Elsevier

Lung Cancer

Volume 73, Issue 3, September 2011, Pages 351-355
Lung Cancer

Platinum-based doublet chemotherapy in pre-treated malignant pleural mesothelioma (MPM) patients: A mono-institutional experience

https://doi.org/10.1016/j.lungcan.2011.01.005Get rights and content

Abstract

Background

The major clinical problems of MPM management are the short duration of response and the early relapse. Currently, after the first-line standard pemetrexed/platinum combination there is not a defined regimen for the second line treatment of MPM, and the clinical benefits in fit patients are uncertain. We analyzed the feasibility of gemcitabine/platinum chemotherapy in pretreated MPM patients.

Methods

Eligible patients should have relapsed after first-line chemotherapy with pemetrexed plus cisplatin (24%) or carboplatin (76%); 53% of the patients had previously received trimodality treatment, 18% neoadjuvant chemotherapy followed by pleurectomy/decortication, 29% were inoperable. Patients had to have PS = 0–2, adequate organ function, measurable disease.

Chemotherapy was gemcitabine 1000 mg/m2 days 1, 8 associated to the alternative platinum compound respect to 1st line, i.e. cisplatin 75 mg/m2 or carboplatin AUC 5 day 1 every 3 weeks, for 3–6 cycles. Baseline staging and reassessment after cycles 3 and 6 were performed with CT-scan.

Results

Since 2006 17 relapsed MPM patients were referred to our centre. Patients were 12 males and 5 females; median age: 61 years (range 47–74); histology: 12 epithelial, 4 sarcomatoid and 1 biphasic. PS 1–2 (15:2).

The combination of gemcitabine with carboplatin/cisplatin was administered as second line treatment in 13 (76%) patients, as third line in 4 (24%) patients. Two patients were lost to follow-up without re-evaluation, therefore radiologic and clinical response was assessable in 15 (88%) patients. Among evaluable patients 10 (67%) showed stable disease and 5 (33%) progressive disease. Symptoms improved in 8 (53%) cases. In the intent-to-treat population median survival was 28 weeks (range 13–168) and median time-to-treatment failure 15 weeks (range 3–75).

Toxicity profile showed 2 (13%) grade 4 and 6 (40%) grade 3 thrombocytopenia, 4 (27%) grade 3 leucopenia, 3 (20%) grade 3 anaemia and 6 (40%) of grade 3 neutropenia. Grade 3 non haematological toxicities were nausea (14%) and asthenia (21%).

Conclusion

Gemcitabine-platinum regimens are able to control symptoms and disease progression with a modest toxicity profile. The present results from a small series of patients should be confirmed by a prospective trial in a larger cohort of patients.

Introduction

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and increasing incidence in industrialized countries. MPM has been linked to chronic inhalation of asbestos fibres and the epidemiologic data foresee a sharp rise of MPM incidence and mortality in the next fifteen years.

In cases not eligible for radical surgery the current treatment is a cisplatin-based chemotherapy combined with antifolate drugs, namely pemetrexed or raltitrexed. A mean overall survival of 12.1 and 11.4 months was obtained with the two combinations respectively, longer than that with single agent cisplatin (9.3 and 8.8 months) [1], [2]. Median time to progression (TTP) and response rate (RR) are significantly greater in the pemetrexed/cisplatin and raltitrexed/cisplatin arms compared to the single agent arms: TTP 5.7 vs 3.9 and 5.3 vs 4 months, RR: 41.3% vs 16.7% and 24% vs 14%, in the two studies respectively [1], [2]. The major clinical problems of MPM management are the short duration of response and the early relapse.

Second-line therapies are being increasingly used in the clinical practice because patients frequently still have a good performance status at the time of disease progression.

After the standard first-line pemetrexed/platinum combination there is not a defined regimen for the second line treatment of MPM, and the clinical benefits in fit patients are uncertain.

A number of phase II trials have exploited different chemotherapeutic and targeted agents, but results have been generally poor. Several phase II trials and a large randomised phase III study are ongoing, and hopefully could report positive results [3].

Combination chemotherapy with gemcitabine plus cisplatin [4], [5], [6], [7], [8] or carboplatin [9], [10] is considered a valid option as first-line treatment in inoperable MPM patients or as a part of a trimodality treatment. So far, no prospective trial testing the activity of those associations in the second line setting has been performed, even if recent evidences suggest the feasibility of phase II chemotherapy trials with gemcitabine in combination after pemetrexed/platinum therapy [11].

The primary endpoint of the present study was to assess the feasibility in terms of tolerability and activity of gemcitabine/platinum chemotherapy in pretreated MPM patients by a retrospective analysis of response, toxicity and survival data.

Section snippets

Patients and methods

Since 2006 all the patients with histologically confirmed malignant pleural mesothelioma who were referred to our centre were evaluated for the inclusion in the study.

Eligible patients should have relapsed after first-line chemotherapy with pemetrexed plus cisplatin or carboplatin; patients had to have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0–2, adequate bone marrow, renal and hepatic function, and measurable disease according to modified Response Evaluation Criteria in

Results

Since 2006 17 relapsed MPM patients were included in the study.

Patients were 12 males and 5 females, median age was 61 years (range 47–74). The histotype was epithelial in 12 (70%), sarcomatoid in 4 (24%) and biphasic in 1 (6%) patients; 15 patients had a ECOG PS 1, 2 patients had a PS 2.

First-line chemotherapy was pemetrexed plus cisplatin in 4 (24%) or plus carboplatin in 13 (76%) patients. Trimodality treatment was feasible in 9 (53%) patients; 3 (18%) patients underwent

Discussion

Malignant pleural mesothelioma is a chemoresistant neoplasm, with frequent disease relapses after first line chemotherapy. So far, most of the randomised trials in MPM have been focused on first-line chemotherapeutic regimens, and the clinical benefit of the second-line treatment has still to be proved.

A retrospective analysis of the first-line phase III trial by Vogelzang et al. showed a potential impact of post-study chemotherapy (PSC) on the overall survival of pre-treated patients [11],

Conflict of interest statement

None of the authors has any potential conflict of interest.

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