View source for Pemetrexed Cisplatin First Line

{{#seo:
|title=Pemetrexed + Cisplatin First-Line Mesothelioma: 12.1-Month Median OS
|title_mode=replace
|description=FDA-approved first-line chemotherapy for unresectable pleural mesothelioma. EMPHACIS trial outcomes, dosing, and current 2026 standing alongside immunotherapy.
|keywords=pemetrexed cisplatin mesothelioma, first-line chemotherapy mesothelioma, Alimta mesothelioma, Vogelzang 2003, EMPHACIS trial, mesothelioma chemotherapy regimen
|author=Rod De Llano, Founding Partner, Danziger & De Llano
|published_time=2026-05-21
|type=Article
|image=logo.png
|image_alt=WikiMesothelioma — Pemetrexed Cisplatin First-Line Mesothelioma
}}

{| class="infobox" style="width:280px; float:right; margin:0 0 1em 1em; border:2px solid #1a5276; border-radius:8px; overflow:hidden;"
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! colspan="2" style="background:#1a5276; color:white; padding:12px; font-size:1.05em; text-align:center;" | Pemetrexed + Cisplatin First-Line
|-
| style="padding:10px; font-weight:bold; width:45%; border-bottom:1px solid #dee2e6;" | FDA approval
| style="padding:10px; border-bottom:1px solid #dee2e6;" | 2004 (unresectable pleural mesothelioma)
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Pivotal trial
| style="padding:10px; border-bottom:1px solid #dee2e6;" | EMPHACIS (Vogelzang et al., 2003)
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Median OS (Pem+Cis vs Cis)
| style="padding:10px; border-bottom:1px solid #dee2e6;" | 12.1 vs 9.3 months
|-
| style="padding:10px; font-weight:bold; border-bottom:1px solid #dee2e6;" | Response rate
| style="padding:10px; border-bottom:1px solid #dee2e6;" | 41.3% (Pem+Cis arm)
|-
| style="padding:10px; font-weight:bold;" | Current standing
| style="padding:10px;" | First-line option alongside nivolumab + ipilimumab (CheckMate 743)
|-
| colspan="2" style="background:#1a5276; padding:8px; text-align:center; color:#e8f4f8; font-size:0.9em;" | <span data-nosnippet class="noai-content">Call (855) 699-5441 — Danziger & De Llano</span>
|}

== Executive Summary ==

'''Pemetrexed (Alimta) combined with cisplatin is the FDA-approved first-line chemotherapy regimen for unresectable malignant pleural mesothelioma.'''<ref name="lineage:00430dd1de644ca4bec077a05a927e75:d901b336a5f3fb9a">Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. ''J Clin Oncol''. 2003;21(14):2636-2644. PMID: [https://pubmed.ncbi.nlm.nih.gov/12860938/ 12860938].</ref> The regimen was established as standard of care after the EMPHACIS trial reported a median overall survival of 12.1 months for the combination versus 9.3 months for cisplatin alone, with a 41.3% response rate. The 2020 CheckMate 743 trial demonstrated that nivolumab plus ipilimumab provides longer overall survival in first-line treatment of unresectable pleural mesothelioma, but pemetrexed + cisplatin remains a recognized first-line option for patients who are not candidates for dual checkpoint inhibition.<ref name="lineage:00430dd1de644ca4bec077a05a927e75:c27c494b5110b48b">Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. ''Lancet''. 2021;397(10272):375-386. PMID: [https://pubmed.ncbi.nlm.nih.gov/33485464/ 33485464].</ref>

== At-a-Glance ==

* '''FDA approved 2004''' for unresectable malignant pleural mesothelioma in combination with cisplatin
* '''Pivotal evidence:''' EMPHACIS phase III trial (Vogelzang et al., 2003), pemetrexed + cisplatin vs cisplatin alone
* '''Median overall survival:''' 12.1 months (Pem+Cis) vs 9.3 months (Cis alone)
* '''Objective response rate:''' 41.3% in Pem+Cis arm
* '''Vitamin supplementation required''' — folic acid 350–1000 µg/day and vitamin B12 1000 µg every 9 weeks reduce hematologic toxicity
* '''Current standing:''' First-line alongside nivolumab + ipilimumab (CheckMate 743 backbone); pemetrexed + platinum remains widely used where dual checkpoint inhibition is not feasible
* '''Trial-design caveat:''' EMPHACIS predates immunotherapy era — modern selection criteria for first-line decisions weigh patient performance status, histology, and access to checkpoint inhibitors

== Mechanism and Regimen ==

Pemetrexed is a multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. The combination with cisplatin disrupts both DNA synthesis (pemetrexed via folate-dependent enzymes) and DNA cross-linking (cisplatin via platinum–DNA adducts), producing additive cytotoxicity in mesothelioma cell lines and patient tumors. Standard dosing is pemetrexed 500 mg/m² plus cisplatin 75 mg/m², both administered intravenously on day 1 of a 21-day cycle, typically for six cycles. Folate and vitamin B12 supplementation is mandatory and significantly reduces grade 3–4 hematologic toxicity.

== Where This Regimen Fits in 2026 ==

The 2020 FDA approval of '''nivolumab + ipilimumab''' (CheckMate 743) added an immunotherapy option to first-line treatment of unresectable pleural mesothelioma, with longer median overall survival than the historical Pem+Cis benchmark, particularly for non-epithelioid histology. The 2024 FDA approval of '''pembrolizumab + pemetrexed + platinum''' (KEYNOTE-483) further expanded the immunotherapy-based first-line landscape. Pemetrexed + cisplatin without immunotherapy remains a recognized regimen for patients with contraindications to checkpoint inhibition, performance status that precludes combination immunotherapy, or limited access to newer agents.

== References ==

<references />

== See Also ==

* [[Mesothelioma_Treatment]]
* [[Treatment_Options]]
* [[Pleural_Mesothelioma]]
* [[Clinical_Trials_Mesothelioma]]

[[Category:Treatment]]
[[Category:Chemotherapy]]
[[Category:Pleural_Mesothelioma]]