The role of pemetrexed in lung adenocarcinoma, mixed subtype with bronchioloalveolar carcinoma features

Our plain-English summary of The role of pemetrexed in lung adenocarcinoma, mixed subtype with bronchioloalveolar carcinoma features, by M. Duruisseaux, J. Cadranel, M. Pérol, et al (Current Drug Targets, 2010).

The study

• Authors: M. Duruisseaux, J. Cadranel, M. Pérol, D. Arpin
• Journal: Current Drug Targets
• Published: 2010;11(1):74-7
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Bronchioloalveolar carcinoma (BAC) and adenocarcinoma with bronchioloalveolar features (ADC-WBF) belong to the same anatomo-clinical entity and show very similar epidemiologic, clinical and biological characteristics. However there is a lack of consensus for the treatment of unresectable forms. Although epidermal growth factor receptor tyrosine kinase inhibitors and paclitaxel do have some efficacy, the aim of this review is to assess the role that pemetrexed, a new generation antifolate, could play in this context. Pemetrexed has proved to be particularly effective in advanced lung adenocarcinomas and unresectable mesotheliomas, and cases of major and sustained responses of ADC-WBF to pemetrexed have been reported. The preclinical rationale explaining this efficacy is that it inhibits the growth of BAC cell lines in vitro. BAC tumors overexpress FR-alpha, a protein involved in pemetrexed intracellular transport, at rates higher than those observed in lung adenocarcinomas and mesotheliomas and it would seem that pemetrexed efficacy is correlated to FR-alpha expression. The role played by thymidylate synthase expression level in sensitivity to pemetrexed also needs to be specifically explored in ADC-WBF. The results of two phase II trials, SWOG 0526 and IFCT 05-04, will hopefully provide decisive information on the relevance of pemetrexed in ADC-WBF management and the molecular predictors of response.

In plain English

This article was a review, not a new study. The authors reviewed published and preliminary data on pemetrexed, a cancer drug, for a lung cancer called adenocarcinoma mixed subtype with bronchioloalveolar carcinoma features (ADC-WBF). It did not study asbestos. Mesothelioma came up where pemetrexed with cisplatin was called the standard of care in unresectable malignant pleural mesothelioma, and in cited laboratory work on mesothelioma cell lines. Earlier trials had shown response rates of 14 and 11% with paclitaxel and 17-22% with EGFR tyrosine kinase inhibitors. The authors cited laboratory work in which pemetrexed inhibited BAC cell lines. In the same work, expression of a folate receptor, FR-alpha, estimated by mRNA microarrays, was 2 and 2.6-fold higher in BAC than in mesothelioma and non-BAC lung adenocarcinoma, respectively. They noted their own earlier report of two patients whose pemetrexed responses were maintained over 16 and 24 months. They also cited unpublished trial data: pemetrexed, given as third- or later-line treatment, achieved disease control in 10 of 13 patients. The authors stated that published data were too limited for a consensus. They concluded that further investigations were needed.

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: Review of published literature and preliminary trial data
• Who was studied: No new study population. The review covered published studies, cell-line work and trials on bronchioloalveolar carcinoma (BAC) and adenocarcinoma mixed subtypes with BAC features (ADC-WBF).
• Exposure: The drug pemetrexed, an antifolate. Paclitaxel and EGFR tyrosine kinase inhibitors were discussed for comparison. No asbestos exposure was studied.
• Main results:
  • In two earlier phase II trials of paclitaxel for advanced ADC-WBF (77 patients in total), response rates were 14% and 11%.
  • In earlier phase II trials, response rates were 11-14% with paclitaxel versus 17-22% with EGFR tyrosine kinase inhibitors.
  • The article described pemetrexed with cisplatin as the standard of care in unresectable malignant pleural mesothelioma, citing another study.
  • In cited laboratory studies, mesothelioma cell lines had a high level of FR-alpha expression, and this level was correlated with the cytotoxic activity of pemetrexed.
  • In a cited laboratory study, pemetrexed inhibited BAC cell lines in vitro.
  • In the same cited study, FR-alpha expression estimated by mRNA microarrays was 2-fold and 2.6-fold higher in BAC than in mesothelioma and non-BAC lung adenocarcinoma, respectively.
  • In the authors' earlier report of two patients with advanced ADC-WBF, responses to pemetrexed were maintained over 16 and 24 months.
  • In the IFCT 04-01 trial, pemetrexed given as third- and further-line therapy achieved disease control in 10 of 13 patients. These data come from a manuscript described as in preparation.
  • The authors stated that, to their knowledge, no data had been reported on thymidylate synthase (TS) expression level in ADC-WBF.
  • Two phase II trials were closed but their results were not yet available. One was IFCT 05-04, with more than 130 previously untreated patients. The other was a SWOG trial, with 99 patients with advanced BAC.
• The authors' conclusion: The authors concluded that recent results suggest clinical activity of chemotherapy in BAC and ADC-WBF. They said further investigations are needed to explore pemetrexed's efficacy in ADC-WBF and molecular predictors of response, notably TS and FR-alpha expression.
• Limitations the authors state:
  • The authors stated there were not enough published data on treatment of ADC-WBF, including no phase III trial publications, to establish a consensus.
  • The authors stated that ADC-WBF were not analyzed separately in the phase III trials of pemetrexed, so few data were available.

Topics

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

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Lung Adenocarcinoma, Carcinoma, Adenocarcinoma, Unresectable, Tyrosine Kinase Inhibitor, Antifolate, Mesothelioma.

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