Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany

Our plain-English summary of Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany, by M. Reck, R.A. Stahel, J. von Pawel, et al (Respiratory Medicine, 2010).

The study

• Authors: M. Reck, R.A. Stahel, J. von Pawel, M. Karthaus, S. Korfee, M. Serke, W.H. Schuette, C. Eschbach, T.H. Fink, M.I. Leschinger, C. Manegold
• Journal: Respiratory Medicine
• Published: 2010;104(1):142-8
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

An international expanded access program was initiated to provide access to treatment with pemetrexed prior registration and reimbursement for malignant mesothelioma (MM). Chemonaïve and pretreated patients with inoperable MM of the pleura or peritoneum were eligible. This report describes the results obtained in German centers. Investigators could choose between three treatments: Pemetrexed 500 mg/m(2) alone (P) or in combination with cisplatin 75 mg/m(2) (PC) or carboplatin AUC 5 (PCb). From November 2002 to June 2004, a total of 567 patients (554 with pleural MM; 41% pretreated) were included. Of 548 evaluable patients with pleural MM, 191 received P, 137 PC and 220 PCb. Patients in the P group were more often pretreated (70%) and had worse performance status compared with the other groups. In the P, PC, and PCb groups overall response rate (ORR) was 16%, 24% and 18%, median time to progression (TTP) was 5.5, 8.2, and 6.9 months, and median overall survival (OS) was 8.7, 11.3 and 9.7 months respectively. Efficacy outcomes were better for chemonaïve than for pretreated patients, and P was less hematotoxic than PC or PCb. Treatment of pleural MM with pemetrexed alone or in combination with platinum was safe and active as first and second-line therapy.

Copyright 2009 Elsevier Ltd. All rights reserved.

In plain English

This report covered German patients in an international program providing pemetrexed for malignant mesothelioma before commercial release. Doctors, not randomization, chose pemetrexed alone (more often for previously treated, less fit patients), with cisplatin, or with carboplatin. From November 2002 to June 2004, 567 patients enrolled at 14 German institutions; 554 had pleural mesothelioma. Among evaluable pleural patients, response rates were 24% (95% CI 17 to 32%) among 130 given cisplatin, 16% (10 to 22%) among 161 given pemetrexed alone and 18% (13 to 24%) among 207 given carboplatin, not significantly different. Median time to progression was 8.2 months (95% CI 7.0 to 8.6), 5.5 (4.9 to 7.2) and 6.9 (5.8 to 7.6) respectively, significantly different (p = 0.004). Median survival was 11.3 months (7.7 to undetermined), 8.7 (7.0 to undetermined) and 9.7 (7.1 to 10.9), not significantly different. However, 78% of patients were censored, meaning no death was observed during their available follow-up, which the authors said limits accuracy. Severe neutrophil and platelet drops occurred less often with pemetrexed alone. The authors concluded the treatments were safe and effective first- and second-line therapy for pleural mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Non-randomized, open-label expanded access program (treatment study); German subgroup of an international program
• Who was studied: 567 patients with inoperable malignant mesothelioma (554 pleural, 13 peritoneal), enrolled at 14 institutions in Germany from November 2002 to June 2004; the safety population with pleural mesothelioma was 548 patients (137 PC, 191 P, 220 PCb), of whom 498 were evaluable for response (130 PC, 161 P, 207 PCb)
• Exposure: Chemotherapy, not asbestos exposure: pemetrexed 500 mg/m2 with cisplatin 75 mg/m2 (PC), pemetrexed 500 mg/m2 alone (P), or pemetrexed 500 mg/m2 with carboplatin AUC 5 (PCb), chosen by the investigator
• Main results:
  • Among pleural mesothelioma patients, those in the pemetrexed-alone arm had worse Karnofsky performance status and had more often received prior treatment (70%, 131 of 187) than those in the carboplatin or cisplatin arms
  • Overall response rate in evaluable pleural patients: 24% (95% CI 17 to 32%) with PC (n=130), 16% (95% CI 10 to 22%) with P (n=161), 18% (95% CI 13 to 24%) with PCb (n=207); the difference was not significant
  • Median time to progression in pleural patients: 8.2 months (95% CI 7.0 to 8.6) with PC, 5.5 months (95% CI 4.9 to 7.2) with P, 6.9 months (95% CI 5.8 to 7.6) with PCb; the difference was significant (p = 0.004)
  • Median overall survival in pleural patients was 11.3 months (95% CI 7.7 to undetermined) with PC, 8.7 months (95% CI 7.0 to undetermined) with P and 9.7 months (7.1 to 10.9) with PCb
  • The difference in overall survival between arms was not significant (p = 0.606), and 78% of patients were censored
  • Median overall survival in pleural patients was 11.6 months for chemotherapy-naive patients and 8.6 months (95% CI 6.6 to 20.4) for previously treated patients
  • Grade 3/4 neutropenia and thrombocytopenia were observed less often in the pemetrexed-alone arm (neutropenia 16% vs 29% PC and 37% PCb, p less than 0.001; thrombocytopenia 7% vs 13% and 17%, p = 0.005); anemia and leukopenia were similar across arms
  • 3 patients (0.5%) died of adverse events probably or possibly related to study therapy
  • Of 12 evaluable peritoneal mesothelioma patients, 1 (8%) had a partial response and 8 (67%) had stable disease
• The authors' conclusion: The authors concluded that pemetrexed alone or combined with cisplatin or carboplatin was safe and effective as first- and second-line therapy in pleural mesothelioma
• Limitations the authors state:
  • There was no control arm
  • Patients were not randomly assigned; investigators chose the regimen based on patient condition and treatment intent
  • The high proportion of censored patients limits the accuracy of the survival estimates

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Mesothelioma, Pleura, Peritoneum, Cisplatin, Carboplatin, Performance Status, Median Overall Survival.

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