Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study

Our plain-English summary of Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study, by N. Katirtzoglou, I. Gkiozos, N. Makrilia, et al (Clinical Lung Cancer, 2010).

The study

• Authors: N. Katirtzoglou, I. Gkiozos, N. Makrilia, E. Tsaroucha, A. Rapti, G. Stratakos, G. Fountzilas, K.N. Syrigos
• Journal: Clinical Lung Cancer
• Published: 2010;11(1):30-5
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is a rapidly progressive tumor that is increasing in frequency worldwide. Treatment options are limited, and response to chemotherapy is poor. The aim of this phase II study was to evaluate the activity of the carboplatin/pemetrexed combination as first-line chemotherapy in patients with unresectable MPM.

Patients And Methods: Chemotherapy-naive patients with histologically confirmed MPM and an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled. Treatment consisted of pemetrexed 500 mg/m2 and carboplatin area under the concentration-time curve of 5 mg/mL/min, both administered on day 1 of a 21-day cycle. The treatment continued until 6 cycles were completed or until unacceptable toxicity or disease progression were observed.

Results: A total of 62 patients were enrolled. Of these patients, 18 (29%) had a confirmed partial response, whereas the disease remained stable in 34 patients (54.9%) and progressed in 10 patients (16.1%). The median overall survival (OS) was estimated at 14 months (95% CI, 11.8-16.2 months), and the median time to progression was 7 months (95% CI, 5.8-8.2 months). The difference in median OS between the epithelial histologic subtype (16 months) and the sarcomatoid subtype (11 months) was statistically significant.

Conclusion: This study confirmed the activity of the carboplatin/ pemetrexed combination in the first-line treatment of patients with MPM. It is a viable option, especially in cases in which side effects are generally anticipated.

In plain English

This phase II study at two Greek hospitals tested carboplatin plus pemetrexed as first chemotherapy for malignant pleural mesothelioma unsuitable for curative surgery. From December 2004 to August 2007, 62 chemotherapy-naive patients received both drugs every 21 days for up to 6 cycles. Tumors partly shrank in 18 of 62 (29%), were stable in 34 (54.9%) and grew in 10 (16.1%); none disappeared completely. Median overall survival was 14 months (95% CI, 11.8-16.2) and median time to progression was 7 months (95% CI, 5.8-8.2). Median survival was 16 months (95% CI, 12.8-19.2) for 47 epithelioid-type patients versus 11 months (95% CI, 6.0-16.0) for 15 sarcomatoid-type patients, a statistically significant difference. Survival did not differ significantly by age, sex, stage or asbestos exposure. Severe (grade 3 or 4) neutropenia, a low count of neutrophils (a type of white blood cell), affected 15 patients (24.2%). No treatment-related deaths occurred. The authors concluded the combination is effective, well tolerated and viable when side effects are expected, such as in elderly patients. They noted their patients were fitter than those in earlier studies.

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: Phase II clinical trial (all patients received the same chemotherapy regimen)
• Who was studied: 62 chemotherapy-naive patients with histologically confirmed malignant pleural mesothelioma who were not candidates for curative surgery. They were enrolled from December 2004 to August 2007 at two centers in Greece: Sotiria General Hospital, Athens, and Papageorgiou Hospital, Thessaloniki.
• Exposure: The exposure studied was the treatment: pemetrexed 500 mg/m2 plus carboplatin AUC 5, both given on day 1 of a 21-day cycle for up to 6 cycles, with folic acid and vitamin B12. Asbestos exposure was recorded only as a patient characteristic.
• Main results:
  • In the intent-to-treat analysis of all 62 patients: 18 had a confirmed partial response (29%), 34 had stable disease (54.9%), and the disease progressed in 10 (16.1%).
  • No patient had a complete response.
  • For all patients, median overall survival was 14 months (95% CI, 11.8-16.2 months) and median time to progression was 7 months (95% CI, 5.8-8.2 months).
  • The study defined time to progression as the time to first documented progression or to death from any cause.
  • Median overall survival was 16 months in patients with the epithelioid type and 11 months in patients with the sarcomatoid type. The text describes the difference as statistically significant (P less than .05).
  • Table 2 gives the group sizes and confidence intervals. For the 47 epithelioid patients, median survival was 16.0 months (95% CI 12.8-19.2). For the 15 sarcomatoid patients, it was 11.0 months (95% CI 6.0-16.0). The log-rank P value was .01.
  • Survival showed no significant differences by age, sex, disease stage, or asbestos exposure.
  • Grade 3 or 4 neutropenia (low neutrophil count) occurred in 15 of 62 patients (24.2%), and 1 patient developed febrile neutropenia.
  • There were no treatment-related (toxic) deaths.
• The authors' conclusion: The authors concluded that carboplatin plus pemetrexed is effective and well tolerated in malignant pleural mesothelioma. In their view it is a viable option when side effects are expected, such as in elderly patients and patients with poor performance status.
• Limitations the authors state:
  • The authors stated that response rates are not a good basis for comparing studies, because there is no universally accepted assessment system and response correlates poorly with survival in this disease.
  • The authors noted that their patients had better performance status than patients in the earlier studies they compared with.

Topics

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

Medical terms in this study, explained in our Lexicon: Carboplatin, Pemetrexed (Alimta), Pleural Mesothelioma, Chemotherapy, Unresectable, Performance Status, Disease Progression, Median Overall Survival.

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• Phase II study of gemcitabine plus docetaxel as second-line treatment in malignant pleural mesothelioma: a single institution study — I. Tourkantonis, N. Makrilia, et al. (2011)
• First-line chemotherapy with pemetrexed plus cisplatin for malignant peritoneal mesothelioma — E. Fujimoto, T. Kijima, et al. (2017)
• A first-in-human phase I dose-escalation, pharmacokinetic, and pharmacodynamic evaluation of intravenous LY2090314, a glycogen synthase kinase 3 inhibitor, administered in combination with pemetrexed and carboplatin — J.E. Gray, J.R. Infante, et al. (2015)
• Sunitinib combined with pemetrexed and carboplatin in patients with advanced solid malignancies--results of a phase I dose-escalation study — N. Blais, D.R. Camidge, et al. (2013)
• A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol — N. Fujimoto, K. Aoe, et al. (2018)

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