Category: Mesothelioma

Despite many investigations, no chemotherapeutic protocol has yet emerged as an effective treatment for malignant pleural mesothelioma. Previous studies have been hindered by small size, inability to accurately measure disease extent, absence of a precise staging system, and lack of knowledge regarding the natural history of the disease. Cohesive, multi-institutional studies have become necessary to approach this disease in an efficient manner.
Among the chemotherapy agents that have been tested, the anthracyclines, platinum compounds, and alkylating agents have demonstrated small but real activity against mesothelioma. Preliminary evidence suggests an advantage to dose-escalated administration of doxorubicin and cisplatin, indicating that mesothelioma may not be totally chemotherapy-resistant, and further investigations with such dosing regimens may be warranted. …Read the rest of this article

A Review of Chemotherapy Trials for Malignant Mesothelioma: Cisplatin-Based CombinationsAmong the cisplatin-based regimens, cisplatin given with mitomycin in one arm of CALGB 8435 resulted in a 26% response rate, including two CRs. Tsavaris et al evaluated cisplatin (100 mg/m2) combined with vinblastine (6 mg/m2) in 20 patients, reporting one CR and four PRs (25% response) with a 13-month mean duration of response. One study in which cisplatin (70 mg/m2/wk for 6 of 7 weeks) was administered with oral etoposide (50 mg/d) to 25 patients resulted in one CR and five PRs (24% response),78 whereas another study reported a 12% response rate with this combination. Cisplatin has also been tested in combination with DHAC and with pirarubicin, but no improvements over single-agent cisplatin therapy were reported. …Read the rest of this article

Combination chemotherapy regimens have been evaluated in a number of studies, but have not shown any clear advantage over single-agent chemotherapy (Table 5). Most combination chemotherapy studies have included doxorubicin, cisplatin, or an alkylating agent, reflecting the popularity of these drugs based on their mild efficacy in single-agent trials.
Doxorubicin-Based Combinations
Doxorubicin has been combined with alkylating agents in more than five separate studies. Doxorubicin (60 mg/ m2) in combination with cyclophosphamide (500 mg/m ) resulted in an 11% response rate among 36 patients; the addition of dacarbazine (250 mg/m2) did not improve response in the other study arm of this trial (13% response rate among 40 patients). However, an older study reported a 25% response rate in 20 patients given these three agents at higher doses (doxorubicin, 60 to 90 mg/m2; cyclophosphamide, 600 to 900 mg/m2; and dacarbazine, 1 g/m2). Carmichael et al70 reported a 12.5% response rate among 16 patients given doxorubicin (40 mg/m2) with ifosfamide (5 g/m2). …Read the rest of this article

A Review of Chemotherapy Trials for Malignant Mesothelioma: AntimetabolitesAntimetabolites
The antifolates have shown promise in the treatment of malignant mesothelioma. A favorable response rate of 37%, including one complete response (CR), was shown by Solheim et al in a group of 60 patients who received high-dose methotrexate (3 g total dose at 10- and 21-day intervals).
Variable activity has been seen with two newer antifolates, trimetrexate and edatrexate, in trials by the CALGB. In the trimetrexate study, two dose regimens used sequentially (6 and 10 mg/m2) yielded a 12% PR rate in both arms, with no CRs. Patients receiving the higher dose demonstrated a longer median survival (8.9 months vs 5 months in the lower-dose group), suggesting a possible advantage for higher-dose therapy with this class of agents. Both dose groups, however, had the same 2-year survival rate (18%). canadian neightbor pharmacy
…Read the rest of this article

Plant Alkaloids
The vinca alkaloids have not shown activity against mesothelioma. Vindesine produced only one response among 17 patients in a series using 3 mg/m2/wk and no responses in a study of 2 mg/m2/wk Single trials of vinblastine and vincristine have been equally disappointing, with no responses observed in either study.
Poor results have also been seen with low-dose oraletoposide (100 mg/d), which yielded only one PR (4% response rate) in a trial of 23 patients.44 Smaller studies using either oral or IV etoposide have not shown any responses. canadian health & care mall

The CALGB tested paclitaxel at a dose of 250 mg/m2, and only three disease regressions were observed among 35 patients (9%). The European Organization for Research and Treatment of Cancer has recently reported a similarly low response rate for this agent. …Read the rest of this article

A Review of Chemotherapy Trials for Malignant Mesothelioma: Single-Agent ChemotherapyNumerous single agents have been tested for activity against mesothelioma. In the past, many small studies reported relative success, but these may have represented a bias toward publishing positive results. Such favorable outcomes have usually not been confirmed by larger, follow-up series. Table 4 summarizes the larger singleagent chemotherapy trials that have included 15 patients. Smaller trials have not been included in Table 4, but some are mentioned in the text. canadian health&care mall

Anthracyclines/DNA Intercalating Agents
Historically, the anthracyclines have been considered to be active against mesothelioma, although larger and more recent trials have shown no more than modest efficacy among these agents. Doxorubicin, the most commonly cited anthracycline, has been used in a number of studies over the last 2 decades. This drug has demonstrated some definite activity against mesothelioma, with overall response rates of 10 to 20%.23 In larger trials, the results have been variable. Sorensen et al reported no responses among 15 patients who were given doxorubicin at a dose of 60 mg/m2, whereas Lerner et al noted a 14% response rate among 51 patients given the same dose. Most studies of doxorubicin have used doses <75 mg/m2 given every 3 weeks. High er-dose doxorubicin trials may be warranted, as several reports of combination chemothera-py6o,ei have suggested increased efficacy with dose-escalated doxorubicin. …Read the rest of this article

The role of systemic chemotherapy for malignant pleural mesothelioma continues to be an area of active investigation. Numerous agents have been tested over the years, but few have shown any clear benefit, and no regimen has emerged as a standard of care. Because of the rarity of the disease, most trials have been small and therefore lacking in statistical significance. Trials performed before the advent of CT scanning could not accurately measure disease extent and were fraught with inaccuracies. Structured, multi-institutional trials have become necessary to gather reasonable data on the use of chemotherapy in mesothelioma. The Cancer and Leukemia Group B (CALGB) began its mesothelioma program in 1984 with the hope of performing structured chemotherapy trials and pooling the resources of multiple institutions. To date, seven trials with a total of 337 eligible patients have been completed (Table 1).

Interpretation of the data obtained using various treatment protocols for malignant pleural mesothelioma has been hindered by lack of a precise and universal staging system for the disease. The International Mesothelioma Interest Group has proposed a new tumor nodes metas-tases (TNM) staging system that expands on previous systems (Table 2). The system incorporates new data from recent studies regarding the natural history of the disease. Systematic application of such a staging system will allow more accurate planning and precise assessment of future therapeutic trials. …Read the rest of this article