Single-arm, open label study of pemetrexed plus cisplatin in chemotherapy naïve patients with malignant pleural mesothelioma: Outcomes of an expanded access program

Lung Cancer. 2006 Nov 6. [Link]

Coleman K. Obasajua, Zhishen Yea, Antoinette J. Wozniakb, Chandra P. Belanic, Mary-Louise Keohand, Helen J. Rosse, Jonathan A. Polikofff, David M. Mintzerg, Matthew J. Monberga, Pasi A. Jänneh and On Behalf of Pemetrexed Expanded Access Program Investigators1

aEli Lilly and Company, Lilly Corporate Center, Drop Code 6831, Indianapolis, IN 46285, United States
bKarmanos Institute, Wayne State University, Detroit, MI, United States
cUniversity of Pittsburgh Cancer Institute, PA, United States
dColumbia-Presbyterian Medical Center, New York, NY, United States
eEarle A. Chiles Research Institute, Portland, OR, United States
fKaiser Hospital, San Diego, CA, United States
gPennsylvania Hospital, Philadelphia, PA, United States
hDepartment of Medical Oncology, Dana Farber Cancer Institute and Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United States

Received 5 July 2006;  revised 31 August 2006;  accepted 27 September 2006.  Available online 7 November 2006.


Background: An expanded access program (EAP) provided patient access to pemetrexed prior to its commercial availability. The current report consists of US patients in the EAP who had chemotherapy naïve pleural mesothelioma.

Methods: Eligible patients had a histologic or cytologic diagnosis of malignant mesothelioma that was not amenable to curative treatment with surgery. Study treatment consisted of pemetrexed 500 mg/m2 in combination with cisplatin 75 mg/m2 once every 21 days. Vitamin B12, folic acid, and dexamethasone were administered as prophylaxis. Serious adverse events (SAEs) were reported by investigators and compiled in a pharmacovigilance database for all patients enrolled in the EAP.

Results: Of 1056 patients receiving at least one dose of pemetrexed in the EAP, 728 had chemotherapy naïve pleural mesothelioma. Median age of this group was 70 years (range 23–89 years) and 84% were male. Among 615 patients, overall response rate was 20.5%, including 12 complete responses (2.0%) and 114 partial responses (18.5%). An additional 290 patients (47.2%) had stable disease. Median survival for all 728 patients was 10.8 months (95% CI = 9.8, 12.3; 60.3% censorship) and 1 year survival was 45.4%. The most commonly reported SAEs in the overall EAP irrespective of causality were dehydration (7.2%), nausea (5.2%), vomiting (4.9%), dyspnea (3.8%), and pulmonary embolism (2.4%).

Conclusions: In this large cohort, 67.7% of patients treated with first-line chemotherapy experienced a response or stable disease. Survival time and toxicity from this EAP were promising for this difficult-to-treat disease.

Keywords: Chemotherapy naïve; First-line; Malignant pleural mesothelioma; Pemetrexed; cisplatin; Expanded access program