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Phase III Study of Matrix Metalloproteinase Inhibitor Prinomastat in Non–Small-Cell Lung Cancer

From the Aberdeen Royal Infirmary, Aberdeen; Leicester Royal Infirmary, Leicester; University of Edinburgh, Edinburgh, United Kingdom; Asklepios Fachkliniken, München-Gauting; Krankenhaus Grosshansdorf, Grosshansdorf, Germany; Marshfield Clinic, Marshfield, WI; Pfizer Global Research and Development, La Jolla, CA; and Princess Margaret Hospital, Toronto, Ontario, Canada

Address reprint requests to Donald Bissett, MD, Department of Clinical Oncology, Clinic D, Aberdeen Royal Infirmary, Aberdeen AB25 2ZN, United Kingdom; e-mail: d.bissett{at}arh.grampian.scot.nhs.uk

PURPOSE: Matrix metalloproteinases (MMPs) degrade extracellular proteins and facilitate tumor growth, invasion, metastasis, and angiogenesis. This trial was undertaken to determine the effect of prinomastat, an inhibitor of selected MMPs, on the survival of patients with advanced non–small-cell lung cancer (NSCLC), when given in combination with gemcitabine-cisplatin chemotherapy.

PATIENTS AND METHODS: Chemotherapy-naive patients were randomly assigned to receive prinomastat 15 mg or placebo twice daily orally continuously, in combination with gemcitabine 1,250 mg/m² days 1 and 8 plus cisplatin 75 mg/m² day 1, every 21 days for up to six cycles. The planned sample size was 420 patients.

RESULTS: Study results at an interim analysis and lack of efficacy in another phase III trial prompted early closure of this study. There were 362 patients randomized (181 on prinomastat and 181 on placebo). One hundred thirty-four patients had stage IIIB disease with T4 primary tumor, 193 had stage IV disease, and 34 had recurrent disease (one enrolled patient was ineligible with stage IIIA disease). Overall response rates for the two treatment arms were similar (27% for prinomastat v 26% for placebo; P = .81). There was no difference in overall survival or time to progression; for prinomastat versus placebo patients, the median overall survival times were 11.5 versus 10.8 months (P = .82), 1-year survival rates were 43% v 38% (P = .45), and progression-free survival times were 6.1 v 5.5 months (P = .11), respectively. The toxicities of prinomastat were arthralgia, stiffness, and joint swelling. Treatment interruption was required in 38% of prinomastat patients and 12% of placebo patients.

CONCLUSION: Prinomastat does not improve the outcome of chemotherapy in advanced NSCLC.

Supported by a project grant from Pfizer Pharmaceuticals.

Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 18-21, 2002.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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