patients.201a
Another regimen combining systemic cisplatin and IFN-‡ with the addition of tamoxifen resulted in a 21% response in 34 patients,195 while the addition of mitomycin resulted in a 23% response rate in 43 patients.180a Intrapleural human recombinant IFN-‡ was recently found to be active in early mesothelioma where pleural nodules measure < 5 mm. Four CRs and 1 PR were seen in 9 patients with stage I mesothelioma, versus only 1 PR in 10 patients with stage II disease.34
A larger trial in 89 patients yielded an overall response rate of 20%, with 45% for stage I disease.36 IFN-‹ has also been active in vitro against human mesothelioma cell lines.37 On the other hand, IFN-‰ produced no response in 14 patients with mesothelioma.287
Similarly, the effects of IL-2 and LAK cells on immunologic abnormalities secondary to asbestos exposure or mesothelioma, as discussed above, provide a rationale for the clinical trial of such immunotherapy. Preliminary reports of the effect of intrapleural IL-2 showed 4 partial remissions in 17 patients with mesothelioma, with acceptable toxicity,90,266 and another report in 22 cases showed 1 CR and 11 PRs.16a
Further evaluation of these biologic treatments, alone and in combination with chemotherapy, is warranted. Interesting experimental observations in transplanted human mesothelioma in nude mice include 'cure' by injecting mice with diphtheria toxin,205 and decreased tumor growth by photodynamic therapy,98 which has also been effective in vitro against human mesothelioma cells.139
Mesothelioma Information
There are three types of mesothelioma that one can suffer from: pleural mesothelioma, peritoneal mesothelioma and pericardial mesothelioma. Mesothelioma symptoms vary dependent on the type of mesothelioma that one suffers from. The most common presenting symptom of mesothelioma is chronic chest pain associated with fluid buildup inside the pleural space; this is called pleural effusion.
Mesothelioma treatment options include surgery, chemotherapy, radiation therapy, photodynamic therapy, immunotherapy and gene therapy; however, none have thus far been able to combat the deadly cancer type.