Phase I trial of motexafin gadolinium in combination with docetaxel and cisplatin for the treatment of non-small cell lung cancer.

Abstract

INTRODUCTION:

Motexafin gadolinium is a novel antineoplastic drug that disrupts cancer cell antioxidant systems, thus contributing to cellular death. In patients with lung cancer, motexafin gadolinium has been shown to increase the time to neurologic progression when given in combination with whole-brain radiotherapy in randomized phase III studies. Preclinical data suggest that this drug might also enhance the antineoplastic effects of chemotherapy.

METHODS:

In this one-arm, open label, phase I, dose-escalation study, we administered docetaxel (75 mg/m2), cisplatin (75 mg/m2), and motexafin gadolinium every 3 weeks to patients with metastatic non-small cell lung cancer. Twenty-one patients were treated at one of four motexafin dose levels.

RESULTS:

The maximal tolerated motexafin dose was 10 mg/kg on day 1 of a 3-week cycle. Dose-limiting toxicities consisted of febrile neutropenia, hypertension, myocardial ischemia, and pneumonitis/pulmonary infiltrates. Other common grade 3-4 adverse events across all cohorts that did not appear to be exacerbated by motexafin gadolinium included granulocytopenia, fatigue, dehydration, nausea, and vomiting. Two episodes of myocardial ischemia and one sudden death of unknown cause were observed. Response rates were partial response (10%), stable disease (60%), and disease progression (30%).

CONCLUSIONS:

The regimen studied was tolerable and showed activity in patients with metastatic non-small cell lung cancer. The recommended doses for future phase II trials are motexafin gadolinium 10 mg/kg, docetaxel 75 mg/m2, and cisplatin 75 mg/m2 intravenously on day 1 every 3 weeks. Caution is advised in patients with a history of cardiovascular disease.

• Authors: William N William Jr, Ralph G Zinner, Daniel D Karp, Yun W Oh, Bonnie S Glisson, See-Chun Phan, David J Stewart
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 2 Issue 8 Pg. 745-50 (Aug 2007) ISSN: 1556-1380 [Electronic] United States
• PMID: 17762342 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Metalloporphyrins
• Taxoids
• Docetaxel
• motexafin gadolinium
• Cisplatin

Topics

• Adenocarcinoma (drug therapy, radiotherapy, secondary)
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology, radiotherapy)
• Carcinoma, Squamous Cell (drug therapy, radiotherapy, secondary)
• Cisplatin (administration & dosage)
• Docetaxel
• Dose-Response Relationship, Drug
• Female
• Humans
• Lung Neoplasms (drug therapy, pathology, radiotherapy)
• Male
• Maximum Tolerated Dose
• Metalloporphyrins (administration & dosage)
• Middle Aged
• Prognosis
• Survival Rate
• Taxoids (administration & dosage)