Single agent chemotherapy drugs for mesothelioma
There are several chemotherapeutic agents that may be active in the treatment of mesothelioma. Doxorubicin appears to have some activity against mesothelioma. Response rates vary widely in different series of reports. Methotrexate with rescue, 5-azacytidine, and 5-flurouracil may have single agent activity against mesothelioma. Cisplatin or paclitaxel does not have significant single agent activity against mesothelioma.
Biological therapies in malignant mesothelioma
In mouse model experiments with mesothelioma human recombinant interferon alpha has been shown to improve the effectiveness of chemotherapy consisting of cisplatin or mitomycin (Ref 1). Results of clinical trials with human recombinant interferon alpha suggests that this effect may be true in humans as well. Recombinant human interferon alpha given intrapleurally has resulted in 2 partial responses among 13 patients with pleural mesothelioma. (Ref 2). The combination of cisplatin and interferon alpha systemically has produced response rates in the range of 32% among 37 patients with pleural mesothelioma (Ref 3). A study by Purohit et al (Ref 4) has shown that weekly systemic administration of cisplatin and interferon has produced 1 CR and 4 PRs in 13 patients. Addition of Tamoxifen to the regimen of cisplatin and alpha interferon has resulted in 21% response in 34 patients (Ref 5) while the addition of mitomycin resulted in a 23% response rate in 43 patients (Ref 6).
Interferon gamma ha been shown to be active when used intrapleurally. Boutin et al (Ref Ref 7). has shown that interferon is administered intrapleurally results in reduction in tumor size and complete responses. In this series the response rate was 20 percent. The main side effects were hyperthermia, liver toxicity, neutropenia and catheter related infections.
Astoul et al has reported 50 percent response rate in a series of 22 patients with one patient achieving complete response. The median survival in this study was 18 months (Ref 7).
Combination chemotherapies in malignant mesotheliomas
Several combinations have been studied in malignant mesotheliomas. Response rates in these studies vary widely from 0% to 48%. The highest reported response rate is for the combination of cisplatin and gemcitabine (48% in a series of 21 patients)
Randomized clinical trials in malignant mesothelioma
Mesothelioma is a rare disease and not many randomized clinical trials are available in malignant mesothelioma management. Combination of doxorubicin and cyclophosphamide had shown a 7% response rate in a large randomized clinical trial in patients with advanced stage malignant mesothelioma.(Ref 8) Cancer and Leukemia group study with 79 patients showed that combination of doxorubicin and cisplatin produces response rates in the range of 24%, and median survival of 8.8 months.(Ref 9).
Randomized trials of intrapleural chemotherapy
Chemo drugs are often used intrapleurally to control pleural effusion in patients with advanced mesothelioma. A randomized study of patients with advanced mesothelioma patients by Lung Cancer Study Group has showed that intrapleural cisplatin plus cytarabine produces at least 75% reduction in pleural effusion in about half of all patients.
- Sklarin NT, Chahinian AP, Feuer EJ, et al. Augmentation of activity of cisdiamminedichloroplatinum (II) and mitomycin C by interferon in human malignant mesothelioma xenografts in nude mice. Cancer Res 1988;48:64.
- Christmas TI, Musk AW, Robinson BWS. Phase II study of recombinant human alpha interferon therapy in malignant pleural mesothelioma. Proc Am Assoc Cancer Res 1990;31:283.
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- Purohit A, Moreau L, Dietemann A, et al. Weekly systemic combination of cisplatin and interferon a2a in diffuse malignant pleural mesothelioma. Lung Cancer 1998;22:119.
- Pass HI. Contemporary approaches in the investigation and treatment of malignant pleural mesothelioma. Chest Surg Clin North Am 1994;4:497
- Metintas M, Ozdemir N, Ucgun I, et al. Cisplatin, mitomycin, and interferon-a2a combination chemoimmunotherapy in the treatment of diffuse malignant pleural mesothelioma. Chest 1999;116:391.
- Boutin C, Nussbaum E, Monnet I, Bignon J, Vanderschueren R, Guerin JC, Menard O, Mignot P, Dabouis G, Douillard JY. Intrapleural treatment with recombinant gamma-interferon in early stage malignant pleural mesothelioma. Cancer. 1994 Nov 1;74(9):2460-7.
- Samson MK, Wasser LP, Borden EC, et al. Randomized comparison of cyclophosphamide, imidazole carboxamide, and adriamycin versus cyclophosphamide and adriamycin in patients with advanced stage malignant mesothelioma: a Sarcoma Intergroup Study. J Clin Oncol
- Chahinian AP, Antman K, Goutsou M, et al. Randomized phase II trial of cisplatin with mitomycin or doxorubicin for malignant mesothelioma by the Cancer and Leukemia Group B. J Clin Oncol 1993;11:1559.